130076-144

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

Subcategory: 
Category: 
Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
General Poster Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 

7064

Citation: 

J Clin Oncol 32:5s, 2014 (suppl; abstr 7064)

Author(s): 

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


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

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.