Key Clinical Summary:

• Design/Population: A CIBMTR registry analysis evaluated > 800 patients with relapsed/refractory multiple myeloma treated with a homogeneous BCMA-directed CAR T-cell construct, assessing infection incidence, risk factors, and survival with landmark analyses at day 100.
• Key Outcomes: Cumulative infection incidence by day 100 was ~27 to 28% overall (viral 14.4%, bacterial 14.1%, fungal ~3%). Bacterial infections decreased after day 30, while viral infections continued to increase beyond day 30. Infection-related mortality was low (1.1%); NRM 1.8% at day 100. Risk factors for infection included higher-grade CRS/ICANS, Karnofsky <80, and prior infections. ≥ 2 infections within 100 days were associated with inferior OS (HR ~2.4). IVIG replacement was associated with improved OS (HR ~0.5).
• Clinical Relevance: In BCMA CAR T-treated myeloma, viral infections predominate late, contrasting with CD19 CAR-T experience. These data support risk-adapted, pathogen-specific prophylaxis and monitoring, highlight the prognostic impact of early recurrent infections, and suggest a potential survival benefit of IVIG replacement to inform post-CAR T supportive care guidelines.

Bilal Abid MD, MS, FACP, MRCP, FRCP, Texas Tech University Health Sciences Center, Lubbock, Texas, presented results from a large CIBMTR registry analysis of patients with relapsed/refractory (R/R) multiple myeloma (MM) treated with BCMA-targeted CAR T-cell therapy, focusing on infection patterns and outcomes.

These results were presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.

The results showed that while overall infection rates declined after the first 30 days, viral infections continued to increase, with infections occurring in nearly 28% of patients by day 100, though infection-related mortality remained low. 

Dr Abid concluded, “this allows societies and committees and regulatory bodies to generate guidelines which are risk adapted, pathogen specific and sort of duration specific.”

Transcript:

I am Bilal Abid and I represent the western half of Texas. I come from the Texas Tech University Health Science Center. Thank you for having me.

We presented data from our CIBMTR registry analysis in which we looked at infections in BCMA-targeted CAR T-cell therapy in patients with underlying relapsed and refractory multiple myeloma. The premise of the study is, background, that we have significant data on infections and immune reconstitution with CD19-directed CAR T-cells, both in leukemia and in lymphoma. However, data is almost nonexistent when it comes to BCMA-targeted CAR T-cells in myeloma—with the data that's out there either is out of clinical trials or single center small studies.

We wanted to look at that more systematically. To do that, we leveraged the large CIBMTR registry database and included over 800 patients with a homogenous CAR construct and an underlying disease of relapsed/refractory multiple myeloma. We looked at baseline characteristics and we looked at those very carefully. Then we designed models to do landmark analysis of overall survival and progression-free survival at day 100. Also did multivariate analysis to identify risk factors for infections and then see what types of infections and disease characteristics are conferring survival advantage or disadvantage.

Key takeaway from the study include that in about 807 patients we saw an infection density, overall infection density, really decreasing from within the first 30 days to day 30 and beyond. That was paradoxical when we stratify between bacterial and viral infection. Bacterial infection density actually decreased from within the first 30 days to day 30 and beyond. However, viral infections actually continued to increase beyond day 30 and that's 1 of the key findings.

The other thing was that cumulative incidence of infections at day 100 was about 27-28% for overall infections, 14.4% for viral infections, 14.1% for bacterial infections and nearly about 3% for fungal infection. Again, viral infections predominating in the BCMA myeloma space. Infection-related mortality was low at 1.1%, which was a function of non-relapse mortality, which was 1.8% at day 100.

Now in terms of identification for risk factors and drivers for infection on multivariate analysis, we identified higher grade CRS, higher grade ICANS, substandard Karnofsky Performance score less than 80 to be precise, and prior infection history to be driving infections within the first 100 days.

Now, landmark analysis for overall survival showed that we identified 4 key factors which conferred mortality benefit or overall survival disadvantage. One of the ones was presence of external adultery disease or plasma cell leukemia. Prior BCMA exposure and prior infection were significantly associated with inferior overall survival. Now in particular, if someone had 2 or more infection episodes in the first 100 days of CAR infusion, had nearly 2 and a half times lower survival. Overall survival beyond 100 days post-CAR infusion hazardous ratio was about 2.4, a statistically significant result.

One thing that did stand out in the middle of doom and gloom, something that stuck out as a positive ray of hope was [intravenous immunoglobulin] (IVIG) replacement. That conferred a survival advantage. Overall survival hazardous ratio was 0.5. IVIG replacement post-BCMA CAR infusion is beneficial and confers a survival advantage. Now there is a limitation that CIBMTR does not capture IVIG data in terms of timing, dosing, formulation, post-CAR-T infusion, but this did pan out. This did read out to be significant there.

To conclude, in this large registry analysis, we take away 2 things. One, we develop baseline infection burden in this cohort of patients. We are seeing at this ASH that myeloma cell therapy landscape has just expanded rapidly. We saw 2 new CAR constructs coming into the pipeline and reading out very nicely in early data. This was important to be able to generate baseline infection of risk and burden. Then secondly, we also identified that viral infections are predominant, which is sort of in contrast to CD19 because this allows societies and committees and regulatory bodies to generate guidelines which are risk-adapted, pathogen-specific and sort of duration-specific. Thank you for having me.

Source:

Abid MB, Wudhikarn K, Ye Q, et al. Infections in patients with relapsed refractory multiple myeloma receiving idecabtagene vicleucel therapy: A real-world analysis from CIBMTR. Dec 6-9, 2025; Orlando, FL. Abstract: 716