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
Mené aux Etats-Unis sur 78 patients atteints d'un myélome multiple récidivant ou réfractaire (durée médiane de suivi : 16,9 mois), cet essai de phase IB/II évalue l'intérêt, du point de vue de la qualité de vie déclarée par les patients, du ciltacabtagène autoleucel (une immunothérapie à base de lymphocytes CAR-T ciblant l'antigène de maturation des cellules B)
Background : CARTITUDE-1 is a phase 1b–2 study evaluating ciltacabtagene autoleucel (cilta-cel),a chimeric antigen receptor T cell therapy with two B-cell maturation antigen–targetingsingle-domain antibodies, in patients with relapsed or refractory multiple myeloma.Primary efficacy outcomes have previously been reported. Here, we report health-relatedquality of life (HRQOL) secondary outcomes evaluated using patient-reported outcomes. Methods : This single-arm, open-label, phwase 1b–2 study was done at 16 centres in the USA.Patients were aged 18 years or older with diagnosis of multiple myeloma and EasternCooperative Oncology Group performance status of 1 or less with three or more previouslines of therapy, or were double refractory to a proteasome inhibitor and immunomodulatorydrug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR+ T cells per kg) was administered 5–7 days after lymphodepletion. Patient-reportedoutcomes were assessed using the European Organisation for Research and Treatmentof Cancer (EORTC) quality of life questionnaire core 30-item, pre-specified itemsfrom the EORTC myeloma module, and EuroQol five-dimensional descriptive system questionnaire.Clinically meaningful changes in patient-reported outcomes were defined by anchor-basedminimally important differences. This trial is registered with ClinicalTrials.gov, NCT03548207. This trial is completed but feeding into a long-term follow-up study. Findings : Between July 16, 2018, and Oct 7, 2019, 78 patients were enrolled and underwent apheresis in phase 2 of the study. 68 patients were treated (43 [63%] male, 49 [72%] White),and their patient-reported outcomes assessed (median follow-up 16·9 months, IQR 15·7–17·5).After infusion, a transient decline was observed, followed by improvements in globalhealth status (mean change from baseline to day 464 +8·0 points, SD 20·9), physical(+4·6 points, 21·1), and emotional functional scales (+1·9 points, 23·7) over time,and declines for symptom-based scores (−14·1 pain, SD 31·5 and –15·4 fatigue; SD 29·5),indicating improved patient HRQOL following treatment with cilta-cel. Interpretation : These durable HRQOL improvements are consistent with clinical findings, in which asingle cilta-cel infusion led to substantial and durable responses in heavily pre-treatedpatients with relapsed or refractory multiple myeloma. These results support the useof cilta-cel in patients with relapsed or refractory multiple myeloma.