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Phase II study of combination of hyperCVAD with ponatinib in frontline therapy of patients (pts) with Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by Susan Mary O'Brien:
Early clinical activity and pharmacodynamic effects of duvelisib, a PI3K-δ,γ inhibitor, in patients with treatment-naïve CLL.Meeting: 2015 ASCO Annual Meeting | Abstract No: 7074
Factors influencing outcomes in patients (Pts) with relapsed/refractory b-precursor acute lymphoblastic leukemia (r/r ALL) treated with blinatumomab in a phase 2 study.Meeting: 2015 ASCO Annual Meeting | Abstract No: 7057
Fludarabine, cyclophosphamide, and multiple-dose rituximab as frontline therapy for chronic lymphocytic leukemia.Meeting: 2015 ASCO Annual Meeting | Abstract No: 7042
Educational Book Articles by Susan Mary O'Brien:
- Source: 2010 Educational Book
Presentations by Susan Mary O'Brien:
Meeting: 2011 ASCO Annual Meeting
Session: Chronic Lymphocytic Leukemia Therapy: An Update on Frontline and Novel Therapies (Education Session)
Meeting: 2010 ASCO Annual Meeting
Session: Personalizing Therapeutic Approaches to Chronic Lymphocytic Leukemia (Education Session)