Adoption of Approved CAR-T Therapies Among US Community Hematologists/ Oncologists

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor T-cell (CAR-T) therapies approved in the United States (US) for the treatment of relapsed or refractory large B-cell lymphoma (R/R LBCL). Almost half of all patients with cancer are treated in community-based oncology practices in the US. Understanding the adoption of novel therapies by community hematologists/oncologists (cH/O) is critical to assessing their future utilization and impact on clinical outcomes. We sought to study the temporal trends of CAR-T utilization over a year among cH/O and their perceptions regarding the barriers to adoption of CAR-T therapies in R/R LBCL in a descriptive study using survey-based methodology.

Methods: Live meetings held in February 2019 (cohort A) and Winter 2020 (November 2019-February 2020, cohort B) convened cH/O of diverse US regions and practice types to better understand perceptions around CAR-T, its utilization in R/R LBCL, and referral patterns. Participants were compensated for participation and submitted responses via web-based pre-meeting surveys and live audience response system. All responses are summarized using descriptive statistics. A subset analysis was performed for the cH/O who were surveyed in both cohort A and cohort B.

Results: A total of 59 and 168 cH/O participated in this research study in cohorts A and B, respectively: 61% and 70% of participants identified their primary specialty as hematology/oncology; in a private community practice (50% and 56%), or community practice owned by a hospital or academic center (44% and 24%, p=.003). Both groups reported seeing an average of >20 patients per day.

The proportion of cH/O who indicated that they had referred at least one patient for CAR-T therapy for R/R LBCL in the preceding 6 months was 54% and 93% (p<.00001) in cohorts A and B, respectively. The median number of patients referred for CAR-T therapy in the preceding 6 months in cohorts A and B was 1 and 2, respectively. Of those who had referred patients, 32% and 29% indicated that none of the patients referred had yet received the product infusion. Among the 30 physicians who participated at both time points, the percentage of those who had referred a patient for CAR-T in the preceding 6 months was 57% and 41% (p=.25), and the rates of non-receipt of product infusion for all referred patients among these 30 cH/O was 29% and 36% (p=.09) for the 2019 and 2020 timepoints, respectively.

The major barriers to utilization of CAR-T therapy identified in cohorts A and B, respectively, included: the cost of the therapy (46% and 64%, p=.01), high toxicity (24% and 38%, p=.07) and lack of long-term survival data (19% and 24%, p=.66). The logistics of CAR-T process were identified by over half (52%) of cH/O as a barrier to utilization in cohort A. This issue of logistics was explored further in cohort B with barriers to intake of patients being attributable to either the payer or the CAR-T center. The payer-specific challenges included slow approval process by payers (27%) and high rates of denials by payers (15%). The challenges specific to the CAR-T center included a slow intake process (23%) and a lack of a CAR-T center in geographic vicinity (13%). Other challenges reported by the participants included deterioration of the patient prior to CAR-T administration (64%) and the lack of communication from the CAR-T center during the process, including lack of instructions to the primary oncologist (14%) and the patient (6%).

Conclusions: Overall, the probability of referral for CAR-T therapies in R/R LBCL among cH/O increased over the study period. The proportion of patients unable to receive CAR-T product has remained relatively constant at almost one-third of patients referred. Among physicians who were polled at two timepoints, there does not seem to be increased adoption of CAR-T therapy, though this may arise from the relative rarity of the appropriate patients. High cost and toxicity continue to be potential deterrents to CAR-T consideration and appear to be increasing in significance. These findings can assist manufacturers, payers, and CAR-T centers to focus on modifiable process improvements in patient referral, payer-authorization, and improved intake to facilitate timely access to a potentially curative therapy for patients with R/R LBCL.