Chemotherapy with the use of next‐generation tyrosine kinase inhibitors based on measurable residual disease has the potential to avoid hematopoietic stem cell transplantation in treatment for adults with Philadelphia chromosome–positive acute lymphoblastic leukemia

Abstract Background Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) as postremission treatment is recommended for Philadelphia‐positive acute lymphoblastic leukemia (Ph+ ALL) in current guidelines. However, comparisons of later generation tyrosine kinase inhibitors (TKIs) plus chemotherapy with allo‐HSCT have yielded similar outcomes. This meta‐analysis was performed to evaluate allo‐HSCT in first complete remission (CR1) versus chemotherapy for adult Ph+ ALL in the TKI era. Methods Pooled assessment of the hematologic and molecular complete response rates was performed after 3‐month TKI treatment. Hazard ratios (HRs) were determined for disease‐free survival (DFS) and overall survival (OS) benefit with allo‐HSCT. The effect of measurable residual disease status on survival benefit was also analyzed. Results Thirty‐nine retrospective and prospective single‐arm cohort studies involving 5054 patients were included. Combined HRs indicated that in the general population, allo‐HSCT favorably influenced DFS and OS. Achieving complete molecular remission (CMR) within 3 months after starting induction was a favorable survival prognostic factor regardless of whether the patient had undergone allo‐HSCT. Among the patients with CMR, survival rates in the nontransplant subgroup were comparable with those in the transplant subgroup, with the estimated 5‐year OS of 64% versus 58% and 5‐year DFS of 58% versus 51%, respectively. The use of next‐generation TKIs results in a higher proportion of patients achieving CMR (ponatinib 82% vs. imatinib 53%), while improving survival in nontransplant patients. Conclusion Our novel findings suggest that combination chemotherapy plus TKIs leads to a comparable survival benefit as with allo‐HSCT for MRD‐negative (CMR) patients. This study provides novel evidence for allo‐HSCT indications for Ph+ ALL in CR1 in the TKI era.