Vaccination against SARS-CoV-2: Suboptimal Response in Myeloma Patients Under Therapy

Evangelos Terpos, MD, PhD; Professor of Hematology
National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies, including CLL and MM. In a very recent study published in the August 2021 issue of Blood Cancer Journal, neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with mRNA vaccines on days 1 (before the first vaccine shot), and on days 22 and 50 post-the first vaccine dose [https://pubmed.ncbi.nlm.nih.gov/34341335/]. Patients with MM (n=213), SMM (n=38) and MGUS (n=25) and 226 healthy controls were enrolled in the study (NCT04743388).

Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine led to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 (P<0.001 for all comparisons). On day 50 (i.e., 4 weeks after the second vaccine dose of the Pfizer/BioNTech vaccine, Comirnaty), 114 (54%) MM patients had strong NAb titers (≥50%) compared to 183 (81%) of normal controls; while another 38 (18%) managed to develop moderate NAb titers (30-49%). Thus, approximately 28% of MM patients did not develop NAb antibodies in this study. Importantly, active treatment with either anti-CD38 monoclonal antibodies (Mabs) or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination.

On the contrary, MGUS patients had no differences from controls regarding the development of Nabs titers of ≥30% or ≥50% on D50.

Similar to the above results, van Oekelen and colleagues published in the August Issue of Cancer Cell the efficacy of vaccination with mRNA vaccines in 320 myeloma patients [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238657/]. Of the fully immunized MM patients, 84.2% (219/260) mounted measurable SARS-CoV-2 spike-binding IgG antibody levels which varied by three orders of magnitude (median 149 AU/mL, range: 5–7,882 AU/mL), and 41 individuals (15.8%) had values below the level of detection.

Patients receiving myeloma treatment had significantly lower SARS-CoV-2 spike-binding IgG antibody levels after two vaccine doses (p=0.004) compared to patients not receiving anti-myeloma therapy (median antibody level on active therapy: 70 AU/mL, compared to MM patients without active therapy: 183 AU/mL). Looking at treatment categories, the authors found significantly lower antibody levels for patients receiving anti-CD38-containing regimens (p < 0.001) and BCMA-targeted therapy (p = 0.003) but not for the other treatments (p = 0.55) compared to patients not actively receiving anti-myeloma therapy.

Based on the above results, it seems that approximately 15-30% of myeloma patients, and especially those under therapy with anti-CD38 or anti-BCMA containing regimens do not develop antibodies against SARS-CoV-2 after full vaccination. The best management for these patients is under thorough investigation. A third vaccine dose or the monthly use of monoclonal antibodies against SARS-CoV-2 are in clinical trials to show if they can offer any protection in MM patients who failed to develop antibodies after full vaccination. Till having the results of these studies, patients with suboptimal response to vaccination have to follow all protective measures and social distancing, especially during the pandemic of delta variant of the virus.