Risk of Infections in Multiple Myeloma Patients Treated with Bispecific Antibodies

Abstract

Introduction There are currently 3 FDA-approved bispecific antibodies (BsAbs) for treatment of relapse refractory multiple myeloma (RRMM) for patients (pts) that received 4 or more prior lines of therapy including proteasome inhibitors, immunomodulatory drugs and anti-CD38 monoclonal antibodies. While these BsAbs have shown unprecedented clinical activity, there is accumulating evidence that they are associated with significant risk of infections. Risk mitigation strategies are essential to allow for safer administration of these effective agents. In this context, we evaluated infectious complications of pts who received BCMA x CD3 (teclistamab and elranatamab) and GPRC5D x CD3 (talquetamab) BsAbs. Methods Of the 141 RRMM pts treated with BsAbs from 12/21/22 until 6/28/24, we have analyzed the infectious complications with adequate homogenous institutional (Emory University Winship Cancer Institute) consensus guidelines. Adverse events were graded according to the CTCAE, version 5.0. Baseline cytomegalovirus (CMV), Epstein-Barr virus (EBV) and monthly surveillance were obtained. Prophylactic antivirals were administered in all pts. All-infections specific variables were collected from day 0 until the date of next line of therapy or last follow-up, with a data cut-off of 6/30/24. Seventeen pts received two different BsAbs in two separate lines of therapy. Pts receiving two consecutive BsAbs during the study period were censored at the start date of the second BsAb, and data were collected independently for each single BsAb. The median follow-up for the entire cohort was 7.1 months (teclistamab vs elranatamab vs talquetamab were 10.2 vs 4.2 vs 4.2 months). Infections were reported based on Ludwig et al. Blood Adv 2024; bloodadvances.2024013461. Results A total of 158 BsAbs in different lines of therapy were performed in 141 pts. Administrations of BCMA vs GPRC5D target BsAbs were 101 (64%, teclistamab [n=77] and elranatamab [n=24]) vs 57 (36%, talquetamab). The median age of pts receiving teclistamab vs elranatamab vs talquetamab was 66 years (range 43-87) vs 63 (44-81) vs 66 (38-89). Similarly, median prior lines were 5 (2-13) vs 5 (2-14) vs 6 (3-16), respectively. Prior BCMA target therapies exposure for teclistamab vs elranatamab vs talquetamab with antibody-drug conjugate vs chimeric antigen receptor T-cell therapy (CAR-T) vs BsAbs were 10.4%, 12.5%, 15.8% vs 15.6%, 12.5%, 40.4% vs 3.9%, 4.2%, 45.6%, respectively. The receipt of monthly intravenous immunoglobulin (IVIG) for teclistamab vs elranatamab vs talquetamab was 74.3% vs 45.8% (p=0.011) vs 70.9%, respectively. The median time from treatment initiation to the first infection was 1.77 months (0-12.35). The median time to ≥ grade 3 neutropenia was 0.8 months. The rates of prophylactic tocilizumab administration were 94.8% vs 100% vs 100%. While there were no EBV reactivations, any grade CMV reactivations for BCMA vs GPRC5D BsAbs were 49.3% vs 20.8%, p<0.001. CMV reactivations for teclistamab vs elranatamab were 42.2% vs 62.5%, p=0.088, respectively. The rates of ≥ grade 2 CMV reactivations were 6.7% vs 8.3% vs 1.9% for teclistamab vs elranatamab vs talquetamab. Eighty-seven (55%) - 61% vs 100% vs 28% any grade infections were observed in 56 (35.4%) pts. Of these 41 (26%) - 9% vs 63% vs 16% ≥ grade 3 events occurred in 31 pts (23.4%). All grade and ≥ grade 3 infections per month per 100 pts occurred in 7.7 vs 99.2 vs 12, and 1.16 vs 62 vs 6.7 for teclistamab vs elranatamab vs talquetamab. IVIG significantly reduced the risk of ≥ grade 3 infections - 14.3% vs 31.3%, p=0.014. Conclusions On routine surveillance, CMV reactivations for BCMA vs GPRC5D BsAbs were 49.3% vs 20.8%, respectively, while ≥ grade 2 CMV reactivations were 7.2% vs 1.9%, likely from our practice of stopping BsAb at the sign of CMV reactivation. The overall ≥ grade 3 infections (as single occurrence) are significantly lower compared to the reported literature at 19.6% (BCMA vs GPRC5D BsAbs: 23.8% vs 12.3%, p = 0.06). Higher rates of infection from elranatamab from our institutional cohort are likely from less usage of IVIG, higher rates of prior BsAbs, smaller number of pts and shorter follow-up. Reporting infections per month per 100 pts will allow for accurate estimate of infections with BsAbs.