Outcomes of Outpatient Administration of Ciltacabtagene Autoleucel (Cilta-cel) in Relapsed Refractory Multiple Myeloma (RRMM)

Introduction

Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell (CAR-T) therapy, is approved for treating relapsed or refractory multiple myeloma patients who have received at least one prior line of therapy. As with other CAR-T treatments, it is typically administered in an inpatient setting, followed by close monitoring of patients at the treatment center for several weeks to manage serious adverse events (AEs) such as cytokine release syndrome (CRS) and neurotoxicity. There is however increasing interest in outpatient administration of cilta-cel with the aim to reduce healthcare costs and improve patient quality of life (QoL). This review aims to assess whether outpatient administration yields comparable outcomes to the traditional inpatient setting.

Methods

A systematic literature review was conducted, in accordance with PRISMA guidelines, in MEDLINE, Embase and Cochrane Library and conference proceedings through May 25, 2024 to identify literature on outpatient and inpatient use of cilta-cel in patients with multiple myeloma. Data related to efficacy outcomes (overall response rate [ORR], progression-free survival [PFS], overall survival [OS]), safety outcomes, healthcare resource use and related costs, and patient quality-of-life outcomes, were extracted from the shortlisted publications, collated and qualitatively synthesized. No restrictions were applied on study type or geography. Retrieved records were screened for eligibility by two reviewers independently against pre-defined PICOS criteria, and any disagreements were resolved by a third investigator.

Results

40 unique publications, based on 5 clinical trials (9 sub-studies), 11 observational studies, 5 economic evaluations, and 1 physician survey, were included for data synthesis. Three studies, all real-world observational in nature, involved cilta-cel administration in the outpatient setting - Waqar et al. included both inpatient (N=6) and outpatient (N=27) settings and reported outcomes separately; Gregory et al. involved both settings (N=57; 37 outpatient, 20 inpatient) but reported only consolidated outcomes; Ly et al. involved only the outpatient setting (N=24). All other studies were based on cilta-cel administration in an inpatient setting, with the exception of 2 patients out of a total of 372 patients in CARTITUDE-1, CARTITUDE-2 and CARTITUDE-4 trials.

ORR of cilta-cel was reported to be 95% in Ly et al. and 82% in Gregory et al., compared to 80-100% in studies based on administration in the inpatient setting. PFS at one year was 86% in Waqar et al. for outpatient administration, compared to 75-94% in the inpatient setting. OS rate at one year was 96% in Waqar et al. for outpatient administration, compared to 78-94% in the inpatient setting. Waqar et al. also reported that PFS and OS outcomes were similar across administration types.

Any grade CRS was reported to be 79% in Ly et al. (median duration 2 days, median time to onset 6 days), compared to 60%-100% in inpatient administration (median duration 2.5-9 days, median time to onset 7-9 days). Immune effector cell-associated neurotoxicity syndrome was reported to be 17% in Ly et al., compared to 2-33% in the inpatient setting.

Two studies evaluated the economic impact of cilta-cel administration in the outpatient setting. Jagannath et al. reported a cost savings of $18,922 per patient, while in the cost per responder analysis by Hansen et al., a scenario analysis with patients receiving outpatient infusion led to lower cost per complete responder and cost per month in PFS for cilta-cel (by $7,598 and $294, respectively) versus inpatient administration.

In a mixed-methods qualitative study by Hansen et al., participants agreed that cilta-cel can be safely administered in an outpatient setting, with dedicated outpatient infrastructure and close outpatient monitoring for toxicity management, due to predictable, delayed onset of potential AEs offering financial sustainability, lower resource utilization, and greater patient autonomy.

Conclusion

Upon instituting recommended processes, outpatient administration and management of cilta-cel has been shown to produce clinical outcomes comparable to traditional inpatient administration, while resulting in cost savings and improved patient quality of life. No additional safety concerns were identified with outpatient administration.

De Braganca:Janssen: Current Employment; Johnson and Johnson: Current Employment, Current holder of stock options in a privately-held company. Alegria:Janssen: Current Employment. Perciavalle:Legend Biotech: Current Employment, Current equity holder in publicly-traded company. Ranjan:Putnam, Inizio Advisory: Current Employment, Other: Putnam Inizio Advisory was contracted by Janssen to work on this project. Mothe:Putnam, Inizio Advisory: Current Employment, Other: Putnam Inizio Advisory was contracted by Janssen to work on this project. Bixby:Janssen: Current Employment, Current equity holder in publicly-traded company. Qureshi:Janssen Scientific Affairs, LLC: Current Employment, Current equity holder in publicly-traded company.