A single infusion of ciltacabtagene autoleucel (cilta-cel) resulted in durable improvements in health-related quality of life (HRQoL) in heavily pretreated patients with relapsed or refractory multiple myeloma, according to research published in Lancet Haematology.

The findings come from CARTITUDE-1, a single-arm, open-label, phase 1b/2 study evaluating the chimeric antigen receptor (CAR) T-cell therapy cilta-cel in patients with relapsed or refractory multiple myeloma (ClinicalTrials.gov Identifier: NCT03548207). Researchers reported HRQoL secondary outcomes evaluated using patient-reported outcomes.

Eligibility criteria included age ≥18 years, diagnosis of multiple myeloma, and Eastern Cooperative Oncology Group performance status ≤1, and ≥3 previous lines of therapy, or double refractory to a proteasome inhibitor and immunomodulatory drug and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody.


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In phase 2 of the study, patients received a single cilta-cel infusion (target dose, 0.75×10⁶ CAR+ T cells/kg) 5-7 days after lymphodepletion. The researchers assessed patient-reported outcomes using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30-item, prespecified items from the EORTC myeloma module, and EuroQol 5-dimensional descriptive system questionnaire. They defined clinically meaningful changes in patient-reported outcomes by anchor-based minimally important differences.

A total of 78 patients participated in phase 2 of the study. Of those, 68 patients were treated (men, 63%; women, 37%) and assessed for patient-reported outcomes. The median patient age was 62.0 years (interquartile range [IQR], 55-70), and most patients (72%) were White. The median number of prior therapies for multiple myeloma was 6 (IQR, 4-8). The median follow-up duration was 16.9 months (IQR, 15.7-17.5).

Following infusion, the researchers observed transient declines on day 7 in global health status and physical functioning, role functioning, social functioning, fatigue, and nausea or vomiting. They attributed these findings to the potential onset of cilta-cel adverse events associated with cytokine release.

From baseline to day 464, the team observed improvements in global health status (mean change ± standard deviation, +8.0±20.9 points), physical (mean change ± SD, +4.6±21.1 points), and emotional functional scales (mean change ± SD, +1.9±23.7 points) and declines in symptom-based scores (pain: mean change ± SD, -14.1±31.5 points; fatigue: -15.4±29.5).

“Preservation or improvement of HRQoL is a key outcome, in addition to safety and efficacy, when evaluating treatment regimens for patients with multiple myeloma,” the investigators explained in their report. “We observed durable HRQoL improvements after a single infusion of cilta-cel in heavily pre-treated patients, which are not typically observed in this population with advanced disease. This result might be associated with the clinical efficacy and long treatment-free period afforded by treatment.”

Limitations of the study included the smaller sample size for patient-reported outcomes in phase 2 relative to phase 1b of the study, absence of a comparator group in the single-arm trial, potential issues regarding multiple comparisons, incomplete questionnaires for some patients, and limitation of the analysis to only 4 preselected items from the EORTC QLQ-MY20 to assess the emotional health state of patients.

Disclosure: This research was supported by Janssen Research & Development and Legend

Biotech USA. Please see the original reference for a full list of disclosures.

Reference

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. Published online October 7, 2022. doi:10.1016/S2352-3026(22)00284-8