Although the 5-year survival rate for multiple myeloma has increased over the past 2 decades—from about 35% in 2000 to approximately 62% in 2015—due to more effective therapies, the cancer remains incurable. According to the American Cancer Society, this year, nearly 36,000 individuals will be diagnosed with multiple myeloma and about 13,000 will die from the disease.

The development of highly effective immunotherapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies, are demonstrating overall response rates of between 60% and 70% for heavily pretreated patients with multiple myeloma. Bispecific antibodies targeting the B-cell maturation antigen (BCMA) protein are increasingly being used in the treatment of the blood cancer, and while anti-BCMA bispecific antibodies have exhibited impressive efficacy against the disease, serious—sometimes fatal—infections have been reported in patients receiving these therapies, which may be the possible result of treatment-induced depletion of patients’ antibodies.

A retrospective study by Lancman et al published in Blood Cancer Discovery investigating supplementing patient antibody levels through intravenous immunoglobulin (IVIG) to mitigate the risk of infection has found that IVIG reduced the risk of grade 3 to 5 infections by 90% in patients with relapsed or refractory multiple myeloma treated with anti-BCMA bispecific antibodies.

Study Methodology

The researchers conducted a retrospective analysis of 37 heavily pretreated patients with multiple myeloma treated at Mount Sinai Hospital in New York City with a BMCA-targeting bispecific antibody as monotherapy on four clinical trials (ClinicalTrials.gov identifiers NCT03287908, NCT03761108, NCT04083534, and NCT03145181) between January 1, 2019 and June 30, 2022. Data were collected on baseline characteristics; treatment; disease response; hypogammaglobulinemia; infections; and infection prophylaxis, including IVIG.

Results

The study found that among 37 patients, 15 (41%) experienced a grade 3 to 5 infection, with two infection-related deaths occurring during deep remissions. Most infections (84%) occurred during disease remissions. The cumulative probability of grade 3 to 5 infection increased over time with no plateau. Among responders (n = 26), profound hypogammaglobulinemia occurred in 100% and continued throughout the entire duration of treatment. During periods when patients were receiving IVIG, the rate of grade 3 to 5 infections was 90% lower than during observation (incidence rate ratio = 0.10, 95% confidence level (CI) = 0.01–0.80, P = .0307). No other risk factors for infection were identified.

“This study demonstrates that profound hypogammaglobulinemia is universal with BCMA-targeted bispecific antibodies, with IVIG potentially abrogating most of the infection risk,” concluded the study researchers.

Clinical Significance

“This study demonstrates that IVIG is associated with a substantially reduced risk of serious infections in patients receiving anti-BCMA bispecific antibodies,” said lead study author Guido Lancman, MD, Clinical Associate at the Princess Margaret Cancer Centre of the University Health Network and Adjunct Assistant Professor at the University of Toronto. “Given the very high rates of serious infections and deaths in patients receiving these treatments, this study supports a proactive rather than a reactive approach—meaning initiation of IVIG prophylaxis from the beginning rather than waiting for patients to experience complications.” 

Disclosure: Funding for this study was provided by the Polish National Agency for Academic Exchange. For full disclosures of the study authors, visit aacrjournals.org/bloodcancerdiscov.