CMV Reactivation in RRMM Patients Receiving Bispecific Antibody Therapy
Overview
In a real-world cohort of 85 CMV seropositive patients with relapsed/refractory multiple myeloma treated with bispecific antibodies, CMV reactivation occurred in 36% by 180 days. Steroid use for cytokine release syndrome was associated with increased risk of CMV detection, and clinically significant CMV infection was observed in a subset requiring antiviral therapy.
Background
Bispecific antibodies targeting BCMA or GPRC5D have shown efficacy in relapsed/refractory multiple myeloma but are associated with infectious complications, including viral infections. CMV reactivation during BsAb therapy has been reported but its incidence and risk factors remain unclear. This study implemented a CMV surveillance program to assess the incidence, risk factors, and clinical outcomes of CMV reactivation in RRMM patients receiving standard of care BsAbs at a single center.
Cumulative incidence of CMV reactivation at Day 90
28% (95% CI, 18–38%)
Cumulative incidence of CMV reactivation at Day 180
36% (95% CI, 25–47%)
Patients with CMV reactivation
26
Patients with CMV DNAemia >1000 IU/ml
6
Patients treated with CMV-directed therapy
4 (clinically significant CMV infection)
Median time to preemptive therapy
85.5 days (range 34–139 days)
Hazard ratio for CMV detection with steroid use
3.11 (95% CI, 1.25–7.74, p=0.01)
Key Findings
CMV reactivation occurred in 36% of CMV seropositive RRMM patients by 180 days of BsAb therapy.
Steroid treatment for cytokine release syndrome significantly increased the risk of CMV detection (HR 3.11).
Clinically significant CMV infection developed in 4 patients, all treated with BCMA-directed BsAbs, requiring antiviral therapy.
Baseline hematologic parameters and hypogammaglobulinemia were not associated with increased CMV reactivation risk.
IVIG prophylaxis did not reduce the risk of CMV detection or reactivation.
CMV reactivation was manageable with preemptive antiviral therapy and rarely necessitated interruption of BsAb treatment.
Clinical Implications
Routine CMV surveillance in CMV seropositive RRMM patients receiving BsAbs is important, especially in those receiving steroids for CRS. Early detection and preemptive antiviral therapy can effectively manage CMV reactivation and prevent severe disease. Clinicians should weigh the risks of steroid use and consider close monitoring to mitigate CMV-related complications during BsAb therapy.
Conclusion
CMV reactivation is a common and clinically relevant complication in RRMM patients undergoing BsAb therapy, particularly with steroid exposure. Proactive monitoring and timely antiviral intervention enable safe continuation of BsAb treatment.
References
Memorial Sloan Kettering Cancer Center 2022-2024 -- Reactivation of Cytomegalovirus in Patients Undergoing Bispecific Antibody Therapy for Relapsed/Refractory Multiple Myeloma
by Eric Jurgens, Tala Shekarkhand, Colin Rueda, David Nemirovsky, Andriy Derkach, Ross S. Firestone, Kevin Miller, Bruno Almeida Costa, Sridevi Rajeeve, Alexander M. Lesokhin, Neha Korde, Carlyn R. Tan, Hamza Hashmi, Hani Hassoun, Kylee Maclachlan, Urvi A. Shah, Malin Hultcrantz, Issam Hamadeh, Sergio A. Giralt, Gunjan L. Shah, Heather J. Landau, Michael Scordo, Saad Z. Usmani, Sham Mailankody, Zainab Shahid
