Practice preferences for consolidative HSCT following tisagenlecleucel in children and young adults with B-ALL.

BACKGROUND: Tisagenlecleucel achieves excellent complete remission rates in children and young adults with relapsed or refractory B-acute lymphoblastic leukemia (B-ALL), but approximately 50% maintain long-term remissions. Consolidative hematopoietic stem cell transplant (cHSCT) is a potential strategy to reduce relapse risk but carries substantial short- and long-term toxicities. Additionally, several strategies for management of B-cell recovery (BCR) and next-generation sequencing (NGS) positivity post-tisagenlecleucel exist without an accepted standard. We hypothesized that practice preferences surrounding cHSCT as well as management of BCR and NGS positivity varies across tisagenlecleucel-prescribing physicians and sought to characterize current practice preferences.

METHODS: A survey focused on preferences regarding the use of cHSCT, management of BCR, and NGS positivity was distributed to physicians that prescribe tisagenlecleucel for children and young adults with B-ALL. Responses were collected from August 2022 to April 2023.

RESULTS: Fifty-nine unique responses were collected across 43 institutions. All respondents prescribed tisagenlecleucel for children and young adults. The clinical focus of respondents was HSCT in 71% followed by leukemia/lymphoma in 24%. In HSCT-naïve patients receiving tisagenlecleucel, 57% of respondents indicated they made individualized decision for cHSCT based on patient factors, while 22% indicated they would avoid and 21% indicated they would pursue cHSCT where feasible. Select factors influenced >50% of respondents towards recommending cHSCT (either increased likelihood or would always recommend) including pre-infusion disease burden >25%, primary refractory B-ALL, M3 bone marrow following re-induction for relapse, KMT2A-rearranged B-ALL, history of blinatumomab non-response, and HSCT naïve status. Most respondents indicated they would pursue HSCT for HSCT-naïve, total body irradiation candidates with BCR before 6 months post-tisagenlecleucel or with NGS positivity at 1 or 3 months post-tisagenlecleucel, although there was variability about whether to proceed to HSCT directly or give intervening therapy prior to HSCT. The proportion of respondents recommending HSCT for BCR or NGS positivity decreased in those with a history of HSCT, non-TBI-candidates, or trisomy 21.

CONCLUSIONS: The results of this survey indicate there exists significant practice variability regarding the use of cHSCT as well as interventions for post-tisagenlecleucel BCR or NGS positivity. These results highlight areas for which ongoing clinical trials could inform more standardized practice.