Early Treatment Failure in Patients Receiving Ciltacabtagene-Autoleucel for Relapsed/Refractory Multiple Myeloma

Area of Science:

• Hematology
• Oncology
• Immunotherapy

Background:

• Ciltacabtagene autoleucel (cilta-cel) offers significant efficacy in relapsed/refractory multiple myeloma (RRMM).
• A subset of patients treated with cilta-cel experiences early treatment failure, necessitating investigation into predictive factors.
• Understanding these factors is crucial for optimizing patient selection and management strategies.

Purpose of the Study:

• To identify pretreatment clinical factors associated with early progression or death within 12 months in RRMM patients receiving standard-of-care cilta-cel.
• To evaluate the impact of early treatment line utilization on progression-free survival (PFS).
• To assess the predictive value of measurable residual disease (MRD) and FDG PET/CT response for early treatment failure.

Main Methods:

• Retrospective analysis of RRMM patients treated with cilta-cel at three Mayo Clinic centers.
• Inclusion criteria: follow-up of at least 12 months or progression/death within 12 months.
• Statistical analysis to identify independent predictors of early progression or death, including pretreatment factors, MRD status, and PET/CT response.

Main Results:

• Early treatment failure (n=52) comprised 69% progressive disease and 31% non-relapse mortality (NRM).
• Independent predictors of early progression or death included prior BCMA-directed therapy, extramedullary disease, and CAR-HEMATOTOX score ≥ 2.
• Measurable residual disease positivity at 3 months (OR 5.68) and suboptimal FDG PET/CT response at 3 months (OR 11.8) were associated with increased early treatment failure risk.

Conclusions:

• Prior BCMA therapy, extramedullary disease, and CAR-HEMATOTOX score are key predictors of early cilta-cel failure in RRMM.
• MRD positivity and incomplete FDG PET/CT response at 3 months identify high-risk patients for early adverse outcomes.
• Findings support the need for novel therapeutic strategies for high-risk patients identified through these predictive markers.