Upfront low-dose diet-modified nilotinib versus standard imatinib in Indian patients with newly diagnosed chronic-phase chronic myeloid leukemia: The NILLOW phase II randomised trial.

6584 Background: Upfront use of second-generation tyrosine kinase inhibitors in chronic myeloid leukemia (CML) is limited in resource-constrained settings due to cost, fasting requirements, and tolerability concerns. Food increases nilotinib bioavailability, enabling effective dose reduction. Methods: NILLOW was a single-center, open-label, randomized phase II study. Newly diagnosed CML-CP patients were randomized 1:1 to receive nilotinib 150 mg twice daily with meals or imatinib 400 mg once daily. The primary endpoint was EMR at 3 months (BCR-ABL1 IS ≤10%). Safety and hematologic recovery were evaluated as secondary endpoints. Results: EMR at 3 months was significantly higher with nilotinib compared to imatinib (73.8% vs 46.2%; absolute difference 27.6%; p=0.001). Patients receiving nilotinib demonstrated faster hemoglobin recovery during follow-up (p<0.01). Grade 3/4 anemia was lower with nilotinib (5.5% vs 17.8%; p=0.02). Imatinib was associated with higher rates of peripheral edema, periorbital edema, rash, pruritus, and headache (all p<0.05). Conclusions: Low-dose fed nilotinib improves early molecular response with superior tolerability compared to imatinib. This approach represents a cost-effective frontline strategy for CML in low-resource settings. Further studies as phase 3 maybe be followed up to confirm the signal. Clinical trial information: CTRI/2024/03/064707.