Prophylaxis and Vaccinations for Infections with BCMA and GPRC5D T-Cell Engagers in Multiple Myeloma: Usmirc Practice Patterns
Authors: Kamboj Ishita , Gorsline Chelsea , Majeed Aneela , Ince Dilek , Snyder Jordan , Shaikh Hira , Khan Abdullah Mohammad , Green Kimberly M , Atrash Shebli , Anwer Faiz , Ryu Tiger Claire Yun Kyoung , Alkharabsheh Omar , Mewawalla Prerna , Abdallah Al-Ola , Paul Barry , Ahmed Nausheen 
Published: December 2024

Introduction: BCMA and GPRC5D T-cell Engagers (TCE) are novel immune effector cell therapies for relapsed/refractory multiple myeloma (RRMM). Despite high efficacy, TCEs pose significant infection risks. Currently, there is limited literature guiding infection prophylaxis (PPx) and monitoring in TCE-recipients. The U.S. Myeloma Innovations Research Collaborative (USMIRC) is a research organization that includes academic, NCI designated, and community cancer centers in the United States. This study surveyed USMIRC participants to gain a better understanding of the infection PPx and assessment practices in BCMA and GPRC5D TCE recipients.

Methods: The questionnaire was developed by a team of physicians specialized in MM, infectious disease, and cellular therapy (BP, CG, NA). It included 6 demographic and 12 PPx related questions. It was electronically distributed to 15 physicians (9 myeloma, 3 infectious disease, 2 cell therapy, and 1 pharmacist) across 9 centers delivering TCEs. Centers were categorized as high volume (initiating &gt;50 TCEs in the last year), mid volume (26-50), or low volume (&lt;25). The survey was completed in July, 2024. Descriptive analysis is reported.

Results: All invited participants responded to the survey. All centers offered both teclistamab and talquetamab, and 7 also used elranatamab. There were 4 high volume, 3 mid volume, and 2 low volume centers. The majority (93.3%) of the respondents checked baseline serum IgG levels with most (73.3%) monitoring them monthly. All (100%) routinely administered intravenous immunoglobulin (IVIG) infusions post TCE therapy: 66.7% initiated at IgG &lt; 400 mg/dL, 20% at IgG&lt; 400 mg/dL with recurrent infections, and 13.3% regardless of IgG levels. Only 53.3% routinely obtained serum CD4 levels during the first year of TCE, with most (62.5%) of those who follow levels monitoring them monthly. Most (73.3%) performed baseline screening for CMV (Cytomegalovirus) viremia but only 26.7% continued routine monitoring. Those not routinely testing for CMV would test based on multiple criteria: positive baseline (46.2%), high-dose steroids initiated (30.8%), steroids used for &gt;7 days (30.8%), and symptoms (15.4%). For CMV-positive cases, the test was repeated at varying frequencies, mostly weekly (71.4%). CMV-directed treatment was initiated based on CMV PCR levels &gt;500 copies/ml (53%) and &gt;1000 copies/ml (27%), while 20% had other criteria.

Only 6.7% of centers routinely used CMV PPx. All centers used HSV/VZV PPx, but timing of initiation varied: 53.3% started PPx pre-TCE therapy and 46.7% at TCE initiation, with discontinuation criteria highly variable. A notable number of respondents (86.6%) employed Pneumocystis jiroveci pneumonia (PJP) PPx. Most (76.9%) started PJP PPx with the onset of TCE and stopped based on CD4 count or discontinuation of TCE. Pseudomonas coverage was used by two-thirds (66.7%) of the respondents and yeast/candida PPx usage was nearly balanced with 47% using it. The criteria for using them was based on ANC levels and neutropenia. Only 6.7% of respondents used mold PPx.

Post-TCE therapy immunizations were recommended at 6 (67%) institutions. The recommended vaccinations varied, although most institutions recommended: Influenza (80%), SARS-CoV-2 (COVID-19) (80%) and Respiratory syncytial virus (RSV) (73%). Other vaccines were used less frequently: Prevnar 20 (33%), Pentavalent (DPT, Hep B, H.influenzae) (27%), Hep B virus (27%), RZV (27%), MCV4 (20%), Pneumovax 23 (20%), HPV (20%), MMR live (20%) and VZV live (6%). Influenza vaccines were typically given between days 31-90, COVID-19 and RSV vaccines around day 90.

Conclusion: Our survey revealed variable practices for infection PPx and vaccinations. HSV/VZV PPx and monitoring of IgG levels was done unanimously, PJP PPx and primary PPx of infections with IVIG replacement were commonly used; however, CD4 monitoring, CMV monitoring and use of non-seasonal vaccination practices were heterogeneous. PPx practices showed significant variability with regards to use of fungal and pseudomonas coverage during neutropenic periods. While there are limitations in the generalizability of these practices, these findings demonstrate several areas with varying clinical practices across USMIRC centers. Further studies are needed to correlate these practices with infection rates and to allow development of consensus guidelines for both academic and community centers.