Neutralizing antibody responses against <scp>SARS‐CoV</scp>‐2 in patients with plasma cell disorders who are on active treatment after two doses of <scp>mRNA</scp> vaccination

Abdallah, Al‐Ola; Mahmoudjafari, Zahra; Atieh, Tahani; Ahmed, Nausheen; Cui, Wei; Shune, Leyla; Mohan, Meera; McGuirk, Joseph; Remker, Cassie; Foss, Margaret; Karloff, Ellie; Fitch, Heather; Atrash, Shebli

doi:10.1111/ejh.13826

Cited by 11 publications

(6 citation statements)

References 22 publications

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“…But on the other hand, there are, as yet, no clear guidelines for antimicrobial prophylaxis therapy in cases of RRMM. Although we did not observe a high incidence of coronavirus disease 2019 (COVID-19) infection in our patient population, daratumumab has been reported to have lower neutralizing antibodies after vaccination and thus higher risk of infection [ 24 ]. Immunoglobulin replacement therapy has not improved outcomes and is associated with increased risk of thrombosis and renal injury [ 25 ].…”

Section: Discussionmentioning

confidence: 70%

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone

Alkharabsheh¹,

Bellman²,

Mahmoudjafari³

et al. 2023

J Hematol

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Background Daratumumab, pomalidomide, and dexamethasone (DPd) is an effective option for treatment of patients with relapsed/refractory multiple myeloma (RRMM). In this study, we sought to analyze the risk of hematological and non-hematological toxicities in patients who responded to DPd treatment. Methods We analyzed 97 patients with RRMM who were treated with DPd between January 2015 and June 2022. The patients and disease characteristics, as well as safety and efficacy outcomes were summarized as descriptive analysis. Results The overall response rate for the entire group was 74% (n = 72). The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common grade III/IV non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%). The incidence of dose reduction/interruption was 76% (55/72), which was due to hematological toxicity in 73% of the cases. The most common reason for discontinuing treatment was disease progression in 61% (44 out of 72 patients). Conclusions Our study revealed that patients who respond to DPd are at high risk of dose reduction or treatment interruption because of hematological toxicity, typically due to neutropenia and leukopenia leading to increased risk of hospitalization and pneumonia.

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Section: Discussionmentioning

confidence: 70%

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone

Alkharabsheh¹,

Bellman²,

Mahmoudjafari³

et al. 2023

J Hematol

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“…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 – 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 ].…”

Section: Methodsmentioning

confidence: 99%

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

et al. 2023

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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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“…In patients with MM, SARS-CoV-2 infection has been associated with a severe clinical course and high mortality rates, due to the concomitant disease- and treatment-related immunosuppression [ 1 ]. Furthermore, MM patients respond poorly to vaccination despite adequate immunization, especially those on treatment with anti-CD38 or anti-BCMA therapies [ 2 , 3 , 4 , 5 ]. Thus, MM patients are at a higher risk for breakthrough infection compared with noncancer patients or patients with solid tumor, and supportive measures along with prophylactic use of monoclonal antibodies against SARS-CoV-2 are needed [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Use of Oral Antivirals Ritonavir-Nirmatrelvir and Molnupiravir in Patients with Multiple Myeloma Is Associated with Low Rates of Severe COVID-19: A Single-Center, Prospective Study

Spiliopoulou

Ntanasis‐Stathopoulos

Malandrakis

et al. 2023

Viruses

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In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with a severe clinical course and high mortality rates due to the concomitant disease- and treatment-related immunosuppression. Specific antiviral treatment involves viral replication control with monoclonal antibodies and antivirals, including molnupiravir and the ritonavir-boosted nirmatrelvir. This prospective study investigated the effect of these two agents on SARS-CoV-2 infection severity and mortality in patients with MM. Patients received either ritonavir-nirmatrelvir or molnupiravir. Baseline demographic and clinical characteristics, as well as levels of neutralizing antibodies (NAbs), were compared. 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 a 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) in the univariate analysis. In conclusion, ritonavir-nirmatrelvir and molnupiravirmay prevent severe disease in MM patients with SARS-CoV-2 infection. This prospective study indicated the comparable effects of the two treatment options, providing an insight for further research in preventing severe COVID-19 in patients with hematologic malignancies.

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Neutralizing antibody responses against SARS‐CoV‐2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination

Cited by 11 publications

References 22 publications

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

Use of Oral Antivirals Ritonavir-Nirmatrelvir and Molnupiravir in Patients with Multiple Myeloma Is Associated with Low Rates of Severe COVID-19: A Single-Center, Prospective Study

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