This Chemotherapy-Free Regimen Appears Effective for Ph-Positive ALL

By Kerri Fitzgerald - Last Updated: December 19, 2022

A study found that simultaneous treatment with ponatinib and blinatumomab was safe and effective in patients with newly diagnosed Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). The results were presented at the 2022 American Society of Hematology Annual Meeting.

The phase II study included adults with newly diagnosed Ph-positive ALL; patients who had received one to two previous cycles of chemotherapy, with or without a BCR::ABL1 tyrosine kinase inhibitor, could also be enrolled. Those with uncontrolled cardiovascular disease or clinically significant central nervous system (CNS) comorbidities (except for CNS leukemia) were excluded.

Patients received up to five cycles of blinatumomab as a continuous infusion at standard doses; ponatinib 30 mg daily was started during cycle one and decreased to 15 mg daily once complete molecular response (CMR; primary endpoint) was achieved. After five cycles of blinatumomab, ponatinib was continued for at least five years. Patients also received 12 doses of prophylactic intrathecal chemotherapy with alternating cytarabine and methotrexate.

Between June 2018 and May 2022, 40 patients were enrolled, with a median patient age of 57 years (range, 20-83 years), and 30 patients (75%) had the p190 fusion protein. The median CD19 expression was 99.8% (range, 74.9-100%).

Among the 28 patients who were evaluable for hematologic response, 27 (96%) achieved complete remission (CR) or CR with incomplete count recovery, 26 (93%) of whom achieved CR. One patient died on day 18 from intracranial hemorrhage in the setting of cytoreductive chemotherapy administered prior to enrollment.

All hematologic responses occurred after the first treatment cycle. Among the 38 patients who were evaluable for CMR, 26 (68%) achieved CMR after the first treatment cycle, and 33 (87%) achieved CMR at any time. Molecular responses occurred rapidly, and after two weeks of therapy, 15 of 20 tested patients (75%) had achieved CMR in the peripheral blood.

Of 25 test patients, 22 (88%) also became minimal residual disease-negative by next-generation sequencing (NGS) assay with sensitivity of 1×10-6. Three of these patients had detectable low-level BCR::ABL1 transcripts by polymerase chain reaction (PCR) at the same time (range, 0.01-0.05%). The researchers did not observe any patients who were negative for BCR::ABL1 by PCR but positive by NGS.

Patients received a median of five treatment cycles (range, 1-5 cycles). Among 39 patients who received at least one complete cycle of combination treatment, one died in CR due to hypovolemic shock following cardiac catheterization, while the remaining patients are in ongoing hematologic remission. One patient went on to receive transplant at first remission due to persistently detectable BCR::ABL1 transcripts of 0.01% to 0.05%.

After a median follow-up of 15 months (range, 2-49 months), estimated two-year event-free and overall survival were both 95%. No relapses or leukemia-related deaths were observed. Among the 37 patients in ongoing remission without transplant, the median duration of response is 14 months (range, 1-44 months).

Most toxicities were grade 1/2 and consistent with the known toxicities of the two agents, according to the authors. No grade 4/5 adverse events occurred. Two patients discontinued ponatinib due to potentially related adverse events.

The researchers concluded that this chemotherapy-free regimen results in high rates CMR and MRD negativity, seemingly reducing or delaying the need for transplant in this patient population.


Short N, Kantarjian H, Jain N, et al. Ponatinib and blinatumomab for patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a subgroup analysis from a phase II study. Abstract #213. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.

Post Tags:ASH22
Editorial Board