CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

Abstract

To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies postvaccination, compared with 100% of controls. When evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible. Significance: In a large cohort of patients with B-cell lymphoma, time since anti-CD20 treatment was an independent predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate an antibody response that endures through anti-CD20–containing treatment. This article is highlighted in the In This Issue feature, p. 85

Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

“…We observed lower IgG-binding titers against the Wuhan strain spike protein in patients with NHL/CLL compared with healthy controls, especially after recent anti-CD20-directed therapy. While this observation has been reported, [16][17][18][19]21,[26][27][28] we further improve on our understanding of antibody responses in patients with NHL/CLL by also showing decreased IgM and IgA titers, which may confer protection at mucosal surfaces. 37 Additionally, our lymphocyte profile analysis provides biologic context for the decreased response observed after recent anti-CD20-directed therapy.…”

Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses

“…However, our data suggest that vaccination prior to B cell-targeted therapy may be important to achieve long-term benefits. In support of this notion, two recent studies, with a relatively small number of patients, provide evidence that SARS-CoV2 vaccination prior to anti-CD20 mAb had superior induction of antibody responses compared to when the agents were administered in reverse order (46, 47). In summary, our findings highlight the discordance between de novo and pre-existing antibodies.…”

Current and emerging monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies in treatment of lymphoma

“…Levy et al. [19] evaluated the response to COVID-19 vaccine in 126 lymphoma patients who received rituximab by measuring antibodies to viral spike proteins. The last dose of rituximab varied from days to 18 years prior the vaccine.…”

“…Results showed that patients who received rituximab within 12 months prior to vaccine administration are less likely to develop antibodies. 10 of the 15 patients who received the vaccine prior to initiation of rituximab developed antibodies [19] . The optimal timing of receiving COVID-19 vaccination to mount a response after finishing rituximab therapy is unknown yet.…”