Functionally high-risk disease is associated with poor outcomes after late-line CAR T-cell therapy for multiple myeloma

While CAR T has shown superior efficacy in earlier line of therapy [1, 2] for functionally high-risk multiple myeloma (FHRMM), outcomes with its use in later lines (3+) for FHR disease remain unknown. We describe a single-center experience of FHRMM patients (pts), defined as those with progression of disease (POD) < 24 months of frontline therapy, receiving CAR T-cell therapy. Of the 208 pts treated with CAR T, 117 (56%) had FHR disease and had received median of 5 prior lines of therapy (LOT). FHR pts had higher rates of extramedullary disease (EMD) and progression within 12 months of transplant. Median PFS were 11 and 13 months (p = 0.15), and median OS were 34 and 55 months (p = 0.025) in the FHR and non-FHR groups, respectively. On multivariable analyses, EMD and high disease burden were associated with inferior OS. FHRMM pts receiving CAR T as late LOT had inferior survival outcomes compared to those with non-FHR disease, underscoring the poor prognostic impact of POD < 24 months from frontline therapy. This association was largely driven by active EMD and high disease burden at the time of CAR T, highlighting the potential benefit of utilizing CAR T as an early LOT for FHRMM.

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Publication Details

Journal
Blood Cancer Journal
Published
2026-04-12
DOI
https://doi.org/10.1038/s41408-026-01494-y
Primary Topic
CAR-T cell therapy research
Type
article
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article

Functionally high-risk disease is associated with poor outcomes after late-line CAR T-cell therapy for multiple myeloma

Heather Jolie Landau, Kylee H. Maclachlan, Hamza Hashmi, Saad Z. Usmani et al.
Blood Cancer Journal
CAR-T cell therapy research
article

Functionally high-risk disease is associated with poor outcomes after late-line CAR T-cell therapy for multiple myeloma

Heather Jolie Landau, Kylee H. Maclachlan, Hamza Hashmi, Saad Z. Usmani, Malin L. Hultcrantz, Tasmin Farzana, Gunjan L. Shah, Alexander M. Lesokhin, Hani Hassoun, Eric Matthew Jurgens, Sham Mailankody, Neha Korde, Sridevi Rajeeve, Sergio A. Giralt, David Nemirovsky, Andriy Derkach, Tara Sebastian, Carlyn Rose C. Tan, Ross Firestone, Francesco Maura, Michael Scordo, Urvi A. Shah, Kevin C. Miller
article en

Abstract

While CAR T has shown superior efficacy in earlier line of therapy [1, 2] for functionally high-risk multiple myeloma (FHRMM), outcomes with its use in later lines (3+) for FHR disease remain unknown. We describe a single-center experience of FHRMM patients (pts), defined as those with progression of disease (POD) < 24 months of frontline therapy, receiving CAR T-cell therapy. Of the 208 pts treated with CAR T, 117 (56%) had FHR disease and had received median of 5 prior lines of therapy (LOT). FHR pts had higher rates of extramedullary disease (EMD) and progression within 12 months of transplant. Median PFS were 11 and 13 months (p = 0.15), and median OS were 34 and 55 months (p = 0.025) in the FHR and non-FHR groups, respectively. On multivariable analyses, EMD and high disease burden were associated with inferior OS. FHRMM pts receiving CAR T as late LOT had inferior survival outcomes compared to those with non-FHR disease, underscoring the poor prognostic impact of POD < 24 months from frontline therapy. This association was largely driven by active EMD and high disease burden at the time of CAR T, highlighting the potential benefit of utilizing CAR T as an early LOT for FHRMM.

Blood Cancer Journal
Memorial Sloan Kettering Cancer Center (US)
No poverty
Openalex Percentile: Top 25%
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
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