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High Rates of Remission, MRD Negativity with Ponatinib Plus Blinatumomab in Ph+ ALL

leukemia cell death

By  Cecilia Brown - January 10, 2023

A chemotherapy-free regimen with simultaneous ponatinib and blinatumomab was “safe and effective” in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), according to results from a phase II study.


Nicholas Short, MD, of the MD Anderson Cancer Center, and colleagues conducted the study and presented its results at the 2022 American Society of Hematology Annual Meeting and Exposition.

The study included 40 adults with newly diagnosed Ph+ ALL. The median patient age was 57 years. Patients who previously received one to two cycles of chemotherapy, with or without a BCR-ABL1 tyrosine kinase inhibitor, were eligible for enrollment.

The patients received up to five cycles of blinatumomab at standard doses as a continuous infusion and began receiving ponatinib 30 mg daily during the first cycle, decreasing to 15 mg daily when patients achieved a complete molecular response. Patients continued to receive ponatinib for at least five years after completing the five cycles of blinatumomab. Patients received a median of five cycles of blinatumomab.

Of the 40 patients enrolled, 12 patients were in complete remission at enrollment and 28 patients were evaluable for a hematologic response, with 93% of those patients achieving a complete remission. All hematologic responses occurred after one cycle. Most (68%) of the 38 patients who were evaluable for molecular complete remission achieved a molecular complete remission after the first cycle, with 87% achieving a complete molecular remission at any time.

“Molecular responses occurred rapidly, and after only two weeks of therapy, 15 of 20 tested [patients] (75%) had achieved [complete molecular remission] in the peripheral blood,” Dr. Short and colleagues wrote.

Nearly all (88%) of the 25 patients who were tested for minimal residual disease (MRD) with next-generation sequencing were MRD negative at 1 × 10−6. However, three of the patients who were MRD negative had low levels of BCRABL1 detectable by polymerase chain reaction (PCR). None of the patients who were negative for BCRABL1 by PCR testing were positive when evaluated with next-generation sequencing.

The estimated two-year event-free survival rate at a median follow-up of 15 months was 95%, as was the estimated two-year overall survival rate. The median duration of response was 14 months in the 39 patients who were in ongoing remission without hematopoietic stem cell transplantation (HSCT). Only one patient underwent HSCT in their first complete remission.

No grade 4-5 related adverse events, relapses, nor leukemia-related deaths occurred. Two patients discontinued ponatinib “due to possibly related adverse events,” according to the study’s authors.

“The treatment was well-tolerated, and most toxicities were grade 1-2 and consistent with the known toxicities of the two agents,” Dr. Short and colleagues wrote.

Among the 39 patients who received at least one complete cycle of ponatinib-blinatumomab, one of the patients died during complete remission due to hypovolemic shock following cardiac catheterization, but the other 38 patients are in ongoing hematologic remission.

“Simultaneous ponatinib and blinatumomab is safe and effective in [patients] with newly diagnosed Ph+ ALL,” Dr. Short and colleagues concluded. “This chemotherapy-free regimen results in high rates of [complete molecular remission] and [next-generation sequencing] MRD negativity. Encouraging survival has been observed without the need for [HSCT].”


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.

Original Source: High Rates of Remission, MRD Negativity with Ponatinib Plus Blinatumomab in Ph+ ALL | Blood Cancers Today

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