Infection risk in 158 patients with relapsed/refractory multiple myeloma treated with bispecific antibodies: a single-center experience

Four bispecific antibodies (BsAb) are approved for the treatment of relapsed refractory multiple myeloma (RRMM), but their use is associated with infection risks, requiring mitigation strategies. This single-center retrospective study evaluated the incidence, etiology, and risk factors for infections in 158 RRMM patients treated with BsAb. A total of 101 patients received BCMAxCD3 BsAb (teclistamab and elranatamab), and 57 GPRC5DxCD3 BsAb (talquetamab). Prophylactic measures included herpes zoster and Pneumocystis jirovecii coverage, along with monthly intravenous immunoglobulin (IVIG) as primary prophylaxis. Tocilizumab was used for the prevention of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and BsAb frequency was reduced in responding patients. Cytomegalovirus (CMV) viral load was assessed monthly. Median follow-up was 6.1 versus 4.5 months for anti-BCMA versus anti-GPRC5D group. The cumulative incidence of the first any-grade infection at 5 and 10 months was 38.6% and 47.9% in the anti-BCMA group, and 28.1% and 30.3% in the anti-GPRC5D group (P=0.06). IVIG administration significantly reduced the risk of grade ≥3 infections in multivariate analysis (hazard ratio =0.38; P<0.01). Most infections were viral (60%), mainly upper respiratory (38%). The cumulative incidence of CMV infections at 5 and 10 months was 45.1% and 48% in the anti-BCMA group, versus 27.3% at both time points in the anti-GPRC5D group (P=0.03). With the limitation of a short follow-up, our results showed a higher incidence of anygrade infections in patients receiving anti-BCMA BsAb. Primary IVIG prophylaxis reduced severe infections. CMV infections were more frequent in patients treated with anti-BCMA agents.