Efficacy and safety of high-intensity versus reduced-intensity induction in Philadelphia chromosome-positive all ineligible for HSCT.

Abstract

e19031 Background: Treatment options for Philadelphia chromosome-positive (Ph+) ALL are increasing. When combined with TKIs, it is unclear if high-intensity regimens lead to a survival benefit compared to reduced-intensity regimens in patients that are not candidates for allogenic hematopoietic stem cell transplant (HSCT). In this study, we sought to examine outcomes of high-intensity and reduced-intensity induction regimens and concurrent TKI administration with respect to toxicity, response, and survival in non-transplant candidates. Methods: We retrospectively analyzed 31 patients with Ph+ B-ALL treated at our institution during January 2015 to January 2021 that were not candidates for HSCT. Baseline patient demographics were obtained, including age, performance status at diagnosis, cytogenetic and molecular profiling through NGS, doses of induction, toxicity, response, MRD analysis, and survival. The event for calculating the overall survival (OS) was the date of death and patients were otherwise censored at the date of last contact. Results: We divided the cohort of 31 patients into two sub-cohorts: a high-intensity cohort of 22 patients treated with TKIs and hyperCVAD, CALGB 10403, or ECOG 1910 and a low-intensity cohort of 9 patients treated with TKI + steroids + vincristine, TKI + steroids, or TKI alone. There was expectedly a significant difference in age between the two groups (p = .002) with more advanced age in the reduced-intensity cohort, though no difference in sex (p≥.999), ECOG score at diagnosis (p = .886), or Charlson Comorbidity Index score (p = .180). Grade 3 or higher toxicity was approaching statistical significance with more toxicity in the higher-intensity group (p = .075). With fewer deaths during induction, achievement of CR or CRi was higher in the reduced-intensity cohort (100% versus 73.7%), though was not significantly different between the groups (p = .288) and the median OS was not reached in either cohort (p = .935) after a median follow-up time of 3.29 years. Conclusions: Acknowledging the limits of a small sample size and retrospective nature of the study, there was no observed difference in survival between high-intensity and reduced-intensity induction with TKIs for patients ineligible for HSCT. Reduced-intensity inductions were associated with a trend toward less severe toxicity. These findings are suggestive that reduced-intensity induction with TKIs in Ph+ ALL may represent a reasonable option for those ineligible for HSCT. Prospective randomized controlled trials in this population are warranted.