Treatment‐free remission in nontransplanted patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia

Abstract Background The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have significantly improved the outcomes of patients with Philadelphia chromosome (Ph)‐positive acute lymphoblastic leukemia (ALL). However, the optimal duration of TKI therapy in patients who achieve a complete molecular response (CMR; undetectable BCR::ABL1 transcripts) and who do not undergo allogeneic stem cell transplantation (allo‐SCT) remains undefined. Methods The authors conducted a retrospective analysis of patients with Ph‐positive ALL in first complete remission who achieved a CMR and discontinued TKI therapy, most commonly due to treatment‐related side effects. Results In total, 14 patients were identified. The regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high‐dose methotrexate and cytarabine was the primary backbone chemotherapy and was received by 12 patients (86%) combined with either imatinib (14%), dasatinib (43%), or ponatinib (29%) during induction. Two patients received blinatumomab and ponatinib. The median duration of TKI therapy was 60 months. The median CMR duration before TKI discontinuation was 46.1 months (range, 2.7–121.3 months). After a median follow‐up of 42.5 months from TKI discontinuation, three patients (21%) experienced relapse (two molecular, one morphologic), whereas 11 patients (79%) maintained treatment‐free remission. The median time to relapse was 6.4 months (range, 4–16 months), and two of three relapsed patients regained CMR after resuming TKI therapy. Importantly, none of the six patients with a CMR duration >48 months before TKI discontinuation relapsed. Conclusions The current findings suggest that TKI discontinuation may be safe for highly selected patients with Ph‐positive ALL in first complete remission who maintain CMR for at least 48 months. Larger studies are needed to confirm these findings.