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A phase II trial of a chemotherapy-free combination of ponatinib and blinatumomab in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

2022; Lippincott Williams & Wilkins; Volume: 40; Issue: 16_suppl Linguagem: Inglês

10.1200/jco.2022.40.16_suppl.7009

1527-7755

Nicholas J. Short, Hagop M. Kantarjian, Marina Konopleva, Guillermo Montalban‐Bravo, Farhad Ravandi, Nitin Jain, Tapan M. Kadia, Yesid Alvarado Valero, Kelly S. Chien, Naval Daver, Walid Macaron, Koji Sasaki, Jennifer Thankachan, Ricardo Delumpa, Ejiroghene Mayor, Wuliamatu Deen, Christopher Loiselle, Monica Kwari, Rebecca Garris, Elias Jabbour,

Chronic Lymphocytic Leukemia Research

7009 Background: Ponatinib and blinatumomab are highly active in Ph+ ALL. A chemotherapy-free combination of these agents may lead to durable remissions and reduce the need for stem cell transplant (SCT) in first remission. Methods: In this phase II study, adults with newly diagnosed (ND) Ph+ ALL, relapsed/refractory (R/R) Ph+ ALL, or CML in lymphoid blast phase (CML-LBP) received up to 5 cycles of blinatumomab. Ponatinib 30mg daily was given during cycle 1 and decreased to 15mg daily once a complete molecular response (CMR) was achieved. After completion of blinatumomab, ponatinib was continued for at least 5 years. All patients (pts) received 12 doses of prophylactic IT chemotherapy. Results: Between 2/2018 and 1/2022, 55 pts were treated (35 ND, 14 R/R and 6 CML-LBP). Baseline characteristics and responses are shown in Table. Among 23 pts with ND Ph+ ALL evaluable for response, 22 (96%) achieved CR/CRi; 1 pt had early death due to myelosuppression from prior chemotherapy. Among 13 evaluable pts with R/R Ph+ ALL, 12 (92%) achieved CR/CRi. The CMR rates for the ND, R/R and CML-LBP cohorts were 64%, 71%, and 17% after cycle 1 and were 85%, 79%, and 33% overall, respectively. In the ND cohort, 4/17 evaluable pts (24%) achieved CMR in the peripheral blood within 1 week, and 9/15 (60%) within 2 weeks. The median follow-up is 11 months (range, 1-46+ months). Among the 35 pts in the ND cohort, 33 pts (94%) are alive and in continuous remission. Only 1 pt in the ND underwent SCT in first remission (due to persistent MRD positivity), and no relapses have been observed. The 2-year EFS and OS rates in the ND cohort are 93%. Among the 13 responding pts in the R/R cohort, 6 (46%) underwent SCT. The 2-year EFS and OS rates for the R/R cohort are 42% and 61%, and for the CML-LBP cohort are 33% and 60%, respectively. Most side effects were grade 1-2 and were consistent with the known toxicity profile of the two agents individually. Two pts discontinued ponatinib due to toxicity (1 due to stroke and 1 due to DVT). One pt discontinued blinatumomab due to recurrent neurotoxicity. Conclusions: The chemotherapy-free combination of ponatinib and blinatumomab was safe and effective in Ph+ ALL and CML-LBP. Longer follow-up continues to demonstrate durable remissions, particularly in ND Ph+ ALL, even without SCT in first remission. Clinical trial information: NCT03263572. [Table: see text]