Treatment With Rituximab Prior to COVID-19 Vaccination Lowers Antibody Response in Patients With Lymphoma

Administration of rituximab (Rituxan) for the treatment of B-cell non-Hodgkin lymphoma prior COVID-19 vaccination significantly lowered the number of patients who developed blocking antibodies for the virus compared with a healthy control group, according to a study published in Blood Cancer Discovery.¹

The study found that 55% of patients with lymphoma (n = 126) developed blocking antibodies following mRNA vaccination compared with 100% of patients in the control group (n = 20; P < .001). Further, a similar vaccine response was found in treatment-naïve patients and controls.

“This finding is likely to be practice-changing,” said senior study author Ronald Levy, MD, Robert K. and Helen K. Summy Professor at Stanford School of Medicine, in a press release.² “We found that antibody responses to the COVID-19 vaccine were blunted in people who received rituximab up to a year before vaccination. But if they were vaccinated prior to treatment, most responded and were able to hold on to that response during their rituximab treatment.”

To evaluate why patients with lymphoma showed poor responses to COVID-19 vaccination, the study authors analyzed blocking antibodies, total anti-spike immunoglobulin, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls at 1 and 4 months after COVID-19 vaccination between February 1, 2021, and June 30, 2021.

Samples were collected from 146 individuals 1 month after the last vaccine dose (median, 28 days) and from 128 individuals 4 months after the last vaccine dose (median, 127 days). Nearly all individuals were administered an mRNA-based COVID-19 vaccine.

Seventy percent of patients had follicular lymphoma or diffuse large B-cell lymphoma. Among the 126 patients with lymphoma, 17 had no prior treatment, 31 were administered a CD20-directed antibody within the prior 6 months, 65 had not received treatment at least 6 months prior to vaccination, 12 were receiving a BTK inhibitor, and 1 was administered lenalidomide (Revlimid) monotherapy.

Approximately half of patients administered a BTK inhibitor at the time of vaccination without prior or current CD20-directed treatment developed blocking antibodies (n = 5/12).

The study showed that the time since the last CD20-directed treatment was a significant independent predictor of vaccine response. None of the 9 patients administered a CD20-directed antibody within 1 month prior to vaccination developed responses to the vaccine.

Furthermore, none of the 31 patients administered a CD20 antibody within 6 months prior to vaccination developed blocking antibodies; however, 76% of patients who received prior treatment—but not recent treatment—did develop blocking antibodies.

Patients who began a CD20-directed treatment shortly after achieving a vaccine-induced antibody response were generally able to maintain the response during treatment.

To better understand the length of the impact from CD20-directed therapy on vaccine response, the researchers evaluated patients administered prior CD20-directed treatment (n = 100). The time since the last anti-CD20 dose ranged from 1 week to 17.5 years prior to vaccination.

The researchers found a significant association between the time interval and blocking antibody response. The likelihood of vaccine response remained low until at least 12 months following the last CD20-directed treatment. Similar results were found in a subset of 16 patients administered a CD20-targeted antibody alone without prior or current chemotherapy.

“When we compared the effects of chemotherapy or other drugs, we found that it was mainly recent rituximab treatment that limited a person’s response to the vaccines,” Levy said in the release.

Fifteen of 126 patients were completely vaccinated against COVID-19 before starting treatment with rituximab, 10 of whom developed a blocking antibody response to the virus. In 6 of these patients, the response lasted at least 4 months after starting rituximab.

“It’s so important to give people the chance to mount an effective immune response to vaccinations, particularly now,” Levy said in the release. “There has been controversy in the field about the value of continuing rituximab treatment after the initial therapy because doing so has not been shown to help these patients live longer. Our study suggests this practice of extended treatment should probably be abandoned in the COVID era.”

References

1. Shree T, Shankar V, Lohmeyer JJk, et al. CD20-targeted therapy ablates de novo antibody response to vaccination but spares pre-established immunity. Blood Cancer Discov. Published online ahead of print January 6, 2022. doi:10.1158/2643-3230.BCD-21-0222.
2. Prior treatment with cancer drug likely renders COVID-19 vaccine ineffective, study finds. News release. Stanford Medicine. February 2, 2022. Accessed February 3, 2022. https://stan.md/3HwbHIs