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Treatment with CAR T-Cell Therapy vs. TCEs Less Important Than Achieving MRD for Patients with R/R MM

December 19, 2023

January 2024

Leah Lawrence

Leah Lawrence is a freelance health writer and editor based in Delaware.

Achievement of measurable residual disease (MRD) negativity resulted in prolonged survival among patients with relapsed or refractory (R/R) multiple myeloma (MM), regardless of whether they were treated with chimeric antigen receptor (CAR) T-cell therapy or T-cell engagers (TCEs), according to a study presented at the 65th American Society of Hematology Annual Meeting and Exposition in San Diego.

Study presenter Aintzane Zabaleta, PhD, of Instituto de Investigación Sanitaria de Navarra in Pamplona, Spain, pointed out that “while MRD-negative rates were superior in those eligible for CAR T-cells versus TCEs, the impact of achieving MRD negativity on patients’ survival was similar in both settings.”

Existing data have shown the association between MRD negativity and improved outcomes in patients with newly diagnosed and R/R MM. However, no previous studies of this association included patients treated with newer therapies such as CAR T-cell therapy and TCEs.

Dr. Zabaleta and colleagues studied data from 125 patients with R/R MM treated with CAR T-cell therapy and 144 treated with TCEs between November 2017 and February 2023. Median follow-up was 11 months.

MRD assessed in the bone marrow was available for 190 of the 269 included patients. Any patient without assessment was considered MRD positive in the intent-to-treat analyses. Median progression-free survival (PFS) was nine months, and median overall survival (OS) was 23 months.

Patients who were MRD negative had significantly improved median PFS (20 months vs. 3 months, respectively; p<0.001) and median OS (not reached vs. 7 months, respectively; p<0.001) compared with those who were MRD positive. MRD negativity was associated with an 88% reduction in the risk of progression and/or death (hazard ratio = 0.12; 95% CI 0.085-0.17; p<0.001).

Additionally, patients who had sustained MRD negativity had improved PFS compared with those who converted from MRD negative to MRD positive and those who were MRD positive.

“Among those patients achieving MRD negativity, the median PFS was exactly the same, regardless of the immunotherapy they received,” Dr. Zabaleta said. Median PFS for both was 20 months.

There was a higher rate of MRD negativity among patients treated with CAR T-cell therapy compared with TCEs. These higher rates were observed with CAR T-cell therapy at six-, 12-, and 24-month landmark analyses.

In a multivariate analysis, Dr. Zabaleta and colleagues found that depth of response (complete response [CR] or better) and MRD negativity were relevant prognostic factors and “could be considered as a treatment endpoint in this setting.” Patients who achieved both CR and MRD negativity had the best outcomes; however, not achieving one or the other was associated with inferior outcomes.

According to Dr. Zabaleta, this indicated that achieving CR does matter in patients with MRD-negative R/R MM with respect to durability after treatment with CAR T-cell therapy or TCEs.

Any conflicts of interest declared by the authors can be found in the original abstract.

Reference

Zabaleta A, Puig N, Romero MTC, et al. Clinical significance of measurable residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) patients (Pts) treated with chimeric antigen receptor (CAR) T cells and T-cell engagers (TCE). Abstract 94. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 9, 2023; San Diego, California.

 

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