Geographic/Financial Barriers to CAR T Therapy Exist in Hematologic Cancers

“[The data support] investigating an individualized monitoring period for stable patients to decrease barriers, although caution is advised due to ongoing risks of late adverse events," according to the study authors.

A majority of patients with multiple myeloma or non-Hodgkin lymphoma lived more than 30 minutes from a cancer center that administers CAR-T cell therapy, highlighting the financial and geographic barriers that exist with this therapeutic approach, as well as a need to create specific monitoring periods for adverse effects (AEs) for these patients.

Results of a retrospective analysis showed that more than 60% of 256 patients in the analysis lived beyond a half-hour from a CAR T-cell administering center. Moreover, there was a low incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the 2 weeks following CAR T infusion.

When stratified by product, the median onset to CRS was 2 days with axicabtagene ciloleucel (axi-cel, Yescarta; n = 91), 2 days with tisagenlecleucel (tisa-cel, Kymriah; n = 31), 2.5 days with lisocabtagene maraleucel (liso-cel, Breyanzi; n = 18), 2.5 days with brexucabtagene autoleucel (brexu-cel, Tecartus; n = 10), 7 days with ciltacabtagene autoleucel (cilta-cel, Carvykti; n = 14), and 1 day with idecabtagene vicleucel (Abecma; n = 90). The median number of days until ICANS onset was 6, 3, 8, 6, 26, and 2, respectively. When broken down further, the onset of CRS and ICANS on days 0 to 6 was highest with axi-cel and ide-cel.

“[The data support] investigating an individualized monitoring period for stable patients to decrease barriers, although caution is advised due to ongoing risks of late adverse events,” lead study author William Wesson, MD, a medical student at University of Kansas School of Medicine, and coinvestigators noted in the publication.

As part of the FDA’s mandated Risk Evaluation and Mitigation Strategy (REMS) for both BCMA and CD19-directed CAR T-cell therapy, patients are required to reside near the treatment center for 4 weeks for CRS/ICANS mitigation, with most centers giving patients a drive time cutoff of 30 minutes.

Potential challenges relating to finances and treatment access due to the monitoring period have been previously noted, the authors wrote. Therefore, investigators sought to determine the optimal duration of monitoring for CRS and ICANS. This included defining the timing of CRS and ICANS incidence and their duration following CD19- and BCMA-directed CAR T-cell therapies, as well as identifying cytopenia incidence after CAR T-cell therapy and use of supportive care.

In the retrospective analysis, investigators analyzed 256 adult patients with lymphoma or multiple myeloma across 4 medical centers in the United States. Patients were treated with either axi-cel, tisa-cel, liso-cel, brexu-cel, cilta-cel, or ide-cel.

Patients’ baseline characteristics were compared based on whether they experienced onset of CRS/ICANS within 7 days of treatment (n = 216) or after 7 days (n = 38). The median age at leukapheresis was 63 years (IQR, 57-70) and 67 years (IQR, 60-70; P = .316), and 45% and 55% of patients, respectively, were 65 years and older (P = .291). A total of 53% and 54% of patients in each group were men (P = .862), and 87% and 91% had an ECOG performance status of 0 or 1 (P = .585). Additionally, 12% and 16% of patients across the 2 cohorts were Black (P = .228).

Of those experiencing CRS/ICANS within 7 days, 56% had non-Hodgkin lymphoma compared with 79% in the CRS/ICANS at day 7 and beyond group. Forty-four percent and 21%, respectively, had relapsed/refractory multiple myeloma. In the shorter onset cohort, 37% of patients had a drive that was 30 minutes or less from their treatment center, while 63% had a drive longer than a half-hour. In the CRS/ICANS onset at day 7 or later group, these rates were similar at 34% and 66%, respectively.

Insurance status was evenly split between the 2 groups with Medicare/Medicaid and commercial insurance.

When evaluated following treatment infusion, CRS incidence occurred in 75% and 92% of those before day 7 and after day 7, respectively (P = .020); the median days to onset was 1 (IQR, 1-3), and 5 (IQR, 2-8), respectively (P <.001), and the median days to resolution was 5 (IQR, 2-6), and 7 (IQR, 4-10), respectively (P = .002). One patient in each group had onset of CRS beyond day 14 (P = .277).

ICANS incidence occurred in 28% of patients before day 7 and in 82% of those after day 7 (P <.001). The median days to onset was 3 (IQR, 2-5) and 9 (IQR, 7-12), respectively (P <.001), and the median days to resolution was 7 (IQR, 3-12) and 11 (IQR, 4-18), respectively (P = .064). One patient in each group had ICANS onset beyond day 14 (P = .277).

Tocilizumab (Actemra) administration was similar between the 2 groups with at least 1 dose given in 63% of patients experiencing CRS/ICANS within 7 days and 66% of those in the beyond day 7 group (P = .856). Additionally, at least 1 dose of steroids was given in 34% of patients with CRS/ICANS before day 7 and in 61% of those after day 7 (P = .003).

Investigators also evaluated the incidence of cytopenias in both groups. Grade 3 or higher anemia at day 14 in those who had CRS/ICANS onset before day 7 occurred in 10% compared with 13% of those who had CRS/ICANS onset after day 7 (P = .572). There were additional comparisons of grade 3 or higher thrombocytopenia at day 14 (28% vs 32%; P = .697), grade 3 or higher neutropenia at day 14 (45% vs 26%; P = .034), grade 3 or higher anemia at day 30 (18% vs 16%; P = 1.000), grade 3 or higher thrombocytopenia at day 30 (40% vs 38%; P = .857), and grade 3 or higher neutropenia at day 30 (35 vs 35%; P = 1.000).

As part of supportive care, packed red blood cell transfusions administered between days 15 and 30 were given to 20% of patients who had CRS/ICANS onset on before day 7 and to 26% for those who had it after day 7 (P = .398). Rates of platelet transfusions given between day 15 and 30 were 22% and 21%, respectively (P = 1.00) and the rates of granulocyte-colony stimulating factor given between days 15 and 30 was 38% and 50% (P = .156), respectively.

Investigators presented these findings during the 2024 Transplantation and Cellular Therapy Meetings.

Reference

Wesson W, Dima D, Davis J, et al. A multicenter experience: duration of mandatory CRS and ICANS monitoring for myeloma and lymphoma CAR T recipients. Transplant Cell Ther. 2024;30(2):S207-S208. doi:10.1016/j.jtct.2023.12.269