Even with novel therapeutic advances, health-related quality of life (HRQOL) in patients with relapsed/refractory multiple myeloma (RRMM) deteriorates with each successive line of therapy. Patients with RRMM have a poor prognosis with limited treatment options, so consideration of a patient’s HRQOL should be evaluated in addition to clinical outcomes. Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy with 2 B-cell maturation antigen (BCMA)-targeting single-domain antibodies. It has demonstrated efficacy in patients with RRMM and was FDA approved in February 2022 for adults with RRMM who had ≥4 previous lines of therapy. CARTITUDE-1 was a single-arm, open-label, phase 1b-2 study investigating the safety and efficacy of cilta-cel, and a recent publication by Martin and colleagues reported on HRQOL as a secondary outcome using patient-reported metrics in the phase 2 portion of CARTITUDE-1.
In all, 78 patients were enrolled from July 2018 to October 2019 at 16 centers in the United States. After apheresis, 7 patients discontinued; 71 patients underwent lymphodepletion, and 3 additional patients withdrew before cilta-cel treatment. Patient reported-outcomes were assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire core 30-item version 3 (EORTC QLQ-C30 version 3), 4 single items from the EORTC QLQ myeloma module (MY20; items 44, 48-50), and the EuroQol five-dimensional descriptive system (EQ-5D-5L) questionnaire.
In total, 68 patients received cilta-cel treatment, with a median of 6 previous lines of therapy and a median follow-up of 16.9 months. After a brief and transient decline at day 7, EORTC QLQ-C30 global health status and physical functioning scores showed improvement over time when comparing baseline and day 464. Pain and fatigue symptoms scale scores decreased over the same time period, indicating improvement in these measures as well. Similarly, EORTC QLQ-MY20 scores showed improvements in emotional health status at days 100 and 464 compared with baseline. Out of 49 patient responses at day 100, 25% showed clinically meaningful improvements in restlessness or agitation, 55% had improvements in thinking about illness, 45% showed improvements in worrying about dying, and 35% showed improvements in worrying about their future health. Similar trends were observed with an increase from baseline using the EQ-5D-5L utility score. Across scales, 44% to 62% of patients had improvements in HRQOL, occurring approximately 1 to 3 months after cilta-cel infusion. Initial decline in patient scores was postulated to correspond to onset of cytokine-release syndrome, a relatively common adverse event experienced by patients receiving CAR-T treatment.
In summary, after an initial decline, improvements were seen across physical, emotional, and functioning scales. Heavily pretreated patients with RRMM showed improvements in HRQOL with cilta-cel treatment, and results were consistent with clinical findings that demonstrated durable responses with cilta-cel infusion.
Source: Martin T, Lin Y, Agha M, et al. Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b-2, open-label study. Lancet Haematol. 2022 Oct 7. Epub ahead of print.