Feasibility of anti-BCMA CAR-T therapy in a middle-income country Free

Ciltacabtagene autoleucel (cilta-cel) was approved in Brazil in April 2024 and is currently the only BCMA-directed CAR-T product available for the treatment of relapsed/refractory multiple myeloma (R/R MM). Due to its unique label, the therapy can be prescribed to triple-class–exposed patients regardless of the number of prior lines of therapy (LoTs), as well as to those who have received proteasome inhibitors and are refractory to lenalidomide. The high cost of therapy may be more relevant in middle-income countries compared to the developed world. Access to cell therapy is often delayed due to denial of coverage by insurance companies, which may impact optimal treatment outcomes. Legal disputes between patients and insurers frequently precede treatment approval. Here, we report demographic and feasibility data for patients for whom cilta-cel was indicated. Methods: We conducted a chart review study of patients with R/R MM for whom cilta-cel was indicated at our institution (A.C.Camargo Cancer Center, São Paulo, Brazil) from April 2024 to July 2025. All patients evaluated during this period were included. We evaluated baseline characteristics, including demographics, cytogenetic risk, prior LoTs, exposure status, eligibility for CARTITUDE-1 (for patients with ≥4 prior LoTs) and CARTITUDE-4 (for those with 1–3 prior LoTs). We investigated outcomes during the CAR-T journey, including holding and bridging therapies and two exploratory outcomes: “brain-to-nowhere” and “delayed access interval.” The brain-to-nowhere interval was defined as the time from cell therapy indication to the next line of therapy (without immediate CAR-T intent), spontaneous dropout from the CAR-T journey, loss to follow-up, or death — whichever occurred first — and patients who underwent apheresis were excluded. The delayed access interval was defined as the time from cell therapy indication to last follow-up without insurance approval, first apheresis, next line of therapy (without CAR-T intent), spontaneous dropout, loss to follow-up, or death — whichever occurred first. Results: A total of 35 patients were included. The majority were male (22/35, 62%) with a mean age of 60 years (range 34–75, SD 11.4). Most had IgG (19/35, 54%) and kappa (19/35, 57%) R/R MM. Time from diagnosis to indication varied, median 3 years (1–17). FISH data were unavailable for 68% (24/35). Deletion 17p was the most frequent identifiable cytogenetic abnormality (5/11). The median number of prior LoTs was 3 (range: 1–10). All patients were triple-class exposed (35/35); 28% (10/35) were penta-drug exposed. Six patients had prior talquetamab (not considered holding/bridging), and three had prior anti-BCMA therapy (not CAR-T). Among 21 patients with up to 3 LoTs, 33% (7/21) would not have fulfilled CARTITUDE-4 eligibility; data were missing for 10. Causes included cytopenia (3/7), nonsecretory/oligosecretory disease (2/7), renal dysfunction (1/7), other organ dysfunction (1/7), ECOG >1 (1/7), and lack of lenalidomide refractoriness (1/7). More than one cause was identified in one patient. Among 14 patients with ≥4 LoTs, 50% (7/14) would not have fulfilled CARTITUDE-1 eligibility; data were insufficient for two. Causes included cytopenia (5/7), prior anti-BCMA therapy (3/7), ECOG >1 (3/7), renal dysfunction (1/7), nonsecretory/oligosecretory disease (1/7), and prior malignancy (1/7). Four had multiple causes. Only two patients had their CAR-T therapy authorized by insurance without legal action. Holding therapy was confirmed in 57% (20/35), with the most common being talquetamab (7/20), followed by pomalidomide-based (6/20), and carfilzomib-based (6/20); three patients received more than one holding regimen. Ten patients underwent apheresis, with seven ultimately receiving cilta-cel; one patient died during manufacturing. Median brain-to-nowhere was 115 days (17–444): five patients died while awaiting approval, four dropped out, two were lost to follow-up, and one switched to teclistamab. Median delayed access interval was 115 days (16–443), with 13 patients still pursuing CAR-T. Conclusion: Treatment of R/R MM with anti-BCMA CAR-T in Brazil is challenging due to unprecedented delays, primarily related to limited access. Most evaluable patients would not have met the eligibility criteria of the clinical trials that supported cilta-cel approval. This study highlights the urgent need for optimization of access pathways for eligible patients.