SOHO State of the Art Updates and Next Questions | Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Can...

The incorporation of ponatinib into the frontline regimens of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) deepened the molecular responses and improved outcomes. Patients with Ph-positive ALL who achieve a complete molecular response (CMR, undetectable BCR::ABL1 transcripts by RT-PCR) by 3 months of therapy have a better survival compared to those with persistent disease. Studies showed that the next-generation sequencing (NGS) assay, with a sensitivity up to 1 × 10^-6, is more sensitive than RT-PCR for the detection of measurable residual disease (MRD) in Ph-positive ALL and therefore carries a better prognostic value. Patients who achieve a 3-month CMR and undetectable MRD by NGS have excellent outcomes and may not need consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. However, omitting HSCT in certain patients with high-risk disease features, such as IKZF1^plus, remains to be determined. Outcomes were significantly improved with the combination of blinatumomab and ponatinib. This chemotherapy-free regimen resulted in a CMR rate of 80% by RT-PCR and 99% by NGS, with a 3-year overall survival rate of 89%. Only 2 of 76 patients (3%) underwent HSCT in this study. Combinations of newer TKIs (such as asciminib or olverembatinib) with blinatumomab (intravenous, subcutaneous) might further improve outcomes and are being explored. Achieving durable NGS MRD negativity can identify patients at low risk of relapse who might be candidates for treatment discontinuation. In this review, we discuss the current progress in the management of Ph-positive ALL, particularly the role of chemotherapy-free regimens in mitigating the need for HSCT.