Abstract
In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6–12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.
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Introduction
Multiple myeloma (MM) is a plasma cell neoplasm defined by the aberrant proliferation of clonal plasma cells. Infections are a significant cause of morbidity and death in patients with MM [1]. The overload of the monoclonal component comprised of defective immunoglobulin, together with decreased levels of normal immunoglobulin classes and defective cellular and innate immunity, leads to an inadequate host immune response to pathogens [2]. Patient-related factors including age, frailty and comorbidities may increase the susceptibility to infections [3, 4]. Furthermore, the current standard of anti-myeloma care includes drug combinations with significant hematological toxicity, such as neutropenia and lymphopenia. Patients treated with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) are at an increased risk of severe infections [5, 6]. Although CD38-directed monoclonal antibodies diminish immunosuppressive regulatory T cells, they also impair natural killer (NK) cells and increase susceptibility to viral and bacterial infections including atypical infections [7]. B-cell maturation antigen (BCMA)-directed therapies deplete the B-cell compartment, eliminate mature plasma cells, and impair humoral response to pathogens [8]. Long-term use of steroids, as well as autologous stem cell transplantation (ASCT), are also associated with substantial immunosuppression [9].
Coronavirus disease 2019 (COVID-19) pandemic had a substantial impact on the management of patients with MM [10, 11], as they are at increased risk for severe COVID-19 and adverse outcomes [12]. Although treatment administration is no longer modified and vaccination is widely used, patients with MM present a substantial risk for breakthrough infections [13].
Currently, the dominant SARS-CoV-2 variants are more transmissible than previous strains but produce usually mild or asymptomatic COVID-19 in otherwise healthy, vaccinated individuals. At the same time, restrictions, related to SARS-CoV-2 preventive measures, have been lifted in the western countries. As we enter the post pandemic era and SARS-CoV-2 becomes endemic, the European Myeloma Network (EMN) aimed to provide updated directions for the management of patients with MM and COVID-19 (Table 1).
Methodology
In October 2022, a panel of experts of the EMN convened to develop updated consensus on the management of COVID-19 in MM patients. After a comprehensive review of the literature (PubMed, MM meetings and EMN consortia) from January 2020 to March 2023, a preliminary draft of the manuscript was distributed to all members of the group, who were invited to comment on the proposed manuscript draft and make suggestions. After the first manuscript proposal, further rounds of reviews and amendments, a final paper version was produced and approved by all authors.
COVID-19 in MM patients; prognostic factors and role of SARS-CoV-2 variants
Since 2019, SARS-CoV-2 infection appeared as a clinically heterogeneous disorder, ranging from a completely asymptomatic phase to mild or moderate respiratory symptoms, up to severe pneumonia, respiratory distress syndrome, multiorgan failure and death [14, 15]. Extra-pulmonary manifestations and various types of long-term complications were also subsequently recognized [16,17,18,19]. Patients with MM or other hematology malignancies (HM) are at high risk for severe COVID-19, compared to the general (healthy and non-cancer) population [20, 21] and possibly also to other cancer patients [22,23,24]. They may develop acute respiratory distress syndrome (ARDS) and thrombotic complications that can induce high in-hospital mortality [25]. This is due to MM patients’ advanced age, co-existing medical conditions, as well as to humoral and cellular immunity compromised by the disease itself and by concomitant, often prolonged-applied targeted and immunosuppressive therapies, including steroids, monoclonal antibodies [26, 27], ASCT [28], and novel cellular therapies [29, 30]. Furthermore, MM patients often show low/suboptimal rates (in terms of percentage of responders and magnitude of response) of both humoral and functional T-cell immune responses to anti-SARS-CoV-2 vaccines [31,32,33,34]; this further contributes to an increased risk of severe COVID-19, need of hospitalization and higher mortality rates [35]. Notably, an appropriate use of one [36,37,38,39,40] or two [41, 42] “booster” doses may significantly improve vaccine performance, particularly among patients who failed to respond to the initial two doses with mRNA vaccines. However, several of these patients may still have vaccine failure due to severe immune impairment, particularly those who receive anti-BCMA treatments [39, 41].
It has been recently reported that the expression of angiogenic factors and glutamine deficiency could link COVID-19 severity and MM in the pathogenesis of thrombotic and other cardiovascular complications [43]. Furthermore, a longer time to respiratory deterioration after SARS-CoV-2 infection, compared to non-hematological subjects, also predicts mortality in MM patients, which suggests that prolonged clinical monitoring may be needed [44]. Finally, whilst SARS-CoV-2 infection may exacerbate the development of acute kidney injury and neurological complications in MM patients, the occurrence of secondary infections has also been associated with poor COVID-19 outcome [45].
Several papers have addressed the outcome of COVID-19 in MM patients, during the first waves of pandemic, sustained by SARS-CoV-2 ancestral Wuhan strain (WA1), alpha (B.1.1.7) and delta (B.1.617.2) variants (all currently considered “de-escalated” variants) in the pre-vaccination era, before December 2020 (Table 2) [11, 12, 21, 46,47,48,49,50,51,52].
Looking specifically at the data collected after the start of vaccination (grossly from December 2020), Ho et al. [4] reviewed the medical records of 174 MM patients with COVID-19 infection seen at Mayo Clinic between December 2019, and August 2021. The infection rate in this cohort was relatively low (2% among 9225 patients with MM or AL-amyloidosis), but one-fourth of the COVID-19 infections were severe. Nineteen (10%) patients required ICU admission and 5 (3%) patients needed mechanical ventilation. The mortality rate among hospitalized patients with COVID-19 was 22% (16/72 patients). On multivariate analysis, treatment with CD38 antibody within 6 months of COVID-19 infection, and cardiac or pulmonary comorbidities were independent predictors for ICU admission. Cardiac comorbidity [RR 2.6 (95% CI: 1.1, 6.5), p = 0.038] was an independent predictor of mortality, whereas unsurprisingly, achieving MM-remission was associated with lower mortality [RR 0.4 (95% CI: 0.2–0.8); p = 0.008].
On 26 November 2021, the WHO declared the Omicron variant (B.1.1.529) of SARS-CoV-2, as a new variant of concern (VOC), while since January 2022, BA.2.12.1, BA.4, BA.5, BQ.1.1, and XBB.1 Omicron VOC new sub-variants, all exhibiting higher transmissibility than the BA.2, have become largely prevalent. In addition, the BQ.1.1 and XBB.1 variants are now dominant in Europe and the US. The newly emerged Omicron variants of SARS-CoV-2 harbor multiple novel spike protein mutations that raise concerns about clinical outcome of COVID-19 in MM patients infected by these variants, vaccine efficiency and antiviral efficacy of the available therapeutic monoclonal antibodies. In fact, a recent publication shows the lowest vaccine-elicited neutralisation activity against BA.2.75.2, BQ.1.1, and XBB.1 [53].
The EPICOVIDEHA registry recently updated the outcome of 1221 MM patients with COVID-19 collected between February, 2020 and August, 2022 [54]. At the time of analysis, 414 patients (34%) were vaccinated with one or more doses (mainly with three). Of note, 446 patients (36.5%) were managed as outpatients during SARS-CoV-2 infection, while 775 patients (63.5%) were hospitalized. Over 10%, namely 13.8% (n = 169) of patients were admitted to an ICU and 63.3% of them required invasive mechanical ventilation. In 346 (28.3%) patients, specific treatments were reported, including various combinations of antivirals, monoclonal antibodies, corticosteroids and convalescent plasma. With a median follow-up of 52 days for the entire cohort and 83.5 days for survivors, 303 patients died (total mortality rate: 25%). The reported primary reason for death was COVID-19 or a combination of MM and COVID-19 in approximately 90% of patients. OS was significantly higher in vaccinated patients with both stable and active MM versus not vaccinated ones (p = 0.002 and p = 0.003, respectively). At multivariate analysis, age, renal failure, active disease, hospital stay and ICU admission were independently associated with poor survival. Notably, a time-dependent analysis revealed that mortality rates progressively and significantly declined throughout the different pandemic waves, from 34% (first wave) to 10.2% (last wave), likely reflecting, along with the already demonstrated usefulness of other general measures, the efficacy of extensive vaccination policies even against new emerging variants of concern, such as BA.2, BA.4, BA.5, B.Q.1.1, and XBB.1.
Another study from the EPICOVIDEHA registry was the first report on clinical data in a large cohort of exclusively Omicron-infected HM patients [55]. In total, 593 HM patients (including 97 MM) infected with documented Omicron VOC starting from June 2021 were analyzed. Overall mortality among hospitalized patients, was 16.5% (51/309), 95.4% of whom was classified as attributable to or contributable by Omicron. Risk factors associated with mortality in hospitalized patients were older age (HR 1.05 [95% CI] 1.02–1.07, p < 0.001]) and active malignancy (HR 2.5 [95% CI 1.3–4.8, p = 0.007]). Progression to critical infection occurred in 53 (17.0%) of hospitalized patients. A risk factor for progression to critical COVID-19 was pre-existent chronic pulmonary disease (OR 3.2 [95% CI 1.4–7.3, p = 0.005]). Baseline lymphocytes of ≥500 cells/mm3 (OR 0.4 [95% CI 0.18–0.90, p = 0.027]) and three doses of vaccine were protective (OR 0.29 [95% CI 0.13–0.64, p = 0.003]). Mortality among patients with critical infection was 39.2% (20/53).
The update of EPICOVIDEHA registry showed that the mortality rate in patients with Omicron variants was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the pre-vaccine era (31%). In the multivariable model, older age, active disease, severe COVID-19, and 2–3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration against SARS-CoV-2, alone or combined with antivirals, was protective [54,55,56].
COVID-19 vaccine effectiveness in patients with MM
The most important strategy to fight COVID-19 is vaccination. The authorized vaccines employ a variety of platforms including mRNA, viral vectors, proteins/peptides, and inactivated viruses. Despite that robust clinical data with direct comparisons among the available vaccines are not available, preclinical results indicate that antibody responses to mRNA vaccines and the Novavax protein subunit vaccine are greater than those to viral-vectored and inactivated virus vaccines [57]. mRNA-based vaccines against SARS-CoV-2 are currently the mainstay of COVID-19 vaccination strategies in Europe and in the USA including booster vaccinations, preferably with the adapted bivalent vaccines [58].
Vaccine effectiveness in the real-world depends on several factors including demographic and host characteristics (age, comorbidities, previous COVID-19 infection, herd immunity), immune factors (humoral and T-cell response to vaccination, immune compromise, immunological disease), viral characteristics (antigenic shift, transmissibility, new variants) and factors related to vaccine access including vaccine type, number of doses and time interval between doses, vaccine availability [56]. In patients with MM, reduced vaccine response is caused by myeloma- and treatment-related immune deregulation, but it is further impacted by advanced age and comorbidities [31, 59]. Although novel SARS-CoV-2 variants are more transmissible than previous strains and they may compromise vaccine effectiveness, booster vaccination is effective against symptomatic infection from the Omicron variants. However, vaccine effectiveness wanes over time [60].
An emerging question, after the application of large vaccination campaigns and the appearance of novel virus mutants, is the incidence and the clinical outcome of breakthrough SARS-CoV-2 infection in vaccinated patients. In this setting, the National COVID Cohort Collaborative program provided real-world evidence on risks and outcomes of breakthrough SARS-CoV-2 infections in vaccinated patients with cancer [13]. A total of 1460 breakthrough cases within cancer patients partially or fully vaccinated with mRNA COVID-19 vaccines and no prior SARS-CoV-2 infection were recorded between December 2020 and May 2021. Solid tumors and HM had significantly higher risks for breakthrough infection (ORs = 1.12, 95% CI, 1.01 to 1.23 and 4.64, 95% CI, 3.98 to 5.38) and severe outcomes (ORs = 1.33, 95% CI, 1.09 to 1.62 and 1.45, 95% CI, 1.08 to 1.95) compared with non-cancer patients, adjusting for age, gender, race/ethnicity, smoking status, vaccine type, and vaccination date. In comparison with solid tumors, HM were at increased risk for breakthrough infections. Non-surprisingly, breakthrough risk was reduced after the second vaccine dose for all cancers (OR = 0.04; 95% CI, 0.04 to 0.05), and for Moderna’s mRNA-1273 compared with Pfizer’s BNT162b2 vaccine (OR = 0.66; 95% CI, 0.62 to 0.70), particularly in patients with MM (OR = 0.35; 95% CI, 0.15 to 0.72). Medications with major immunosuppressive effects and stem cell transplantation were strongly associated with increased breakthrough risk among the vaccinated population.
Literature data have shown that patients with MM are more likely to have breakthrough infections (13–15%) compared to non-cancer patients (~4%), and that these infections are linked to an increased risk of hospitalization along with significant morbidity and mortality [61,62,63]. Overall, older patients and those with common and significant comorbidities, as well as patients who received chemotherapy or targeted therapies, were more vulnerable to breakthrough infection [64].
The results of a recent cross-sectional study, including 3555 patients with cancer and 225,272 individuals without cancer, showed that the humoral response following COVID-19 vaccination may enable the identification of vulnerable patients. Patients with suboptimal levels of anti-spike SARS-CoV-2 antibodies had an increased risk for breakthrough COVID-19 infections and hospitalization due to COVID-19 [65]. Taking into consideration that studies addressing the clinical effectiveness of COVID-19 vaccines in patients with MM are rather limited, we may infer protection against COVID-19 by evaluating the kinetics of humoral response following vaccination [66, 67]. We should also consider that the presence of anti-SARS-CoV-2 spike receptor-binding domain (RBD) antibodies does not always correlate with the presence of neutralizing antibodies against SARS-CoV-2. Up to one third of vaccinated MM patients with two doses of mRNA-based vaccines, who have detectable anti-spike RBD antibodies, do not present neutralizing activity against SARS-CoV-2 [68]. Neutralizing antibody levels predict immunological protection against symptomatic SARS-CoV-2 infection [69, 70].
Several studies have evaluated the immune response following the prime complete COVID-19 vaccination in patients with MM [68, 71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110]. Three large meta-analyses have summarized the findings of these studies [32, 33, 111]. Gagelmann et al included data on 1564 patients from 13 studies and showed a pooled antibody response of 76% (95% CI: 67–83%) with significant heterogeneity (I² = 91%) [33]. The results were consistent with the meta-analysis by Ito et al, who performed a subgroup analysis on 15 studies with data on MM and found a pooled seropositivity rate of 78% (95% CI: 69%-86%) with significant heterogeneity (I² = 92%) [111]. Expectedly, patients with smoldering MM (SMM; 5 studies), similarly as presumed for MGUS patients, showed a high pooled seroconversion rate of 94% (95% CI: 76–100%; I² = 87%), which was not statistically different from healthy individuals (random effects RR 0.96, 95% CI: 0.75–1.24) [111]. Active treatment with CD38-targeting drugs was associated with inferior humoral responses compared to other therapeutic combinations (random effects RR 0.86, 95% CI: 0.76–0.96) [111]. Overall, the neutralizing antibody response rate was 62.7% (range 53.3–68.6%) after two doses of mRNA SARS-CoV-2 vaccines. Patients who did not receive any treatment at the time of vaccination were more likely to seroconvert with a pooled odds ratio (OR) of 2.42 (95% CI: 1.10–5.33, low heterogeneity I2 = 7%). Patients on active treatment with anti-CD38 monoclonal antibodies had inferior humoral responses (pooled OR 0.42, 95% CI: 0.22–0.79, I2 = 14%) against the Wuhan strain but also against the Alpha and Delta SARS-CoV-2 variants [68, 90]. Patients who were vaccinated more than 30 days from the last anti-CD38 drug infusion seem to have enhanced humoral responses [94]. A longer time interval of 3 months from the last treatment dose to vaccination may further enhance seroconversion rates [112]. Patients with high-risk cytogenetics were also less likely to respond to vaccination (pooled OR of two studies 0.36, 95% CI: 0.18–0.69, I2 = 0%) [32].
Studies have also reported that older age, lymphopenia and active treatment with BCMA-targeting agents are associated with low rates of antibody response following prime two-dose COVID-19 vaccination [71, 72, 74, 76,77,78, 81, 86, 88, 89, 94, 96]. Recent ASCT does not seem to impair humoral responses to COVID-19 vaccination, thus most SCT-center recommend re-boosters post ASCT [84, 100, 107, 108]. Furthermore, mRNA1273 seems to induce greater neutralizing antibody responses compared with BNT162b2 in patients with MM [68].
Humoral immunity against SARS-CoV-2 declines over time and, thus, booster vaccination with mRNA-based vaccines has been implemented at 6 months following the completion of the prime vaccination. Terpos et al showed that booster vaccination significantly improves neutralizing antibody response against the Wuhan strain of SARS-CoV-2 with a median neutralization activity of 96.7% (interquartile range 52.6–97.8%) in a prospective study on 167 patients with symptomatic MM [39]. Importantly, almost half of the non-responders after the initial vaccination did respond following the booster vaccine shot. Of course, responders to complete vaccination were more likely to mount robust antibody responses to booster vaccination. A third vaccine shot may also overcome the negative effect of anti-CD38 treatment, but not that of anti-BCMA agents [39]. Furthermore, a booster shot with mRNA-1273 may induce more robust antibody responses compared with the BNT162b2 booster [36].
Aleman et al. evaluated the immune response to booster vaccination in 261 patients with MM [113]. The booster vaccine shot (BNT162b2 or mRNA-1273) significantly increased the anti-spike RBD antibodies, including patients with antibody levels below the positivity threshold before the administration of the third dose, which is in line with other studies [36,37,38, 113,114,115,116,117,118]. Enssle et al. evaluated the neutralizing activity against SARS-CoV-2 variants in 100 patients with MM; the booster shot led to sufficient neutralization titers against Delta and Omicron in 64% and 29% of the patients, respectively [118]. Azeem et al. also reported that the third vaccine shot increased the neutralizing antibodies against Omicron in only one third of 187 patients with MM [119]. Breakthrough COVID-19 infections post booster were documented in 24 patients (13%), who also had lower neutralization titers against Omicron subvariants compared with the others [119].
Patients with relapsed/refractory disease (RRMM) may show attenuated neutralizing responses against Omicron even after the third vaccine shot, in comparison to newly-diagnosed patients who show an increase in neutralizing titers against both the Wuhan strain and variants of concern (Omicron, Delta, Gamma, Beta, Alpha) [120]. Active treatment, especially with B-cell depleting drugs, at the time of booster vaccination seems to have an adverse impact on the neutralizing activity against immunologically divergent SARS-CoV-2 variants, such as the Omicron BA.4/5 [121]. The levels of anti-spike antibodies have been correlated with neutralization capacity against Omicron; however, particularly higher levels were necessary to reach the neutralization threshold against Omicron as compared with Delta and Wuhan [113, 118, 121].
Furthermore, Ntanasis-Stathopoulos et al. evaluated the neutralizing humoral response against the ancestral strain of SARS-CoV-2 after the second booster vaccination (fourth vaccine dose against the initial Wuhan strain) in 201 patients with MM [41]. The fourth dose was administered 6 months after the third vaccine and restored the neutralizing activity against the Wuhan strain to the levels achieved after the first booster (median 96%). Although treatment with anti-CD38 did not impair humoral responses post second booster, anti-BCMA targeted therapy, with belantamab mafodotin, remained a negative predictive factor for antibody response [41]. Faustini et al. confirmed that multiple booster vaccine doses can provide effective protection from COVID-19, even with intensive anti-CD38 therapy for high-risk MM [122].
In addition, patients with MM present defective cellular responses to COVID-19 vaccination. Studies have shown that the initial two-dose vaccination scheme results in reduced levels of SARS-CoV-2-specific CD4 + T-cells, but not CD8 + T-cells, compared with healthy individuals [123]. A pooled analysis of three studies has shown that, on average, the rate of positive functional T-lymphocyte response was 44.2% (34.2–48.5%) after two doses of mRNA-based SARS-CoV-2 vaccines [32]. Following booster vaccination, patients with MM show remarkable CD4 + T cell-mediated cytokine responses against the Wuhan, Delta and Omicron strains [113, 118,119,120]. Spike-specific CD8 + T-cell responses to booster vaccination are more variable and may depend on the immune status of each patient [120]. Type of treatment at the time of vaccination seems to exert an important effect on cellular responses. Patients receiving anti-CD38 monoclonal antibodies or anti-BCMA bispecific T-cell engagers showed inferior CD4 +T-cell responses against SARS-CoV-2 compared with other therapeutic agents [99, 124]. Interestingly, a subset of patients on anti-CD38 directed treatments may present a delayed antibody response, which has been correlated with low counts of regulatory T-cells [125]. T-cell responses against SARS-CoV-2 variants of concern may be important to attenuate the disease severity in breakthrough infections [126]. Another point to consider is that spike-specific T-cell responses may become evident even in seronegative patients following vaccination [97, 119, 127], which underlines the importance of booster vaccination for supporting cellular immunity in these patients.
Moreover, recent studies have suggested that hybrid immunity, following recovery from earlier Omicron SARS-CoV-2 subvariants and vaccination, may be more protective against infection from novel subvariants compared to vaccination-only immunity [128]. The breadth of immune response against SARS-CoV-2 variants is also wider following infection than after vaccination [129]. Studies have shown mixed results regarding the serological response following COVID-19 in patients with plasma cell dyscrasias [130, 131]. Interestingly, SARS-CoV-2 infection may induce superior humoral responses compared to the initial two-dose vaccination scheme in patients with MM on active treatment [132]. Patients who had been infected with SARS-CoV-2 prior to COVID-19 immunization showed more robust antibody responses than COVID-19-naive patients [71]. Recovery from COVID-19 before the booster dose was also associated with enhanced humoral responses [118]. Therefore, hybrid immunity is important in patients with MM and those who have recovered from COVID-19 should follow the recommendations for booster vaccinations [133].
Last but not least, seasonal influenza has returned to the foreground and may lead to severe respiratory disease, especially in immunocompromised patients including those with MM. Tandem high-dose influenza vaccination separated by 30 days leads to higher serologic hemagglutinin inhibition titer responses and more durable influenza-specific immunity in patients with plasma cell dyscrasias compared to single-dose standard-of-care vaccination [134]. Therefore, two doses of flu vaccines separated by one month are recommended for patients with MM. Simultaneous administration of COVID-19 and influenza vaccines is feasible [9].
Pre- and post-exposure prophylaxis for COVID-19
Vaccination and everyday preventive measures against SARS-CoV-2 are the cornerstones of preventing COVID-19. Pre-exposure prophylaxis with monoclonal antibodies targeting SARS-CoV-2 has been found effective especially in the pre-Omicron era [135].
The emergence and dominance of new SARS-CoV-2 Omicron subvariants such as XBB and XBB.1.5 raises severe concerns on the neutralizing ability of tixagevimab/cilgavimab against these subvariants [136]. Due to lack of activity against the new omicron variants, the monoclonal antibodies tixagevimab/cilgavimab, sotrovimab and bebtelovimab are no longer authorized for clinical use by the FDA and EMA.
Immunoglobulin administration, either as IVIG or as subcutaneous IG, is not a SARS-CoV-2-specific treatment. It could be considered in patients with multiple episodes of recurrent/persistent infections and low IgG levels less than 400 mg/ml [9].
Treatment of patients with MM and COVID-19
The administration of oral antivirals including nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio) in outpatients with COVID-19 and high risk for severe disease has improved patient outcomes in terms of hospitalization and death at 1 month [137, 138]. They should be administered as soon as possible after the positive SARS-CoV-2 test and within 5 days post symptoms onset.
However, a recent analysis of the PANORAMIC trial in the UK showed that the addition of molnupiravir in the standard care of patients with COVID-19 during the first 5 days did not improve patient outcomes in terms of hospitalization and death due to COVID-19, although a statistical non-significant tendency for shorter time to recovery was noted in the molnupiravir exposed group. More than 90% of the patients had received at least three vaccine shots and all of them had increased risk of severe outcomes [139]. A recent study showed that the risk of viral rebound after receiving oral antivirals is small and it is not associated with excess mortality [140]. In vitro studies have shown that nirmatrelvir/ritonavir and molnupiravir remain effective against Omicron subvariants BA.2.12.1, BA.4, and BA.5, while nirmatrelvir/ritonavir is also effective against XBB and XBB.1.5 [141, 142].
A prospective study evaluated the efficacy and safety of oral antivirals in 169 patients with MM and COVID-19 [143]. All patients had received three doses of mRNA-based vaccines and were diagnosed with COVID-19 during the initial Omicron waves (first half of 2022). A total of 139 patients was treated with ritonavir-nirmatrelvir, while the remaining 30 patients were treated with molnupiravir. In total, 149 patients (88.2%) had a mild infection, 15 (8.9%) had moderate infection, and five (3%) had severe COVID-19. No differences in the severity of COVID-19-related outcomes were observed between the two antivirals. Patients with severe disease had lower neutralizing antibody levels before the COVID-19 infection compared to patients with mild disease (p = 0.04). Regarding treatment, it was observed that patients receiving belantamab mafodotin had a higher risk of severe COVID-19 (p < 0.001) [143]. Similar results have been reported in a case series of 15 patients with MM and COVID-19 who received antivirals [144].
However, it is known that almost 15% of patients cannot receive ritonavir-nirmatrelvir due to their concomitant medication. In this case, remdesivir is recommended; it is administered either in the outpatient setting for 3 consecutive days starting within 7 days of symptoms onset or in the inpatient setting for 5 consecutive days [145, 146]. Preclinical data have shown that remdesivir remains effective against Omicron subvariants, including XBB and XBB.1.5 [141]. However, Remdesivir usage is limited in patients with severe chronic kidney failure.
COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies is authorized for the treatment of COVID-19 in patients with immunosuppressive disease such as MM or those receiving immunosuppressive treatment in inpatient or outpatient settings [147, 148]. Patient selection and time of convalescent plasma administration are important factors to consider [149]. However, there are no studies for the use of convalescent plasma in MM patients, especially in the era of Omicron subvariants, and thus the use of convalescent plasma is not recommended for use in MM patients.
Taking into consideration that most symptomatic COVID-19 infections last for less than 10 days, MM therapy may be postponed for 7 to 10 days from COVID-19 diagnosis, similar to the management of other infections [3]. Severe and complicated COVID-19 cases may necessitate longer treatment interruptions, prolonged hospitalization and intensive care [150].
Conclusions
MM patients are at high risk of severe COVID-19 and related mortality in the post-pandemic era; this risk is reduced compared to the initial Wuhan and Delta strains. According to different studies, risk factors for poor survival after COVID-19 in MM include older age, male sex, uncontrolled/active and/or high-risk disease, multiple comorbidities (mainly cardio-vascular, pulmonary and renal), inflammatory response, race/ethnicity, severe/critical COVID-19, ICU stay, lymphocyte count, vaccination status and recent systemic anticancer therapies (especially targeting BCMA). At least some of these parameters seem to have reduced their importance after the start of vaccination era (i.e. racial or ethnic disparities).
The rapid appearance of new and more diffusive viral mutants has maintained the incidence of COVID-19, although its poor clinical outcome appears to be mitigated. However, there are specific MM populations (i.e. those who receive anti-BCMA therapies) who remain minutely responsive to vaccines and at risk of severe and potentially life-threatening breakthrough infections. These data confirm the possible immune-escape of at least some Omicron variants and thus support calls for rapid approval of second-generation vaccines adapted to both the initial strains, but also to novel SARS-CoV-2 dominant mutants.
Currently available recommendations and detailed decision-making algorithms for the management of patients with MM during COVID-19 pandemic remain based on consensus and are lesser “evidence based”, although important information have been implemented during the last three years (Table 1). Therefore, advocacy to include immune-compromised people in pivotal vaccine trials, in prospective cohort studies, and an effort to systematically test strategies to boost vaccine response will help to protect patients with HM (including MM) against COVID-19 and future outbreaks.
On the other hand, preventive measure must be strictly continued, even in the vaccination (and post-vaccination) phases, to maintain virus mitigation strategies in MM patients. MM patients should be vaccinated with an updated booster, preferably mRNA-based, omicron-adapted vaccines such as the Spikevax bivalent Original/Omicron BA.4–5 or the Comirnaty Original/Omicron BA.4–5, either in a treatment-free interval or when deep remission is achieved. Novel monoclonal antibodies targeting the novel SARS-CoV-2 variants for prophylactic use are highly anticipated by the MM community. In case of COVID-19 infection, MM patients should be offered oral antivirals or remdesivir, since they remain effective against Omicron subvariants.
New possibilities, such as the use of artificial neural networks (ANN) based on simple laboratory indices [151] are promising in order to generate useful models to predict the clinical outcome of COVID-19 and these methods could be applied to MM patients in the near future.
Data availability
No data to deposit in a repository; further data available upon request from the corresponding author.
References
Blimark C, Holmberg E, Mellqvist UH, Landgren O, Bjorkholm M, Hultcrantz M, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100:107–13.
Sorrig R, Klausen TW, Salomo M, Vangsted A, Gimsing P. Risk factors for infections in newly diagnosed multiple myeloma patients: a Danish retrospective nationwide cohort study. Eur J Haematol. 2019;102:182–90.
Raje NS, Anaissie E, Kumar SK, Lonial S, Martin T, Gertz MA, et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 2022;9:e143–61.
Ho M, Zanwar S, Buadi FK, Ailawadhi S, Larsen J, Bergsagel L, et al. Risk factors for severe infection and mortality In patients with COVID-19 in patients with multiple myeloma and AL amyloidosis. Am J Hematol. 2023;98:49–55.
Chen M, Zhao Y, Xu C, Wang X, Zhang X, Mao B. Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies. Ann Hematol. 2018;97:925–44.
Basler M, Lauer C, Beck U, Groettrup M. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. J Immunol. 2009;183:6145–50.
Nahi H, Chrobok M, Gran C, Lund J, Gruber A, Gahrton G, et al. Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma. PLoS One. 2019;14:e0211927.
Zhou D, Wang Y, Cheng H, Zhu L, Chen W, Li H, et al. Factors associated with infection events after chimeric antigen receptor T-cell therapy for relapsed or refractory multiple myeloma. J Infect Chemother. 2023;29:179–85.
Ludwig H, Boccadoro M, Moreau P, San-Miguel J, Cavo M, Pawlyn C, et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2021;35:31–44.
Terpos E, Engelhardt M, Cook G, Gay F, Mateos MV, Ntanasis-Stathopoulos I, et al. Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN). Leukemia. 2020;34:2000–11.
Martinez-Lopez J, Hernandez-Ibarburu G, Alonso R, Sanchez-Pina JM, Zamanillo I, Lopez-Munoz N, et al. Impact of COVID-19 in patients with multiple myeloma based on a global data network. Blood Cancer J. 2021;11:198.
Pagano L, Salmanton-Garcia J, Marchesi F, Busca A, Corradini P, Hoenigl M, et al. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA). J Hematol Oncol. 2021;14:168.
Song Q, Bates B, Shao YR, Hsu FC, Liu F, Madhira V, et al. Risk and outcome of breakthrough COVID-19 infections in vaccinated patients with cancer: real-world evidence from the national COVID cohort collaborative. J Clin Oncol. 2022;40:1414–27.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl J Med. 2020;382:1708–20.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
Yousif E, Premraj S. A review of long COVID with a special focus on its cardiovascular manifestations. Cureus. 2022;14:e31933.
Patel UK, Mehta N, Patel A, Patel N, Ortiz JF, Khurana M, et al. Long-term neurological sequelae among severe COVID-19 patients: a systematic review and meta-analysis. Cureus. 2022;14:e29694.
Korompoki E, Gavriatopoulou M, Hicklen RS, Ntanasis-Stathopoulos I, Kastritis E, Fotiou D, et al. Epidemiology and organ specific sequelae of post-acute COVID19: a narrative review. J Infect. 2021;83:1–16.
Korompoki E, Gavriatopoulou M, Fotiou D, Ntanasis-Stathopoulos I, Dimopoulos MA, Terpos E. Late-onset hematological complications post COVID-19: an emerging medical problem for the hematologist. Am J Hematol. 2022;97:119–28.
Vijenthira A, Gong IY, Fox TA, Booth S, Cook G, Fattizzo B, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020;136:2881–92.
Passamonti F, Cattaneo C, Arcaini L, Bruna R, Cavo M, Merli F, et al. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020;7:e737–45.
Kuderer NM, Choueiri TK, Shah DP, Shyr Y, Rubinstein SM, Rivera DR, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395:1907–18.
Lee LYW, Cazier JB, Starkey T, Briggs SEW, Arnold R, Bisht V, et al. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study. Lancet Oncol. 2020;21:1309–16.
Dai M, Liu D, Liu M, Zhou F, Li G, Chen Z, et al. Patients with cancer appear more vulnerable to SARS-CoV-2: a multicenter study during the COVID-19 outbreak. Cancer Disco. 2020;10:783–91.
Fernandez-Cruz A, Puyuelo A, Nunez Martin-Buitrago L, Sanchez-Chica E, Diaz-Pedroche C, Ayala R, et al. Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: an age-matched cohorts study. Clin Infect Pr. 2022;13:100137.
Girmenia C, Cavo M, Corso A, Di Raimondo F, Musto P, Offidani M, et al. Management of infectious risk of daratumumab therapy in multiple myeloma: a consensus-based position paper from an ad hoc Italian expert panel. Crit Rev Oncol Hematol. 2022;172:103623.
Cipkar C, Chen C, Trudel S. Antibodies and bispecifics for multiple myeloma: effective effector therapy. Hematol Am Soc Hematol Educ Program. 2022;2022:163–72.
Sharma A, Bhatt NS, St Martin A, Abid MB, Bloomquist J, Chemaly RF, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. Lancet Haematol. 2021;8:e185–93.
Hansen DK, Sidana S, Peres LC, Colin Leitzinger C, Shune L, Shrewsbury A, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol. 2023;41:2087–97.
Rodriguez-Otero P, San-Miguel JF. Cellular therapy for multiple myeloma: what’s now and what’s next. Hematol Am Soc Hematol Educ Program. 2022;2022:180–9.
Ludwig H, Sonneveld P, Facon T, San-Miguel J, Avet-Loiseau H, Mohty M, et al. COVID-19 vaccination in patients with multiple myeloma: a consensus of the European Myeloma Network. Lancet Haematol. 2021;8:e934–46.
Chuleerarux N, Manothummetha K, Moonla C, Sanguankeo A, Kates OS, Hirankarn N, et al. Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis. Blood Adv. 2022;6:6198–207.
Gagelmann N, Passamonti F, Wolschke C, Massoud R, Niederwieser C, Adjalle R, et al. Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. Haematologica. 2022;107:1840–9.
Wang X, Sima L. Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis. J Infect. 2022;S0163-4453(22)00674-0. https://doi.org/10.1016/j.jinf.2022.11.013.
Mittelman M, Magen O, Barda N, Dagan N, Oster HS, Leader A, et al. Effectiveness of the BNT162b2mRNA COVID-19 vaccine in patients with hematological neoplasms in a nationwide mass vaccination setting. Blood. 2022;139:1439–51.
Goldwater MS, Stampfer SD, Sean Regidor B, Bujarski S, Jew S, Chen H, et al. Third dose of an mRNA COVID-19 vaccine for patients with multiple myeloma. Clin Infect Pr. 2023;17:100214.
Haggenburg S, Hofsink Q, Lissenberg-Witte BI, Broers AEC, van Doesum JA, van Binnendijk RS, et al. Antibody response in immunocompromised patients with hematologic cancers who received a 3-dose mRNA-1273 vaccination schedule for COVID-19. JAMA Oncol. 2022;8:1477–83.
Re D, Seitz-Polski B, Brglez V, Carles M, Graca D, Benzaken S, et al. Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies. Nat Commun. 2022;13:864.
Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, Malandrakis P, et al. Booster BNT162b2 optimizes SARS-CoV-2 humoral response in patients with myeloma: the negative effect of anti-BCMA therapy. Blood. 2022;139:1409–12.
Attolico I, Tarantini F, Carluccio P, Musto P. Serological response following anti-SARS-CoV-2 vaccination in hematopoietic stem cell transplantation patients depends upon time from transplant, type of transplant and “booster” dose. Haematologica. 2022;107:1218.
Ntanasis-Stathopoulos I, Karalis V, Gavriatopoulou M, Malandrakis P, Sklirou AD, Eleutherakis-Papaiakovou E, et al. Second booster BNT162b2 restores SARS-CoV-2 humoral response in patients with multiple myeloma, excluding those under anti-BCMA therapy. Hemasphere. 2022;6:e764.
Salmanton-Garcia J, Marchesi F, Glenthoj A, Bilgin YM, van Praet J, Davila-Valls J, et al. Improved clinical outcome of COVID-19 in hematologic malignancy patients receiving a fourth dose of anti-SARS-CoV-2 vaccine: an EPICOVIDEHA report. Hemasphere. 2022;6:e789.
Al-Kuraishy HM, Al-Gareeb AI, Mohammed AA, Alexiou A, Papadakis M, Batiha GE. The potential link between Covid-19 and multiple myeloma: a new saga. Immun Inflamm Dis. 2022;10:e701.
Oliva A, Curtolo A, Volpicelli L, Cancelli F, Borrazzo C, Cogliati Dezza F, et al. Clinical course of Coronavirus Disease-19 in patients with haematological malignancies is characterized by a longer time to respiratory deterioration compared to non-haematological ones: results from a case-control study. Infection. 2022;50:1373–82.
Zappasodi P, Cattaneo C, Valeria Ferretti V, Mina R, Jose Maria Ferreri A, Merli F, et al. Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: a report from the ITA-HEMA-COV. Hematol Oncol. 2022;40:846–56.
Wang B, Van Oekelen O, Mouhieddine TH, Del Valle DM, Richter J, Cho HJ, et al. A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward. J Hematol Oncol. 2020;13:94.
Hultcrantz M, Richter J, Rosenbaum CA, Patel D, Smith EL, Korde N, et al. COVID-19 infections and clinical outcomes in patients with multiple myeloma in New York City: a cohort study from five academic centers. Blood Cancer Disco. 2020;1:234–43.
Engelhardt M, Shoumariyeh K, Rosner A, Ihorst G, Biavasco F, Meckel K, et al. Clinical characteristics and outcome of multiple myeloma patients with concomitant COVID-19 at Comprehensive Cancer Centers in Germany. Haematologica. 2020;105:2872–8.
Cook G, John Ashcroft A, Pratt G, Popat R, Ramasamy K, Kaiser M, et al. Real-world assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID-19 disease) in patients with multiple myeloma receiving systemic anti-cancer therapy. Br J Haematol. 2020;190:e83–6.
Chari A, Samur MK, Martinez-Lopez J, Cook G, Biran N, Yong K, et al. Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood. 2020;136:3033–40.
Varnai C, Palles C, Arnold R, Curley HM, Purshouse K, Cheng VWT, et al. Mortality among adults with cancer undergoing chemotherapy or immunotherapy and infected with COVID-19. JAMA Netw Open. 2022;5:e220130.
Shoumariyeh K, Biavasco F, Ihorst G, Rieg S, Nieters A, Kern WV, et al. Covid-19 in patients with hematological and solid cancers at a Comprehensive Cancer Center in Germany. Cancer Med. 2020;9:8412–22.
Zou J, Kurhade C, Patel S, Kitchin N, Tompkins K, Cutler M, et al. Neutralization of BA.4-BA.5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent Vaccine. N Engl J Med. N Engl J Med. 2023;388:854–7.
Musto P, Salmanton-García J, Sgherza N, et al. Multiple myeloma and SARS-CoV-2 infection: an European Hematology Association survey (EPICOVIDHA) of 1,221 patients through the different phase of COVID-19 pandemic. Fourth European Myeloma Network Meeting, Amsterdam, April 20-22 2023, abs. n. 067.
Blennow O, Salmanton-Garcia J, Nowak P, Itri F, Van Doesum J, Lopez-Garcia A, et al. Outcome of infection with omicron SARS-CoV-2 variant in patients with hematological malignancies: an EPICOVIDEHA survey report. Am J Hematol. 2022;97:E312–7.
Tregoning JS, Flight KE, Higham SL, Wang Z, Pierce BF. Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape. Nat Rev Immunol. 2021;21:626–36.
McDonald I, Murray SM, Reynolds CJ, Altmann DM, Boyton RJ. Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2. NPJ Vaccines. 2021;6:74.
Chavda VP, Soni S, Vora LK, Soni S, Khadela A, Ajabiya J. mRNA-based vaccines and therapeutics for COVID-19 and future pandemics. Vaccines (Basel). 2022;10:2150.
Gavriatopoulou M, Ntanasis-Stathopoulos I, Korompoki E, Terpos E, Dimopoulos MA. SARS-CoV-2 vaccines in patients with multiple myeloma. Hemasphere. 2021;5:e547.
Pratama NR, Wafa IA, Budi DS, Sutanto H, Asmarawati TP, Barlian Effendi G, et al. Effectiveness of COVID-19 vaccines against SARS-CoV-2 Omicron variant (B.1.1.529): a systematic review with meta-analysis and meta-regression. Vaccines (Basel). 2022;10:2180.
Wang L, Berger NA, Xu R. Risks of SARS-CoV-2 breakthrough infection and hospitalization in fully vaccinated patients with multiple myeloma. JAMA Netw Open. 2021;4:e2137575.
Rooney A, Bivona C, Liu B, Streeter D, Gong H, Khan Q. Risk of SARS-CoV-2 breakthrough infection in vaccinated cancer patients: a retrospective cohort study. J Hematol Oncol. 2022;15:67.
Sgherza N, Curci P, Rizzi R, Attolico I, Loconsole D, Mestice A, et al. SARS-CoV-2 infection in fully vaccinated patients with multiple myeloma. Blood Cancer J. 2021;11:201.
Wang L, Kaelber DC, Xu R, Berger NA. COVID-19 breakthrough infections, hospitalizations and mortality in fully vaccinated patients with hematologic malignancies: a clarion call for maintaining mitigation and ramping-up research. Blood Rev. 2022;54:100931.
Lee LYW, Tilby M, Starkey T, Ionescu MC, Burnett A, Hattersley R, et al. Association of SARS-CoV-2 spike protein antibody vaccine response with infection severity in patients with cancer: a national COVID cancer cross-sectional evaluation. JAMA Oncol. 2023;9:188–96.
Ludwig H, San-Miguel J, Munshi N, Sonneveld P, Mateos MV, Moreau P, et al. Covid-19 vaccination in patients with multiple myeloma: focus on immune response. Am J Hematol. 2021;96:896–900.
Terpos E, Rajkumar SV, Leung N. Neutralizing antibody testing in patients with multiple myeloma following COVID-19 vaccination. JAMA Oncol. 2022;8:201–2.
Nooka AK, Shanmugasundaram U, Cheedarla N, Verkerke H, Edara VV, Valanparambil R, et al. Determinants of neutralizing antibody response after SARS CoV-2 vaccination in patients with myeloma. J Clin Oncol. 2022;40:3057–64.
Cromer D, Steain M, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe. 2022;3:e52–61.
Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27:1205–11.
Van Oekelen O, Gleason CR, Agte S, Srivastava K, Beach KF, Aleman A, et al. Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma. Cancer Cell. 2021;39:1028–30.
Avivi I, Balaban R, Shragai T, Sheffer G, Morales M, Aharon A, et al. Humoral response rate and predictors of response to BNT162b2 mRNA COVID19 vaccine in patients with multiple myeloma. Br J Haematol. 2021;195:186–93.
Marchesi F, Pimpinelli F, Sperandio E, Papa E, Falcucci P, Pontone M, et al. The 12-week kinetics of anti-SARS-CoV-2 antibodies in different haematological cancers after vaccination with BNT162b2. Br J Haematol. 2022;196:362–7.
Pimpinelli F, Marchesi F, Piaggio G, Giannarelli D, Papa E, Falcucci P, et al. Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution. J Hematol Oncol. 2021;14:81.
Bird S, Panopoulou A, Shea RL, Tsui M, Saso R, Sud A, et al. Response to first vaccination against SARS-CoV-2 in patients with multiple myeloma. Lancet Haematol. 2021;8:e389–92.
Terpos E, Trougakos IP, Gavriatopoulou M, Papassotiriou I, Sklirou AD, Ntanasis-Stathopoulos I, et al. Low neutralizing antibody responses against SARS-CoV-2 in older patients with myeloma after the first BNT162b2 vaccine dose. Blood. 2021;137:3674–6.
Terpos E, Gavriatopoulou M, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, Malandrakis P, et al. The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment. Blood Cancer J. 2021;11:138.
Stampfer SD, Goldwater MS, Jew S, Bujarski S, Regidor B, Daniely D, et al. Response to mRNA vaccination for COVID-19 among patients with multiple myeloma. Leukemia. 2021;35:3534–41.
Ramasamy K, Sadler R, Jeans S, Varghese S, Turner A, Larham J, et al. COVID symptoms, testing, shielding impact on patient-reported outcomes and early vaccine responses in individuals with multiple myeloma. Br J Haematol. 2022;196:95–8.
Ghandili S, Schonlein M, Lutgehetmann M, Schulze Zur Wiesch J, Becher H, Bokemeyer C, et al. Post-vaccination anti-SARS-CoV-2-antibody response in patients with multiple myeloma correlates with low CD19+B-lymphocyte count and anti-CD38 treatment. Cancers (Basel). 2021;13:3800.
Lockmer S, Uttervall K, Kashif M, Svard C, Malmsten K, Fletcher-Torres E, et al. Antibody response to COVID-19 mRNA vaccine (Comirnaty) in myeloma patients treated with high-dose melphalan and/or immunotherapy. Am J Hematol. 2021;96:E443–6.
Schiller Salton N, Szwarcwort M, Tzoran I, Horowitz NA, Zuckerman T, Horesh N, et al. Attenuated humoral immune response following anti-SARS-CoV-2 vaccine in heavily pretreated patients with multiple myeloma and AL amyloidosis. Am J Hematol. 2021;96:E475–8.
Chan WY, Howells L, Wilson W, Sanchez E, Ainley L, Chavda SJ, et al. Serological response to the BNT162b2 mRNA or ChAdOx1 nCoV-19 COVID-19 vaccine after first and second doses in patients with plasma cell disorders: influence of host and disease factors. Br J Haematol. 2022;196:e21–6.
Salvini M, Maggi F, Damonte C, Mortara L, Bruno A, Mora B, et al. Immunogenicity of anti-SARS-CoV-2 Comirnaty vaccine in patients with lymphomas and myeloma who underwent autologous stem cell transplantation. Bone Marrow Transpl. 2022;57:137–9.
Bitoun S, Henry J, Vauloup-Fellous C, Dib N, Belkhir R, Mouna L, et al. Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls. J Hematol Oncol. 2021;14:166.
Chung DJ, Shah GL, Devlin SM, Ramanathan LV, Doddi S, Pessin MS, et al. Disease- and therapy-specific impact on humoral immune responses to COVID-19 vaccination in hematologic malignancies. Blood Cancer Disco. 2021;2:568–76.
Rahav G, Lustig Y, Lavee J, Ohad B, Magen H, Hod T, et al. BNT162b2 mRNA COVID-19 vaccination in immunocompromised patients: a prospective cohort study. EClinicalMedicine. 2021;41:101158.
Shah MR, Gabel A, Beers S, Salaru G, Lin Y, Cooper DL. COVID-19 vaccine responses in patients with plasma cell dyscrasias after complete vaccination. Clin Lymphoma Myeloma Leuk. 2022;22:e321–6.
Ghandili S, Schonlein M, Wiessner C, Becher H, Lutgehetmann M, Brehm TT, et al. Lymphocytopenia and anti-CD38 directed treatment impact the serological SARS-CoV-2 response after prime boost vaccination in patients with multiple myeloma. J Clin Med. 2021;10:5499.
Henriquez S, Zerbit J, Bruel T, Ouedrani A, Planas D, Deschamps P, et al. Anti-CD38 therapy impairs SARS-CoV-2 vaccine response against alpha and delta variants in patients with multiple myeloma. Blood. 2022;139:942–6.
Konishi Y, Sklavenitis-Pistofidis R, Yue H, Ferrari F, Redd RA, Lightbody ED, et al. Attenuated response to SARS-CoV-2 vaccine in patients with asymptomatic precursor stages of multiple myeloma and Waldenstrom macroglobulinemia. Cancer Cell. 2022;40:6–8.
Greenberg RS, Ruddy JA, Boyarsky BJ, Werbel WA, Garonzik-Wang JM, Segev DL, et al. Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with multiple myeloma. BMC Cancer. 2021;21:1354.
Haggenburg S, Lissenberg-Witte BI, van Binnendijk RS, den Hartog G, Bhoekhan MS, Haverkate NJE, et al. Quantitative analysis of mRNA-1273 COVID-19 vaccination response in immunocompromised adult hematology patients. Blood Adv. 2022;6:1537–46.
Terao T, Yamashita T, Fukumoto A, Kamura Y, Ikeda D, Kuzume A, et al. Low clinical protective response to SARS-CoV-2 mRNA COVID-19 vaccine in patients with multiple myeloma. Int J Hematol. 2022;115:737–47.
Hoornaert E, Dachy F, Hansenne A, Bailly S, van Maanen A, Gruson D, et al. COVID-19: impact of vaccination in myeloma patients. Ann Hematol. 2022;101:1607–8.
Abdallah AO, Mahmoudjafari Z, Atieh T, Ahmed N, Cui W, Shune L, et al. Neutralizing antibody responses against SARS-CoV-2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination. Eur J Haematol. 2022;109:458–64.
Zaleska J, Kwasnik P, Paziewska M, Purkot J, Szabelak A, Jurek M, et al. Response to anti-SARS-CoV-2 mRNA vaccines in multiple myeloma and chronic lymphocytic leukemia patients. Int J Cancer. 2023;152:705–12.
Gung C, McGuire R, George M, Abdulkareem A, Belden KA, Porcu P, et al. Antibody response to SARS-CoV-2 vaccination in patients with lymphoproliferative disorders and plasma cell dyscrasias: anti-lymphoma therapy as a predictive biomarker of response to vaccination. Front Oncol. 2022;12:840451.
Ramasamy K, Sadler R, Jeans S, Weeden P, Varghese S, Turner A, et al. Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response. Br J Haematol. 2022;197:293–301.
Pettine L, Bortolotti M, Fattizzo B, Da Via MC, Consonni D, Pompa A, et al. Response to SARS-CoV-2 vaccination and antibodies persistence in multiple myeloma patients. Hematol Oncol. 2023;41:210–12.
Dhakal B, Abedin S, Fenske T, Chhabra S, Ledeboer N, Hari P, et al. Response to SARS-CoV-2 vaccination in patients after hematopoietic cell transplantation and CAR T-cell therapy. Blood. 2021;138:1278–81.
Ehmsen S, Asmussen A, Jeppesen SS, Nilsson AC, Osterlev S, Vestergaard H, et al. Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer. Cancer Cell. 2021;39:1034–6.
Herzog Tzarfati K, Gutwein O, Apel A, Rahimi-Levene N, Sadovnik M, Harel L, et al. BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies. Am J Hematol. 2021;96:1195–203.
Agha ME, Blake M, Chilleo C, Wells A, Haidar G. Suboptimal response to coronavirus disease 2019 messenger RNA vaccines in patients with hematologic malignancies: a need for vigilance in the postmasking era. Open Forum Infect Dis. 2021;8:ofab353.
Benda M, Mutschlechner B, Ulmer H, Grabher C, Severgnini L, Volgger A, et al. Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients. Br J Haematol. 2021;195:523–31.
Re D, Barriere J, Chamorey E, Delforge M, Gastaud L, Petit E, et al. Low rate of seroconversion after mRNA anti-SARS-CoV-2 vaccination in patients with hematological malignancies. Leuk Lymphoma. 2021;62:3308–10.
Chiarucci M, Paolasini S, Isidori A, Guiducci B, Loscocco F, Capalbo M, et al. Immunological response against SARS-COV-2 after BNT162b2 vaccine administration is impaired in allogeneic but not in autologous stem cell transplant recipients. Front Oncol. 2021;11:737300.
Maneikis K, Sablauskas K, Ringeleviciute U, Vaitekenaite V, Cekauskiene R, Kryzauskaite L, et al. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study. Lancet Haematol. 2021;8:e583–92.
Shapiro LC, Thakkar A, Gali R, Gonzalez-Lugo JD, Bazarbachi AH, Rahman S, et al. High seroconversion rates amongst black and Hispanics with hematologic malignancies after SARS-CoV-2 vaccination. Leuk Lymphoma. 2022;63:2484–8.
Marasco V, Carniti C, Guidetti A, Farina L, Magni M, Miceli R, et al. T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies. Br J Haematol. 2022;196:548–58.
Ito Y, Honda A, Kurokawa M. COVID-19 mRNA vaccine in patients with lymphoid malignancy or anti-CD20 antibody therapy: a systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2022;22:e691–707.
Mohan M, Nagavally S, Shah NN, Michaelis L, Chhabra S, Souza AD, et al. Shorter interval between treatment and COVID immunization is associated with poor seroconversion in patients with hematological malignancies. Clin Lymphoma Myeloma Leuk. 2022;22:e495–7.
Aleman A, Van Oekelen O, Upadhyaya B, Beach K, Kogan Zajdman A, Alshammary H, et al. Augmentation of humoral and cellular immune responses after third-dose SARS-CoV-2 vaccination and viral neutralization in myeloma patients. Cancer Cell. 2022;40:441–3.
Susol O, Hajkova B, Zelena H, Hajek R. Third dose of COVID-19 vaccine restores immune response in patients with haematological malignancies after loss of protective antibody titres. Br J Haematol. 2022;197:302–5.
Wagner A, Garner-Spitzer E, Schotta AM, Orola M, Wessely A, Zwazl I, et al. SARS-CoV-2-mRNA booster vaccination reverses non-responsiveness and early antibody waning in immunocompromised patients - a phase four study comparing immune responses in patients with solid cancers, multiple myeloma and inflammatory bowel disease. Front Immunol. 2022;13:889138.
Thompson MA, Hallmeyer S, Fitzpatrick VE, Liao Y, Mullane MP, Medlin SC, et al. Real-world third COVID-19 vaccine dosing and antibody response in patients with hematologic malignancies. J Patient Cent Res Rev. 2022;9:149–57.
Frankel AE, Capozzola T, Andrabi R, Ahn C, Zhou P, He WT, et al. The effects of an mRNA Covid-19 vaccine booster on immune responses in cancer-bearing veterans. Med Res Arch. 2022;10:10.18103/mra.v10i7.2932. https://doi.org/10.18103/mra.v10i7.2932.
Enssle JC, Campe J, Buchel S, Moter A, See F, Griessbaum K, et al. Enhanced but variant-dependent serological and cellular immune responses to third-dose BNT162b2 vaccination in patients with multiple myeloma. Cancer Cell. 2022;40:587–9.
Azeem MI, Nooka AK, Shanmugasundaram U, Cheedarla N, Potdar S, Manalo RJ, et al. Impaired SARS-CoV-2 variant neutralization and CD8+T cell responses following 3 doses of mRNA vaccines in myeloma: correlation with breakthrough infections. Blood Cancer Discov. 2022.
Storti P, Marchica V, Vescovini R, Franceschi V, Russo L, Notarfranchi L, et al. Immune response to SARS-CoV-2 mRNA vaccination and booster dose in patients with multiple myeloma and monoclonal gammopathies: impact of Omicron variant on the humoral response. Oncoimmunology. 2022;11:2120275.
Rosati M, Terpos E, Bear J, Burns R, Devasundaram S, Ntanasis-Stathopoulos I, et al. Low spike antibody levels and impaired BA.4/5 neutralization in patients with multiple myeloma or Waldenstrom’s macroglobulinemia after BNT162b2 booster vaccination. Cancers (Basel). 2022;14:5816.
Faustini SE, Hall A, Brown S, Roberts S, Hill H, Stamataki Z, et al. Immune responses to COVID-19 booster vaccinations in intensively anti-CD38 antibody treated patients with ultra-high-risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial. Br J Haematol. 2023. https://doi.org/10.1111/bjh.18714. Online ahead of print.
Enssle JC, Campe J, Schwenger A, Wiercinska E, Hellstern H, Durrwald R, et al. Severe impairment of T-cell responses to BNT162b2 immunization in patients with multiple myeloma. Blood. 2022;139:137–42.
Aleman A, Upadhyaya B, Tuballes K, Kappes K, Gleason CR, Beach K, et al. Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma. Cancer Cell. 2021;39:1442–4.
Terao T, Naduka T, Ikeda D, Fukumoto A, Kamura Y, Kuzume A, et al. Depletion of CD38-positive regulatory T cells by anti-CD38 monoclonal antibodies induces a durable response to SARS-CoV-2 vaccination in patients with plasma cell dyscrasia. Br J Haematol. 2022;197:417–21.
Keppler-Hafkemeyer A, Greil C, Wratil PR, Shoumariyeh K, Stern M, Hafkemeyer A, et al. Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma. Nat Cancer. 2022.
Chung A, Banbury B, Vignali M, Huang CY, Asoori S, Johnson R, et al. Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias. Br J Haematol. 2022;199:520–8.
Malato J, Ribeiro RM, Fernandes E, Leite PP, Casaca P, Antunes C, et al. Stability of hybrid versus vaccine immunity against BA.5 infection over 8 months. Lancet Infect Dis. 2023;23:148–150.
Rosati M, Terpos E, Agarwal M, Karalis V, Bear J, Burns R, et al. Distinct neutralization profile of spike variants by antibodies induced upon SARS-CoV-2 infection or vaccination. Am J Hematol. 2022;97:E3–7.
Passamonti F, Romano A, Salvini M, Merli F, Porta MGD, Bruna R, et al. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies. Br J Haematol. 2021;195:371–7.
Chan WY, Sanchez E, Chavda SJ, Lecat CSY, Ainley L, Xu K, et al. Development of antibody response to SARS-CoV-2 following asymptomatic infection in patients with plasma cell disorders on immunomodulatory therapy. Br J Haematol. 2021;194:857–61.
Gavriatopoulou M, Terpos E, Malandrakis P, Ntanasis-Stathopoulos I, Briasoulis A, Gumeni S, et al. Myeloma patients with COVID-19 have superior antibody responses compared to patients fully vaccinated with the BNT162b2 vaccine. Br J Haematol. 2022;196:356–9.
Abella E, Trigueros M, Pradenas E, Munoz-Lopez F, Garcia-Pallarols F, Ben Azaiz Ben Lahsen R, et al. Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: a cross sectional study. Life Sci Alliance. 2022;5:e202201479.
Branagan AR, Duffy E, Gan G, Li F, Foster C, Verma R, et al. Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias. Blood Adv. 2021;5:1535–9.
Nguyen Y, Flahault A, Chavarot N, Melenotte C, Cheminant M, Deschamps P, et al. Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients. Clin Microbiol Infect. 2022;28:1654.e1651–4.
Food and Drug Administration. FDA releases important information about risk of COVID-19 due to certain variants not neutralized by Evusheld. 2023. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-releases-important-information-about-risk-covid-19-due-certain-variants-not-neutralized-evusheld. Accessed January 15, 2023.
Bruno G, Giotta M, Perelli S, De Vita G, Bartolomeo N, Buccoliero GB. Early access to oral antivirals in high-risk outpatients: good weapons to fight COVID-19. Viruses. 2022;14:2514.
Wong CKH, Au ICH, Lau KTK, Lau EHY, Cowling BJ, Leung GM. Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study. Lancet. 2022;400:1213–22.
Butler CC, Hobbs FDR, Gbinigie OA, Rahman NM, Hayward G, Richards DB, et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet. 2023;401:281–93.
Wong GL, Yip TC, Lai MS, Wong VW, Hui DS, Lui GC. Incidence of viral rebound after treatment with nirmatrelvir-ritonavir and molnupiravir. JAMA Netw Open. 2022;5:e2245086.
Takashita E, Yamayoshi S, Simon V, van Bakel H, Sordillo EM, Pekosz A, et al. Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants. N. Engl J Med. 2022;387:468–70.
Vangeel L, Chiu W, De Jonghe S, Maes P, Slechten B, Raymenants J, et al. Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antivir Res. 2022;198:105252.
Spiliopoulou V, Ntanasis-Stathopoulos I, Malandrakis P, Gavriatopoulou M, Theodorakakou F, Fotiou D, et al. Oral antivirals ritonavir-nirmatrelvir and molnupiravir are highly effective in patients with multiple myeloma and COVID-19; a single-center, prospective study. 19th International Myeloma Society Annual Meeting 2022, Los Angeles, California. Abstract P-161.
Bruno G, Perelli S, Palazzo G, De Vita G, Buccoliero GB. Oral antivirals against Sars-CoV-2 in multiple myeloma outpatients: a case series. Recent Prog Med. 2023;114:815–7.
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19 - final report. N. Engl J Med. 2020;383:1813–26.
Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N. Engl J Med. 2022;386:305–15.
Li M, Beck EJ, Laeyendecker O, Eby Y, Tobian AAR, Caturegli P, et al. Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern. Blood Adv. 2022;6:3678–83.
Hueso T, Godron AS, Lanoy E, Pacanowski J, Levi LI, Gras E, et al. Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancy and COVID-19: a longitudinal cohort and propensity score analysis. Leukemia. 2022;36:1025–34.
Filippatos C, Ntanasis-Stathopoulos I, Sekeri K, Ntanasis-Stathopoulos A, Gavriatopoulou M, Psaltopoulou T, et al. Convalescent plasma therapy for COVID-19: a systematic review and meta-analysis on randomized controlled trials. Viruses. 2023;15:765.
Gavriatopoulou M, Ntanasis-Stathopoulos I, Korompoki E, Fotiou D, Migkou M, Tzanninis IG, et al. Emerging treatment strategies for COVID-19 infection. Clin Exp Med. 2021;21:167–79.
Asteris PG, Kokoris S, Gavriilaki E, Tsoukalas MZ, Houpas P, Paneta M, et al. Early prediction of COVID-19 outcome using artificial intelligence techniques and only five laboratory indices. Clin Immunol. 2023;246:109218.
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ET, PM, ME, IN-S and HL reviewed the literature; ET, PM and HL drafted the first draft of the manuscript. All authors revised and approved the final version of the manuscript.
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Evangelos Terpos declares honoraria for advisory boards or lectures from Amgen, Astra/Zeneca, Bristol Myers Squibb, Eusa Pharma, GSK, Integris Pharma, Janssen, Pfizer, Sanofi and Takeda; research support (to institution) from Amgen, GSK, Janssen, Sanofi and Takeda; travel grants from Amgen, Eusa Pharma and Takeda. Pellegrino Musto declares honoraria for advisory boards or lectures from Celgene, Janssen-Cilag, Takeda, Amgen, BMS, Sanofi, Abbvie, Pfizer, Seattle Genetics and research support from Amgen, Sanofi. FG has received honoraria from Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, and GlaxoSmithKline; has served on the advisory boards for Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, GlaxoSmithKline, Roche, Adaptive Biotechnologies, Oncopeptides, bluebird bio, and Pfizer. NWCJD has received research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, Cellectis and BMS, and serves in advisory boards for Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, and Adaptive, all paid to institution. FS has received Grants from Celgene, Janssen, Oncopeptides, Sanofi, GSK, Targovax, Honoraria from Amgen, BMS, Takeda, Abbvie, Janssen, Novartis, SkyliteDX, Oncopeptides, Sanofi, Pfizer, Daiki-Sankyo, GSK, and Honoraria from participation in advisory boards for Abbvie, GSK, Celgene, Takeda, Janssen, Oncopeptides, Sanofi, BMS. CC declares Advisory board e/o speaker for Abbvie, AMGEN, Astellas, Beigene, BMS, Glycomimetics, GSK, Immunogen, Janssen, Jazz, Karyopharm, Menarini, Oncopeptides, Pfizer, Sanofi, Servier, Stemline, Takeda. Roman Hajek has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. PM declares honoraria and advisory boards from janssen, celgene, takeda, amgen, abbvie, Sanofi. Hermann Einsele declares Consulting or Advisory Role for BMS/Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, Novartis, Research Funding from BMS/Celgene, Janssen, Amgen, GSK, Sanofi, Honoraria from BMS/Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, Novartis, and Travel Support from BMS/Celgene, Janssen, Amgen, Takeda, Novartis, Sanofi. JS-M declares advisory boards and consulting services, on behalf of my Institution, for Abbvie, Amgen, BMS, Celgene, GSK, Haemalogix, Janssen-Cilag, Karyopharm, MSD, Novartis, Pfizer, Takeda, Regeneron, Roche, Sanofi, and SecuraBio. MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and AbbVie; has served on the advisory boards for Janssen and GlaxoSmithKline; has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Mundipharma. MAD declares honoraria from participation in Advisory Boards from Amgen, Takeda, BMS, Janssen, Beigene, Sanofi. PS declares research support from Amgen, BMS, Janssen, Sanofi, participation in Advisory Boards for Amgen, BMS, Janssen, Sanofi, Pfizer, Seagen, Karyopharm, Oncopeptides. HL declares research support from Amgen, Sanofi and honoraria for advisory boards/lectures from Celgene-BMS, Janssen-Cilag, Takeda, Amgen, Sanofi, Seattle Genetics, AbbVie, Pfizer, Oncopeptides. All other authors declare no conflicts of interest related to this paper.
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Terpos, E., Musto, P., Engelhardt, M. et al. Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN). Leukemia 37, 1175–1185 (2023). https://doi.org/10.1038/s41375-023-01920-1
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DOI: https://doi.org/10.1038/s41375-023-01920-1
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