A pooled analysis published in Blood Advances found that half of patients with multiple myeloma (MM) who were treated with bispecific antibodies developed an infection, and a quarter developed grade III/IV infections. Moreover, a quarter of deaths were secondary to infection.
“Our study aimed to quantify and describe reported infectious adverse events (AEs) linked to the use of bispecific antibodies in MM treatment,” said corresponding author Samer Al Hadidi, MD, of the University of Arkansas for Medical Sciences in Little Rock. “We suggest that mitigating steps be taken to prevent infections or identify them early and treat them.”
The pooled analysis included all single-agent bispecific antibodies used in MM. Bispecific antibodies that target B-cell maturation antigen (BCMA), G protein-coupled receptor, family C, group 5, member D (GPRC5D), and Fc receptor-like 5 (FcRH5) were included. Studies that reported on the use of bispecific antibodies as part of combination therapy or allowed for prior use of other bispecific antibodies were excluded. The drugs included in the analysis were teclistamab, elranatamab, linvoseltamab, AMG 420, pavurutamab, alnuctamab, ABBV-383, talquetamab (weekly and biweekly dosing), intravenous (IV) talquetamab, and cevostamab.
The 11 trials published through December 2022 included 1,185 patients with relapsed or refractory MM and previous use of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Of the participants, 71.6% had been treated with an agent targeting BCMA. The pooled median follow-up was 6.1 months (range = 1.7-14.1).
Treatment-related AEs were reported in all of the studies. All grade AEs of interest included neutropenia in 38.6% (n=441/1,143), infections in 50% (n=542/1,083), and cytokine release syndrome in 59.6% (n=706/1,185) of patients. Grade 3-4 AEs included neutropenia in 34.8% (n=372/1,068), infections in 24.5% (n=272/1,110), pneumonia in 10% (n=52/506), and COVID-19 in 11.4% (n=45/395) of patients.
Compared with BCMA-targeted bispecific antibodies, non-BCMA-targeted bispecific antibodies (talquetmab [GPRC5D] and cevostumab [FcRH5]) were associated with lower rates of grade 3-4 neutropenia, at 39.2% and 25.3%, respectively (p=0.001), and lower rates of grade 3-4 infections, at 30.0% and 11.9%, respectively (p=0.01). Hypogammaglobulinemia was reported in four studies in 75.3% (n=256/340) of patients, with IV immunoglobulin used in 48% (n=123/256) of them. Death was reported in 110 patients, of which 25.5% (n=28) were secondary to infections.
There is “no consensus on preventive measures to avoid infections. Our findings will help in implementing strategies to prevent and identify infections,” said Dr. Al Hadidi. “Moreover, our findings highlighted the possible opportunistic infections, some of which were associated with severe infections, and thus suggest that prophylactic anti-microbials and other supportive measures, such as immunoglobulin infusions, may be helpful in preventing such infection complications.
“Our study also indicated that we need to improve the clinical trial reporting of infections, as well as have preventive measures as part of clinical trials to help in understanding which measures are helpful. This is important since those agents are being used more often in earlier settings in MM,” Dr. Al Hadidi added. “Future trials need to consider fixed-duration therapy or less frequent dosing to help reduce the risk of infections.”
Limitations of the study include the retrospective design, inconsistent reporting on infections, and the short duration of follow-up.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Mazahreh F, Mazahreh L, Schinke C, et al. Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis. [published online ahead of print, 2023 Jun 30] Blood Adv. 2023;7(13):3069-3074.
