Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with multiple myeloma

Greenberg, Ross S.; Ruddy, Jake A; Boyarsky, Brian J.; Werbel, William A; Garonzik-Wang, Jacqueline M; Segev, Dorry L.; Imus, Philip

doi:10.1186/s12885-021-09097-5

Cited by 12 publications

(12 citation statements)

References 22 publications

(9 reference statements)

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“…Initial vaccination (2x Comirnaty) of the patient described by us while still receiving Pomalidomide treatment as maintenance therapy after remission of multiple myeloma failed to induce SARS-CoV-2 seroconversion ( Figure 1 and Figure 2 ). This was in contrast to other reports showing that ongoing Pomalidomide treatment did not affect the response [ 17 , 18 , 19 ]. Common risk factors for vaccination failure such as low B cell counts (<30/µL), current anti-CD38 monoclonal antibody treatment or active disease with more than one treatment line were also absent in our patient [ 17 , 20 ].…”

Section: Discussioncontrasting

confidence: 99%

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

et al. 2022

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Background: Prophylactic vaccination against infectious diseases may induce a state of long-term protection in the otherwise healthy host. However, the situation is less predictable in immunocompromised patients and may require adjustment of vaccination schedules and/or basic therapy. Methods: A patient in full remission of multiple myeloma since the last three years and on long-term maintenance therapy with pomalidomide, a drug inhibiting angiogenesis and myeloma cell growth, was vaccinated twice with Comirnaty followed by two vaccinations with Vaxzevria. Seroconversion and SARS-CoV-2-specific cellular responses were monitored. Results: No signs of seroconversion or T cellular memory were observed after the first “full immunization” with Comirnaty. Consequently, long-term-maintenance therapy with Pomalidomide was stopped and two additional shots of Vaxzevria were administered after which the patient seroconverted with Spike(S)-protein specific antibody levels reaching 49 BAU/mL, mild S-peptide pool-specific T cell proliferation, effector cytokine production (IL-2, IL-13), and T cellular activation with increased numbers of CD3+CD4+CD25+ T cells as compared to vaccinated and non-vaccinated control subjects. However, despite suspension of immunosuppression and administration of in total four consecutive heterologous SARS-CoV-2 vaccine shots, the patient did not develop neutralizing RBD-specific antibodies. Conclusions: Despite immunomonitoring-based adjustment of vaccination and/or therapy schedules vaccination success, with clear correlates of protection, the development of RBD-specific antibodies could not be achieved in the immunocompromised patient with current SARS-CoV-2 vaccines. Thus, our report emphasizes the need for improved active and passive immunization strategies for SARS-CoV-2 infections.

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Section: Discussioncontrasting

confidence: 99%

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

et al. 2022

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“…In this setting, there have been reports showing the response to vaccines in subjects with hematological cancer [23][24][25][26][27][28], such as Case 1 in this study. For example, Benda et al observed a total of 259 hemato-oncological patients vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart.…”

Section: Discussionmentioning

confidence: 74%

Different Clinical Outcomes of COVID-19 in Two Healthcare Workers Vaccinated with BNT162b2 Vaccine, Infected with the Same Viral Variant but with Different Predisposing Conditions for the Progression of the Disease

et al. 2022

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“…Vaccinated myeloma patients were at >350% less risk of severe outcomes and 331% less risk of death following COVID-19 infection compared to unvaccinated myeloma patients. An earlier study demonstrated that 2/3 rd of vaccinated myeloma patients show some response to mRNA vaccines, although vaccination may only provide partial protection from infection, while 1/3 rd failed to respond based on background IgG levels of 50IU/ml 15 . However, the threshold/cut-offs were primarily probabilistic, with no clinical follow-up correlating relevant anti-spike IgG levels with protection in vaccinated patients.…”

Section: Discussionmentioning

confidence: 99%

Sample average treatment effect on the treated analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

Mitra

Mukherjee

Mazumder

et al. 2022

Preprint

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Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the propensity score matching (PSM) method. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

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Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with multiple myeloma

Cited by 12 publications

References 22 publications

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

Different Clinical Outcomes of COVID-19 in Two Healthcare Workers Vaccinated with BNT162b2 Vaccine, Infected with the Same Viral Variant but with Different Predisposing Conditions for the Progression of the Disease

Sample average treatment effect on the treated analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

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