The following is a summary of “Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial” published in the January 2023 issue of Haematology by Jabbour et al.

Patients with acute lymphoblastic leukemia with the Philadelphia chromosome (Ph-positive) may find that the combination of ponatinib and blinatumomab is a successful therapy. Researchers in this study aimed to evaluate the efficacy of this approach, which does not involve chemotherapy. Patients with newly diagnosed, relapsed, or refractory Ph-positive acute lymphoblastic leukemia or chronic myeloid leukemia in the lymphoid blast phase were included in a single-center, single-arm, phase 2 research at the University of Texas MD Anderson Cancer Center in Houston, Texas, USA. Patients were included if they met the criteria: ECOG performance status of 2 or less; total bilirubin concentration of 2.4 or less (24 mg/dL); alanine aminotransferase and aspartate aminotransferase concentration of no more than 3xULN; serum lipase and amylase concentration of no more than 3xULN. Up to five 42-day cycles of oral ponatinib 30 mg and intravenous blinatumomab 28μg over 24 h (for 28 days each cycle) were given, with subsequent ponatinib monotherapy. As central nervous system prophylaxis, patients were given a total of 12 intrathecal chemotherapeutic infusions. The primary objectives were total response in patients with relapsed or refractory illness or chronic myeloid leukemia in the lymphoid blast phase and complete molecular response in patients with newly diagnosed disease.

After enrolling 70 patients initially, the trial was expanded on March 23, 2022, to include an additional 20 participants for 90. Around 60 (83%) of the 72 patients evaluated between February 6, 2018, and May 6, 2022, were enrolled and received ponatinib and blinatumomab (40 (67%) patients with newly diagnosed Ph-positive acute lymphoblastic leukemia, 14 (23%) with relapsed or refractory Ph-positive acute lymphoblastic leukemia, and 6 (10%) with chronic myeloid leukemia in lymphoid blast phase). The mean age of the participants was 51 years, with 32 (53%) being male and 28 (47%) being female (IQR 36–68). All participants were followed for an average of 16 months (IQR 11–24). Of 38 patients evaluated for a complete molecular response, 33 (87%) were identified with newly diagnosed Ph-positive acute lymphoblastic leukemia.

12 (92%) of the 13 evaluable patients with relapsed or refractory Ph-positive acute lymphoblastic leukemia obtained an overall response. In addition, 11  of them (or 79%) showed a full molecular response. The overall response was seen in 5 (83%) of 6 individuals with chronic myeloid leukemia at the lymphoid blast phase. 

About 2 of them (33.3%) showed a full molecular response. Infection (22 patients, or 37% of the total), elevated amylase or lipase concentration (five patients, or 8% of the total), elevated alanine aminotransferase or aspartate aminotransferase concentration (four patients, or 7% of the total), pain (four patients, or 7% of the total), and hypertension (four patients, or 7% of the total) were the most common grade 3-4 adverse events. The side effect of tremors led 1 patient to stop taking blinatumomab. 3 individuals (5%) stopped using ponatinib secondary to cerebrovascular ischemia, portal vein thrombosis, and coronary artery stenosis. There were no reported deaths that could be attributed to the treatment. High rates of full molecular response were shown with the chemotherapy-free combination of ponatinib and blinatumomab in patients with newly diagnosed and relapsed or refractory Ph-positive acute lymphoblastic leukemia. The impact of chemotherapy and the requirement for allogeneic hematopoietic stem cell transplantation may be avoided in the initial response for patients with newly diagnosed Ph-positive acute lymphoblastic leukemia.

Source: thelancet.com/journals/lanhae/article/PIIS2352-3026(22)00319-2/fulltext#%20