Effects of Intravenous Immunoglobulin Supplementation (IVIG) on Infections in Recipients of Teclistamab Therapy for Multiple Myeloma (MM): A Multi-Institutional Study
Authors: Cheruvalath Heloise , Clennon Anna , Shrestha Asis , Szabo Aniko , Bhatlapenumarthi Vineel , Patwari Anannya , Balev Metodi , Bhutani Divaya , Thanendrarajan Sharmilan , Dhakal Binod , Zangari Maurizio , Trikannad Anup Kumar , Vellanki Sruthi , Al Hadidi Samer , Lentzsch Suzanne , van Rhee Frits , Shah Mansi R. , Bag Aishee , D'Souza Anita , Chakraborty Rajshekhar , Shah Nishi , Schinke Carolina , Mohan Meera 
Published: December 2024

Introduction: While IVIG supplementation has been shown to prevent high-grade infectious complications, there is lack of clear consensus on the optimal timing of initiation of IVIG in the context of teclistamab for MM. In this multi-institutional study, we report the effect of IVIG supplementation on infectious complications in recipients of teclistamab.
Methods: All consecutive patients with MM treated with at least one dose of standard-of-care teclistamab at 4 academic centers in the US were included in this study. Infection prophylaxis was at the discretion of the treating physician. Primary IVIG prophylaxis was defined as administering IVIG within the first 60 days of starting the teclistamab or any time before the first documented infection. Secondary IVIG prophylaxis was defined as IVIG administration before the start of teclistamab. For this analysis, patients who were started on IVIG after a documented infection were included in the “no IVIG prophylaxis” group. Data including patient demographics, disease, and treatment characteristics were retrospectively collected. Infection data was collected upto 60 days after the last dose of teclistamab.
Results: A total of 168 patients with a median follow up of 8.5 months were included in this analysis. The median age was 70 (range 31-89) years with 49% (n=82) of patients ≥70 years of age. About 25% (n=42) of patients were African Americans. The median number of prior lines of therapy was 5 (range 1-12) with 52% (n=88) of patients having penta-class refractory MM. Majority of patients (95%, n=160) had at least one prior ASCT. A third of the patients had a prior BCMA directed therapy, mostly CAR T cell therapy. The median duration of teclistamab therapy was 4.6 months and median doses of teclistamab was 15. While all patients received herpes zoster prophylaxis, 73% (n=122) of patients were on primary PJP prophylaxis. Forty-two % (n=71) of patients received IVIG, with majority being primary IVIG prophylaxis (n=63). Most common dosing schedule for IVIG was 0.4mg/kg every 4 weeks. In this context, 181 infections were recorded in 92 patients. 53% of the infections were bacterial infection occurring in 61 patients. 42% of infections were viral occurring in 52 patients. There were 9 fungal infections in 7 patients. Among this, 55% were ≥ grade 3 with 57% of these events requiring inpatient hospitalization. The 3-month cumulative incidence of all grade infection was 43% (95% CI 36%-52%) and ≥ grade 3 infection was 23% (95% CI 18%-31%). Further, the 3-month cumulative incidence of all grade infection in patients who did not receive IVIG, patients on primary and secondary IVIG prophylaxis were 49% (95% CI 39%-61%), 36% (95% CI 26%-50%) and 38% (95% CI 15%-92%), respectively; Gray's test p= 0.24. The 3-month cumulative incidence of ≥ grade 3 infection in recipients of primary IVIG prophylaxis was 9.8% (95% CI 4.6%-21%) compared to 38% (95% CI 15%-92%) and 32% (95% CI 23%-43%) in patients receiving secondary IVIG prophylaxis and no IVIG, respectively; Gray's test p= 0.014. Cox regression modeling compared different interval since last dose of IVIG. Compared to not having had IVIG, having had the latest one within the past 30 days lowers the hazard of infection 0.59-fold (p=0.018) in a univariate analysis. Having had the latest one within 30-60 days, or &gt; 61+ days ago has similar hazard ratio (HR), but does not reach statistical significance. The effects of IVIG are stronger for bacterial infections at earlier time points (HR-0.42, 95% CI 0.23,0.77; p=0.005) compared to later time points of 31-60 days and &gt;60 days. Timing of IVIG therapy did not influence the incidence of viral infections. Other factors associated with increased risk of infection on multi-variate analysis included use of tocilizumab for CRS (HR-1.54, 95% CI 1.07, 2.21; p=0.019) and number of prior infections (HR-1.30, 95% CI 1.14,1.50; p=&lt;0.001). Cost effectiveness analysis is being done and will be updated at the meeting.
Conclusion: Primary IVIG supplementation reduces the risk of high-grade infections in patients receiving teclistamab therapy. IVIG administration within the past 30 days may lower the risk of high-grade and bacterial infections. Future studies are necessary to identify patients at highest risk of infections, allowing for more targeted IVIG therapy adjustments.
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