Impact of TKI combination therapy and MRD negativity on outcomes in Philadelphia chromosome-positive ALL: A retrospective, single-center experience.

Abstract

e19052 Background: Presence of the Philadelphia chromosome (Ph+) in newly diagnosed B-cell acute lymphoblastic leukemia (ALL) conveys high-risk disease and a poor prognosis. Hematopoietic stem cell transplant (HSCT) following induction and achievement of remission remains the standard of care. In the era of TKIs targeting BCR-ABL1 in addition to newer combination strategies, the impact of HSCT in the first complete remission (CR) remains unclear, particularly in the context of measurable residual disease (MRD) negativity. We present the outcomes of Ph+ B-ALL patients with and without HSCT, stratified with respect to MRD negativity. Methods: We identified 32 patients with Ph+ B-cell ALL from January 2015 to January 2021 at our institution who were treated with TKIs and received HSCT with evaluable MRD prior to transplant. Baseline patient demographics were obtained, including labs, performance status at diagnosis, comorbidities, molecular profiling by NGS, doses of induction, toxicities, response, MRD analysis by PCR, HCT-CI scores, and HSCT outcomes. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: Of the 25 patients who underwent HSCT, the median age was 46 years and 48.0% were male. TKIs in combination with high-intensity regimens were given in 88.0% of patients at induction. There were no deaths within 60 days following induction. Twenty (80.0%) patients achieved CR or CRi, and of those, 56% were MRD-negative by the time of HSCT. At a median follow-up time of 4.74 years, the OS of patients that achieved CR following induction and HSCT was not reached, and there were no significant differences between the two groups (p = .1326). We then compared the 14 MRD-negative patients undergoing HSCT to 7 MRD-negative patients who did not undergo transplant aged ≤65 years with ECOG ≤2. There was no difference in age (p = .5353), ECOG score (p = .6364), or Charlson Comorbidity Index score (p = .7018) between the two groups. The median OS in the MRD-negative HSCT group was not reached and the median OS in the MRD-negative non-HSCT was 5.45 years (p = .0210). Conclusions: In the era of combination chemotherapy with TKIs, MRD positivity at the time of allogenic HSCT does not appear to impact survival at 5 years in this small retrospective cohort. Post-transplant TKI maintenance may abrogate MRD implications at the time of HSCT. Our findings demonstrate that Ph+ ALL patients benefit from HSCT when candidates, regardless of MRD status, as those undergoing HSCT demonstrated a statistically superior survival. HSCT appears to remain the standard of care despite newer combination strategies and MRD-driven treatment.