Stalled CARS. Examining the Real-World Impact of Waiting for CART in Patients with Multiple Myeloma

Background:

Chimeric antigen receptor T-cell (CART) therapy has been commercially available in the United States for patients with multiple myeloma (MM) since 2021. Up until recently, both idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) were only approved for patients after four or more previous lines of therapy. Additionally, not all eligible patients are able to access CART therapy due to limited slots at available treatment centers. Even when slots are open, the process from referral to apheresis and cell infusion can be time consuming.

Methods:

This retrospective study was conducted at The University of Kansas Health System (TUKHS) in collaboration with the US Myeloma Innovations Research Collaborative (USMIRC). We identified patients with MM at a large academic medical center referred for CART therapy between March 2021 and December 2023. Ide-cel was approved in February 2021 and available in March 2021 at our center; while cilta-cel was approved in February 2022 and available from April 2022. Our primary intent was to analyze waiting time and outcomes. Patients were “CART recipients” if they received the infusion from time to referral until April 2024; and not “CART recipients” if they did not receive the infusion regardless of having undergone leukapheresis.

Results:

There were 179 patients with a total of 271 individual referrals for CART therapy during this period. Fifty nine patients (32.9%) had multiple referrals with a median of 1 (1-5). The average age at the time of consultation was 64 years (34-85) with 54% of patients being male. Patients had a median of 5 prior lines of therapy with 78% having previously undergone autologous stem cell transplants and 20% with prior BCMA exposure.

Only 88 patients (49.2%) proceeded to collection for autologous CART at the time of data cut off: 19 (21.6 %) received CART in 2021, 32 (36.4%) in 2022, 21 (23.9%) in 2023, and 10 (11.4 %) in 2024. Six patients (6.8%) collected for CART did not proceed with infusion; 4 due to disease progression and eventual death, and 1 each due to death from a stroke and patient choice. An additional 6 referrals (2.2%) proceeded with investigational allogeneic CART.

The most common reasons patients did not proceed to cell collection included lack of slot availability (n=37) poor performance status (n=17), patient choice (n=15) and the lack of a caregiver (n=7). Slot availability did improve over time with 25 (36.8%) and 12 (16.7%) patients in 2021 and 2022 declined due to the lack of a collection slot. Disease characteristics not meeting FDA approval criteria accounted for the majority of the reasons for referrals not proceeding with CART, with 36 patients having CART delayed due to stable disease and 38 patients identified with inadequate prior lines of therapy.

The median time to cell collection from initial consultation was 25 days (0-95 days). A total of 6 patients that proceeded with collection did not receive product due to disease progression (n=4), death (n=4), or patient preference (n=1). Of the 83 patients who proceeded with cell infusion, the median time from cell apheresis to infusion was 49 days (34-208 days) with 42 days for ide-cel (34-91) and 60 days for cilta cel (39-208). For the patients who did not proceed with collection, 12 patients (6.7%) succumbed to their disease within 90 days of their consultation for CART.

Conclusion:

While slot availability for CART has improved since initial regulatory approval, there are still eligible patients who are unable to receive this treatment due to multifactorial reasons; including lack of slot availability, poor performance status, and caregiver concerns. Emphasis must also be placed on reducing the time from initial consultation, leukapheresis, cell manufacture, and cell infusion. Given careful patient selection based on FDA eligibility criteria, insurance approval was not a barrier.

Mushtaq:Iovance Biotherapeutics: Research Funding. Atrash:Karyopharm: Research Funding; Janssen: Honoraria; Amgen: Research Funding; GSK: Research Funding. McGuirk:Allo Vir: Consultancy; Caribou bio: Consultancy; Envision: Consultancy; Autolus: Consultancy; NEKTAR therapeutics: Consultancy; CRISPR therapeutics: Consultancy; Legend biotech: Consultancy; Sana technologies: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy. Lutfi:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Ahmed:Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Mahmoudjafari:Janssen: Consultancy; Sanofi: Consultancy.