CAR-T Prescriber Preferences in Adolescents and Young Adults with B-ALL

Introduction: Since October 2021, there have been two Food and Drug Administration (FDA) approved CD19 CAR-T products (tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel)) for adolescents and young adults (AYA) aged 18 to 25 with B-cell acute lymphoblastic leukemia (B-ALL). Only a small number of AYAs were treated on both registration studies. Comparison across these single arm studies is not possible with differences in demographics and clinical management. We aim to understand prescriber preferences and rationale when deciding between products in the AYA population with B-ALL and inform future clinical investigations.

Methods: We conducted a 21-question electronic survey of CAR-T prescribers through the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC). (Note: PTCTC did not formally approve this work but assisted with survey conduct.) The survey consisted of questions about practice demographics and logistics, prescriber opinion and preferences regarding the two FDA approved CAR-T products based on literature data.

Results: There was a total of 13 completed surveys from 10 centers at the time of analysis. Most respondents primarily treat patients with hematological malignancies who are 18 years of age or younger (85%). The median FDA approved CAR-T volume among the centers were 1-5 and ranged from 0 to >20. Close to half of respondents (46%) reported their institution requiring committee discussion and approval for all CAR-T cases. Ninety-two percent prescribed tisa-cel for any indication; 23% prescribed brexu-cel for any indication. Within the past year, over half of the respondents treated at least 16 patients with B-ALL (62%) and prescribed at least one CAR-T product. Approximately 31% of the respondents discuss both CAR-T products as treatment options for AYA with B-ALL, and respondents from two centers reported that their center is only certified to prescribe tisa-cel. Since October 2021, 69% of respondents had prescribed tisa-cel for B-ALL while only 15% had prescribed brexu-cel for B-ALL. Regarding current practice, close to half (46%) reported general consensus among their institutional practice is to prescribe tisa-cel for AYA with B-ALL. No one planned to routinely prescribe brexu-cel for AYA with B-ALL, although 31% report planning to consider either CAR-T product on a case-by-case basis. The remaining 23% has no general plan: 15% not having discussed both CAR-T products as an option and 8% is unsure. When asked the clinical data for deciding tisa-cel vs brexu-cel for AYA with B-ALL, some respondents reported more data and experience with tisa-cel, including longer follow-up and better persistence with 4-1BB costimulatory domain. For patients who need CAR-T treatment more urgently, some would consider brexu-cel for the shorter vein to vein time.

The respondents were then presented with hypothetical clinical scenarios using published data without revealing the product name and asked to select CAR-T product A (tisa-cel), B (brexu-cel) or if both would be reasonable. When presented with the CR/CRi rate and the 4-1BB vs CD28 co-stimulatory CAR constructs in a blinded fashion, the percent of respondents willing to consider both products as reasonable options were comparable as that reported in practice (close to 31%, with the remaining favoring tisa-cel). However, when presented with reported OS data from both products in blinded fashion, close to 69% of the respondents selected that both products are reasonable options. When presented with product manufacturing turnaround time, 42% of respondents preferred brexu-cel while the remaining 58% respondents felt both products were reasonable.

Conclusions: AYA with B-ALL requiring CAR-T therapy are eligible for both tisa-cel and brexu-cel and there exists clinical equipoise as to which product is best for different clinical scenarios given the lack of head-to-head comparison. Most CAR-T prescribers at the time of this survey favored tisa-cel given its availability and familiarity as well as its 4-1BB costimulatory domain. However, some prescribers may favor brexu-cel if there was rapid clinical decline requiring expedited turnaround time. Some changes in product preference when clinical data was presented in a blinded manner were seen, suggesting providers' willingness and feasibility to design a pragmatic study comparing tisa-cel and brexu-cel in real world practice in the AYA population.

Kitko:Horizon Therapeutics: Consultancy. Lin:Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Merck: Research Funding; Juno: Consultancy; Gamida Cell: Consultancy; Celgene: Consultancy, Research Funding; Legend: Consultancy; Sorrento: Consultancy; Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.