Long-Term Results of the OPTIC Trial in CML

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EP: 3.Long-Term Results of the OPTIC Trial in CML

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This is a synopsis of a Peer Exchange series featuring James K. McCloskey, MD, and Lori A. Leslie, MD, of John Theurer Cancer Center, Hackensack University Medical Center.

Shifting focus to chronic myeloid leukemia (CML), James K. McCloskey, MD, Chief of the Leukemia Division at the John Theurer Cancer Center, notes that while the majority of CML patients respond well long-term to tyrosine kinase inhibitors (TKIs), some develop resistance or intolerance, requiring alternate options like ponatinib. Previously, the phase 2 PACE trial explored ponatinib across CML stages and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Though effective, vascular toxicity concerns prompted ponatinib’s temporary removal from the market. However, many clinicians observed lower side effect rates with reduced ponatinib doses, necessitating additional evidence.

The phase 3 OPTIC trial fulfilled this need, randomizing chronic-phase CML patients with TKI resistance/intolerance to starting doses of ponatinib at 45 mg, 30 mg, or 15 mg daily. Once achieving molecular response, patients were dose-reduced to 15 mg with the goal of maintaining efficacy while lowering cumulative exposure and subsequent toxicity risks. Updated OPTIC data at the 2022 ASH Annual Meeting provided key 2-year safety information from all 283 treated patients. While the 45 mg cohort showed the fastest and most robust responses, confirming this as the ideal starting dose, critically, no increases occurred in cardiovascular adverse event rates. Rates remained consistent across prior analyses and the 45 mg versus 30 mg arms.

Specifically, at 4 years, 60% of 45 mg-initiated patients achieved deep molecular responses, with >70% progression-free survival across ponatinib arms at 2 years and ~90% overall survival. Thus, ponatinib’s risk-benefit profile supports its use as standard-of-care for T315I mutated CML, complementing next-generation TKIs like asciminib which lack efficacy in this mutation. Per Dr. McCloskey, OPTIC’s longer-term safety data reassures current real-world practices of initiating ponatinib at 45 mg and de-escalating upon response. With careful cardiac monitoring, dose-optimized ponatinib remains imperative for these difficult-to-treat patients.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.