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

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.