Efficacy and safety of asparagine-depleting regimens versus HyperCVAD in adults with Philadelphia chromosome-positive B-ALL: A retrospective analysis.
Authors: Alnimer Yanal Mufeed , Bouligny Ian Michael , Zacholski Kyle , Venn Chad Michael , Tran Valerie , Ho Thuy , Maher Keri Renee 
Published: June 2022

e19040

Background: The optimal treatment of adults with Philadelphia chromosome-positive (Ph+) B-ALL remains unclear. Use of pediatric-inspired regimens (PIRs) featuring asparagine depletion is associated with high responses, although at the expense of increased toxicity. Moreover, PIRs have not directly been compared with regimens that do not contain asparagine depletion (e.g., hyperCVAD). Thus, the aim of this study was to compare toxicity and efficacy of asparagine-depleting PIRs versus hyperCVAD in a matched retrospective population of adults with Ph+ B-ALL. Methods: We identified 30 patients ≥21 years with Ph+ B-ALL treated at our institution during January 2015 to January 2021. In the upfront setting, 9 were treated with PIRs. A comorbidity-matched cohort of 21 patients ≤60 years treated with hyperCVAD was selected as a comparison. Baseline patient demographics were obtained, including age, ECOG score, and comorbidities at diagnosis, cytogenetic and molecular profiling, toxicity, response, MRD analysis, survival, and receipt of hematopoietic stem cell transplant (HSCT). Results: In the PIR cohort, the median age was 37, 55.6% were male, median ECOG score was 1, and median Charlson Comorbidity Index (CCI) score was 2. CALGB 10403 was used in 88.9% of patients and 11.1% received ECOG 1910; all patients received a TKI. All patients experienced at least one grade ≥3 toxicity, and there was a total of 31 unique grade ≥3 toxicities and no deaths during induction. The composite response rate (CRR) was 77.8% and 50.0% of responders were MRD-negative. In the cohort treated with hyperCVAD and TKIs, there was no difference in age (p = .125), sex (p = .694), ECOG (p = .538), or CCI score (p = .851). There were 18 unique grade ≥3 or higher toxicities, which was significantly fewer than the PIR cohort (p = .021), though the rate of neutropenic fever was higher in hyperCVAD (p = 0.016). There were no deaths during induction and the CRR was 94.4% – not significantly different from the PIR cohort (p = .250) with 60.0% MRD-negative. HSCT was performed for 61.9% of patients in the hyperCVAD group versus 44.4% in the PIR cohort (p = .443). Despite this, the median survival was not reached in either cohort after a median follow-up time of 3.3 years. The cumulative probability of survival at 5.4 years was 100% in the PIR cohort and 76.9% in the hyperCVAD cohort. Conclusions: Our findings suggest that PIRs feature significantly increased grade ≥3 toxicity with evidence of a higher probability of survival at 5.4 years compared to hyperCVAD, although the median survival was not reached and there was no difference between the two arms at the time of follow-up. Patients must be carefully selected for receipt of PIRs given the expected increased burden of toxicity with these regimens. Although long-term survival appears to favor PIRs, larger studies and longer follow-up are needed to confirm these findings.