Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of chemorefractory large B-cell lymphoma (LBCL). However, despite the robust response rates and potential for cure among patients otherwise facing dismal outcomes, there are barriers to this lifesaving treatment. The current U.S. Food and Drug Administration (FDA)-approved CAR T products require referral to a certified treatment center, insurance approval, and leukapheresis, with at least half of all patients needing to undergo bridging therapy while awaiting product manufacturing.
Those patients who become eligible for CAR T-cell therapy must be monitored for at least four weeks near the treatment center and require a caregiver to be with them following lymphocyte-depleting chemotherapy and cell infusion. They also must refrain from operating heavy equipment for eight weeks. These requirements lead to geographic and socioeconomic obstacles that affect the uptake of CAR T-cell therapy. A Medicare fee-for-service claims database analysis revealed that only 13 to 22% of patients aged 65 years or older otherwise eligible in third line with diffuse LBCL received CAR T-cell therapy.1 Do minority patients face similar obstacles?
Guido Ghilardi, MD, and colleagues examined whether minority patients with LBCL had equal access and similar outcomes compared to non-minority patients treated with commercial CAR T-cell therapy at two different institutions — Penn Medicine’s Abramson Cancer Center (ACC) in Philadelphia and the OHSU Knight Cancer Institute (KCI) in Portland, Oregon. Patients diagnosed with lymphoma in the catchment areas of each institution between January 2015 and December 2019 were included (ACC, n=8,956; KCI, n=4,568). The ACC catchment area had an above-average prevalence of minority patients (17.9%), whereas the KCI catchment area had a comparatively lower prevalence of such patients (4.2%) but included more rural areas. Among those with LBCL, 15.8% from ACC and 6.6% from KCI self-reported as minorities, with most living inside the institutions’ catchment areas. Though small in number, both centers had a similar percentage of total minority patients with LBCL who were receiving CAR T-cell therapy (~4-6%).
The authors analyzed baseline characteristics and outcomes among minority patients with LBCL who received CAR T-cell therapy compared with a non-minority cohort. These characteristics were comparable except for age at CAR T-cell infusion, with the median age of minority patients (50) lower than that of non-minority patients (62). Among minority patients, 67% experienced cytokine release syndrome (CRS) of any grade, with 0% experiencing severe cases of CRS, compared with 63% and 9.7%, respectively, of non-minority patients. Rates of immune effector cell–associated neurotoxicity syndrome (ICANS) among minority patients were 13% for any grade and 6.7% for severe cases, compared with 22% and 10.6%, respectively, among non-minority patients. Three-month complete response rates were 66.7% in minority patients versus 42% in non-minority patients. Median progression-free survival was 3.7 months for minority patients, with a median overall survival rate of 17.4 months, compared with 3.2 months and 26.2 months, respectively, for non-minority patients.
The authors concluded that the percentage of minority patients with LBCL receiving treatment within the two institutions was similar to the demographics of their respective catchment areas. However, a comparatively smaller proportion of minority patients (n=15) received CAR T-cell therapy for LBCL at these institutions (precluding the drawing of any conclusions about whether these patients had similar outcomes), although outcomes were comparable to those previously published for commercial CAR T-cell therapy.2,3
In Brief
What should we take away from this analysis? While the prevalence of LBCL in minority patients is low, every effort should be made to ensure that tertiary center patient demographics reflect their catchment areas. Both of the geographically distinct tertiary centers involved in the study have done a good job of this, which will improve access for patients living within the catchment areas of these centers. It is not clear why the percentage of minority patients undergoing CAR T-cell therapy at these centers is lower than that of minority patients potentially eligible for CAR T-cell therapy. The authors caution that very small numbers can lead to overinterpretation. However, inequitable access at these tertiary centers to one of the most promising immunotherapy developments in recent years is alarming. Future studies should explore factors that may be contributing to this inequity, including provider bias, socioeconomic barriers, patient preference, etc. Patient navigators may be employed to help address these disparities. Further, a cancer center in Portland may not be ideally representative of a rural setting and capture the challenges faced by many Americans in underserved areas; as such, it is critical to work toward increasing the number of centers providing CAR T-cell therapy across the country.
Competing Interests
Dr. Nastoupil has received honorarium and research support from BMS, Genentech, Kite (a Gilead company), Janssen, Novartis, and Takeda.
