Cytomegalovirus reactivation with severe lymphopenia during elranatamab treatment: a case series in patients with triple-class refractory multiple myeloma

Abstract

Elranatamab (ELRA), a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, is effective in patients with triple-class refractory multiple myeloma (TCRMM). However, its T cell–engaging mechanism can induce profound immunosuppression. We retrospectively evaluated infectious complications, including cytomegalovirus (CMV) reactivation, in five TCRMM patients treated with ELRA at our institution. The median age was 77 years, and all patients experienced grade ≥3 lymphopenia. Four (80 %) developed CMV reactivation within 50 days of treatment initiation—markedly higher than the 1.8–5.7 % reported in clinical trials. All reactivation cases were detected by PCR (>500 IU/mL) and managed pre-emptively with valganciclovir; no CMV disease occurred. Absolute lymphocyte counts declined rapidly by day 8 (mean 287/μL) and remained suppressed for over two months in most patients. CD4⁺ T-cell counts were persistently low (22–75/μL) in four of five patients. Neutropenia was transient and inconsistent; bacterial infections occurred in two patients, and no fungal infections were observed. These real-world data suggest that treatment with ELRA in older, transplant-ineligible patients may be associated with a high risk of CMV reactivation than previously appreciated, likely driven by prolonged lymphopenia with a potential contribution from hypogammaglobulinemia. Our results underscore the importance of routine CMV monitoring and lymphocyte profiling during ELRA therapy. Further prospective studies are warranted to optimize infection surveillance and prophylactic strategies in this population. To our knowledge, this is the first case series from Japan to describe infectious complications of ELRA in routine practice, providing important real-world evidence for clinicians.