Background: The treatment landscape for relapsed/refractory Multiple Myeloma (R/R MM) in Brazil is unique, with both BCMA CAR-T (ciltacabtagene autoleucel, cilta-cel) and bispecific antibodies (teclistamab, talquetamab, elranatamab) being available for patients who are triple class exposed, but without the necessity of a specific number of previous lines of therapy (LoTs). Ciltacel is also approved based on lenalidomide refractoriness and previous proteasome inhibitor exposure. Even though cell therapy is approved, access to it is frequently delayed due to lengthy legal disputes between patients and health insurance, primarily related to insurance coverage. Here, we report demographic and initial safety data for patients treated with cilta-cel.

Methods: We conducted a case series report through chart review of patients with R/R MM treated with cilta-cel at our institution (A.C.Camargo Cancer Center, Sao Paulo, Brazil). All treated patients were included. Baseline clinical and disease characteristics, cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) incidence and grading according to American Society for Transplantation and Cellular Therapy criteria were recorded. Eligibility for CARTITUDE-1 and CARTITUDE-4 was done with available data before apheresis. Brain-to-vein time was measured from cell therapy indication to infusion. Vein-to-vein time was measured from leukapheresis to infusion.

Results: A total of seven patients were included. The majority were male (5/7; 71%), with a median age of 62 years (34–72). The most common ECOG performance status was 0 (4/7) and CARHEMATOTOX score of 1 was also common (3/7). The most common heavy chain type was IgG (4/7; 57%), and the most frequent light chain was kappa (4/7; 57%). The time from initial diagnosis to indication varied considerably, with a median of 3 years (1–17). FISH status was available for only two patients, with both having del17p. For the two patients with 3 or fewer previous lines of therapy (LoTs), one did not fulfill CARTITUDE-4 inclusion/exclusion criteria due to cytopenia, organ dysfunction, and non-secretory disease. Of the other 5 patients, 3 did not fulfill CARTITUDE-1 criteria due to cytopenia (2/3), previous BCMA therapy with teclistamab and belantamab mafodotin (1/3) and non-secretory disease (1/3). All patients were triple class exposed (7/7) and 3 were penta class exposed (3/7). Legal disputes occurred in all cases (7/7). Brain-to-vein time had a median duration of 280 days (195-378). Vein-to-vein had a median duration of 92 days (62-180). Out-of-specification products occurred in 4 patients with different reported reasons: low average of viable cell concentration (1/4), low cell count (2/4), low potency (1/4). One patient had received talquetamab before CART indication. The most common holding therapy was talquetamab (3/7). Bridging therapy was offered in 4/7 patients, with the most common being talquetamab (2/4). Median follow-up after infusion was 127 days (41-183). Response at 30 days was available for only one patient, with a partial response. CRS was frequent (6/7) with all being grade 1 or 2 (7/7). Tocilizumab was commonly used (4/7). ICANS grade 3 occurred in one patient, as did one other event of grade 1 in another patient. One patient progressed and died within less than 6 months of therapy. All other patients were alive at the time of this submission.

Conclusion: Access to CAR-T therapy for multiple myeloma in Brazil is often marked by extensive delays, resulting in a prolonged and complex treatment journey. Most patients wouldn't have fulfilled inclusion/exclusion criteria for the clinical trials the led to ciltacel approval. In this case series, acute toxicity profile for CRS and ICANS was similar to previous reported data.

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2025
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