Physician Assistant Winship Cancer Institute, Emory University atlanta, Georgia, United States
Introduction: Multiple myeloma (MM) is associated with an increased risk of infections. The risk of infections is variable and related to tumor burden, underlying comorbidities, and treatments used. Three bispecific antibodies (BsAbs), teclistamab-cqyv (Tec), elranatamab-bcmm (Elra), and taqluetamab-tgvs (Talq), have been granted accelerated approval by both the FDA and EMA for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). In the clinical trials for approval, patients that were treated with BsAbs had significantly higher rates of infection. Infectious complications related to the use of BsAbs are not well described. Recommendations for infectious screening and prophylaxis can be variable; therefore, we implemented an institutional protocol to screen all BsAbs patients for infections and the use of prophylactic antimicrobials.
Methods: All patients receiving BsAbs at our institution received antiviral prophylaxis and pneumocystis jiroveci pneumonia (PJP) prophylaxis at the initiation of therapy. Monthly IVIG was started on cycle 2 of therapy (after the step-up dosing). CMV viral load was monitored on day 1 of each cycle. We conducted a pooled analysis that included all BsAbs used in MM at our institution (Tec, elra, talq). We assessed the frequencies of grade 3-4 neutropenia (absolute neutrophil count < 1.0× 103/mL), infections, CMV reactivation, and hypogammaglobulinemia.
Results: From 9/1/2023 until 3/31/2024, 142 patients received BsAbs treatment at our institution. Median age for BsAbs was 68 years, 50% were male, 47% were African American, and patients had received a median of 5 prior LOT. 39% of patients had received prior BCMA therapy. Overall, 30% of patients treated with BsAbs experienced an infection during therapy. Of the 142-patients treated 25% had CMV reactivation; no patients were admitted for CMV treatment or complications. Infection rates were lowest in patients treated with taqluetamab (23% all cause infections and 16% CMV reactivation) compared to teclistamab (30% infections and 22% CMV reactivation) and elranatamab (45% infections and 55% CMV reactivation). 60% of patients were receiving concomitant monthly IVIG. Grade 3 neutropenia (ANC < 1000) occurred 57% in patient treated with teclistamab, 44% with taqluetamab and 41% with elranatamab. One patient developed zoster and no patients develop PJP.
Conclusions: In our analysis the prevalence of all grade infections was 30% which is lower than reported in the clinical trials that led to approval of BsAbs for MM. The routine monitoring of CMV allowed for early diagnosis and management resulting in no hospitalizations or death associated with CMV. Under our protocol BsAbs dose frequency was decreased in a treatment response which likely helped with immune reconstitution resulting in fewer infections. The implementation of antimicrobial prophylaxis and IVIG infusions may decrease the risk of infectious complications and should be added to institutional protocols.