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

Introduction: Despite the high efficacy of BCMA directed Chimeric Antigen Receptor T-cell Therapy (CART) in relapsed/refractory multiple myeloma (RRMM), there are significant infection risks. Monitoring and management of infections in CART-recipients may vary. The U.S. Myeloma Innovations Research Collaborative (USMIRC) is a research organization that includes academic, NCI-designated, and community cancer centers in the USA. This study surveyed USMIRC participants to assess infection PPx and assessment practices in CART 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 14 providers (8 myeloma, 3 infectious disease, 2 cell therapy and 1 pharmacist) across 8 centers delivering CART. 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 including responses to open-ended questions.

Results: All invited participants responded to the survey. All 8 centers offered ide-cel while cilta-cel was offered by 6. There were 2 high volume, 2 mid volume and 4 low volume centers. All respondents checked baseline serum IgG levels and routinely monitored them: monthly (78.57%), at the start of cycle (14.28%) and every 3 months (7.14%). Intravenous immunoglobulin (IVIG) infusion post-CART therapy was consistent among all (100%), with 85.72% initiated at IgG &lt; 400 mg/dL. Serum CD4 levels were routinely obtained during the first year of CART by 71.5% respondents, with most (70%) of those who follow levels monitoring them monthly. A considerable number of respondents (78.6%) did baseline screening for CMV (Cytomegalovirus) viremia but only 35.7% continued routine monitoring. For CMV-positive cases, the test was repeated at varying frequencies, mostly weekly (71.42%). CMV-directed treatment was initiated based on CMV PCR levels &gt;500 copies/ml (50%) and &gt;1000 copies/ml (29%), while 21% had other criteria.

None of the centers routinely used CMV PPx, whereas all (100%) centers used Pneumocystis jiroveci pneumonia (PJP) PPx. Most (78.5%) began PJP PPx simultaneously with the onset of CART or at day 30. Most discontinued PPx when CD4 count was&gt; 200 cells/µL (71.4%) or at 6 months (28.6%). The majority (92.8%) used HSV/VZV and pseudomonas PPx. The timing of HSV/VZV PPx initiation varied among respondents: 38.5% starting PPx prior CART infusion and 61.5% during CART initiation. Pseudomonas coverage was used for neutropenia; however, absolute neutrophil count (ANC) levels threshold for initiation varied (15.4% used &lt;500 cells/µL, 15.4% used &lt;1000 cells/µL, 7.7% used &lt;100 cells/µL, others did not specify). Two-thirds (64.3%) of respondents used yeast/candida PPx; however, ANC threshold for initiation varied (33.3% used &lt;500 cells/µL, 22.2% used &lt;100 cells/µL, 11.1% used &lt;100 cells/µL, others did not specify). The majority did not use mold PPx, except for 14.3% who used it for prolonged immunosuppression or with history of marijuana use.

Post CART therapy immunizations were recommended at 5 institutions. Vaccinations for respiratory viral infections were consistently recommended. Other vaccines were given less frequently with Prevnar 20 at 64.3%, Pentavalent (DPT, Hep B, H. influenzae) at 57%, Hep B virus (HBV), RZV, and MCV4 each at 50%. Pneumovax 23 and MMR (live) were recommended by 42.8%, HPV by 35.7%, and VZV (live) by 21.4%.

Conclusion: Our survey revealed that post BCMA CAR-T, monitoring of IgG levels was unanimous, whereas CD4 and CMV monitoring was heterogeneous. While there was consistency in the use of prophylaxis for pseudomonas, PJP, and other fungal infections, ANC thresholds to initiate did vary. Moreover, mold prophylaxis was notably underutilized. Vaccination practices for non-respiratory viral infections varied, with the least recommended vaccine being MMR. While there are limitations in the generalizability of these practices, these findings demonstrate marked differences in clinical practices across USMIRC centers. Further studies are needed to correlate these practices with downstream infection rates and to allow the development of consensus guidelines for both higher and lower-volume centers.