Phase II study of combination of hyperCVAD with ponatinib in frontline therapy of patients (pts) with Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL).

Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
General Poster Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 7064)
Susan Mary O'Brien, Elias Jabbour, Deborah A. Thomas, Farhad Ravandi, Jorge E. Cortes, Naveen Pemmaraju, Tapan M. Kadia, Rebecca Garris, Vicky Jeanis, Guillermo Garcia-Manero, Gautam Borthakur, William G. Wierda, Hagop M. Kantarjian; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; MD Anderson Cancer Center, Houston, TX

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Abstract Disclosures


Background: Combination of chemotherapy (CTX) with TKI is effective in the treatment of Ph+ ALL. Ponatinib is a more potent BCR-ABL inhibitor. The combination of CTX + ponatinib may be associated with better outcome. Methods: Pts with newly diagnosed Ph+ ALL received 8 cycles of hyperCVAD every 21 days. Ponatinib was given at 45 mg po daily for the first 14 days of cycle 1 then continuously for the subsequent cycles. Pts in CR received maintenance with ponatinib 45 mg po daily with vincristine/prednisone monthly for 2 yrs followed by ponatinib indefinitely. Results: 34 pts with untreated Ph+ ALL and 3 previously treated (1 course) have received a median of 6 cycles; 12 pts are receiving maintenance in CR. Median age was 51 yrs. All pts were in CR after cycle 1. CCyR rates were 94% and 100% after 1 and 2 cycles, respectively. To date, 35 pts (95%) achieved MMR and 26 (70%) CMR. MRD is negative in 35/36 (97%) pts, in whom a sample was sent for assessment. 8 pts received ASCT after a median of 4 courses. Grade ≥ 3 toxicity included infections during induction in 18 pts (49%), increased LFT’s in 13 (35%), thrombotic events in 3 (8%), myocardial infarction (MI) in 3 (8%, 2 unexplained, 1 in the context of sepsis ), skin rash in 4 (11%), and pancreatitis in 6 (16%). With a median follow up of 13 months, 31 pts are alive and in CR; 1 pt died in CR from an unrelated cardiac event after being taken off therapy and placed on imatinib, 1 from MOF (C2D13), 1 from NSTEMI (C2D41), 1 from potential MI (C4D42), 1 from head injury sustained after a fall (C4D13), and 1 from sepsis post ASCT. At the last follow-up, 7 pts (19%) are alive post ASCT; 15 pts (41%) on ponatinib at 15 mg daily in 14, and 30 mg daily in 1; Of the other 9 alive pts, 7 were switched to dasatinib, 1 was switched to imatinib, and 1 is no longer receiving treatment. The 1-year PFS and OS rates were 100% and 86%, respectively. Conclusions: Combination of hyperCVAD + ponatinib is highly effective in pts with Ph+ ALL. Due to the vascular events observed, some pts switched to alternative TKI; in the remaining, ponatinib dose was modified to 30 mg daily during consolidation with subsequent reduction to 15 mg in pts in CMR. Clinical trial information: NCT01424982.