Nilotinib Plus Pegylated Interferon Alfa-2a Promotes Deep Molecular Response in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Clinical Summary:

• Design/Population: The phase 3 PETALs trial randomized patients with newly diagnosed chronic phase chronic myeloid leukemia to receive nilotinib either alone or with pegylated interferon alfa-2a for up to 2 years.
• Key Outcomes: Nilotinib plus pegylated interferon alfa-2a increased early deep molecular response rates compared with nilotinib alone. Hematologic and vascular toxicities were similar between arms, but psychiatric adverse events were reported and require close monitoring.
• Clinical Relevance: Adding pegylated interferon alfa-2a to nilotinib may deepen early molecular responses, but the benefit must be balanced against added toxicity and the need to determine whether deeper responses translate into durable treatment-free remission.

Results from the phase 3 PETALs trial demonstrated that adding pegylated interferon alfa-2a to nilotinib improved early deep molecular response compared with nilotinib alone among patients with newly diagnosed chronic phase chronic myeloid leukemia (CML). 

“Second generation tyrosine kinase inhibitors (TKIs) have improved response rates in patients with chronic phase CML,” stated Franck Nicolini, MD, Centre Léon Bérard, Lyon, France, and coauthors. “Phase 2 trials demonstrated increased deep molecular response rates when combining second-generation TKIs with pegylated interferon alfa.” 

In this multicenter, open-label trial, 200 patients were randomized 1:1 to receive 300 mg of twice daily nilotinib either alone (n = 99) or in combination with 30 μg of pegylated interferon alfa-2a once weekly for the first month followed by 45 μg for up to 2 years (n = 101). The primary end point was cumulative molecular response. A key secondary end point was safety. 

At a median follow-up of 67 months, the 12-month cumulative molecular response rate was 15% in the nilotinib arm and 24% in the nilotinib plus pegylated interferon alfa-2a arm (P = .048). 

Grade 3/4 hematologic adverse events were reported in 14 patients in each treatment arm. Severe thrombocytopenia without hemorrhage was reported in 5 patients in the nilotinib arm and 6 patients in the nilotinib plus pegylated interferon alfa-2a arm. Grade 3/4 psychiatric adverse events were reported in 5 patients (with 1 unsuccessful suicide attempt) and 6 patients (with 3 unsuccessful suicide attempts), respectively. Grade 3/4 vascular events were reported in 6 patients in the nilotinib plus pegylated interferon alfa-2a arm and 5 patients in the nilotinib arm (7 total events). 

“In this setting, [pegylated interferon alfa-2a] combined with nilotinib induced higher initial rates of [cumulative molecular response] compared to TKI monotherapy, despite additional side effects,” concluded Dr Nicolini et al. “Whether this early molecular response translates into sustained treatment-free survival should be studied in a randomized trial sufficiently powered for this outcome.”

Source:

Nicolini FE, Etienne G, Huguet F, et al. Final results of nilotinib versus nilotinib combined with pegylated interferon alfa-2a as first-line therapy in chronic phase chronic myeloid leukaemia in France (PETALs): An open-label, multicentre, randomised phase 3 trial. Lancet Haematol. Published online: May 2026. doi:10.1016/s2352-3026(26)00043-8