During the 2023 European Haematology Association (EHA) congress, new combination strategies for the treatment of patients with chronic myeloid leukaemia were explored. In the frontline, results from the TIGER trial showed that combining nilotinib with pegylated interferon gamma 2b (PEG-IFN) improves molecular responses but comes with some tolerability issues.
The phase 3 TIGER trial compared nilotinib monotherapy to nilotinib in combination with pegylated interferon gamma 2b (PEG-IFN) as first-line treatment for patients with chronic phase chronic myeloid leukaemia (CP-CML), followed by a maintenance phase with nilotinib or IFN, respectively. In the induction phase, 692 patients were randomly assigned to either nilotinib (353 patients) or nilotinib plus PEG-IFN (339 patients). Patients who achieved a confirmed major molecular response (MMR) after at least 24 months of therapy proceeded to the maintenance phase. In this phase, patients who initially received nilotinib continued with nilotinib, while those who received the combination treatment switched to only PEG-IFN. Patients who had ≥12 months of MR4 and ≥36 months of total treatment entered the discontinuation phase. The co-primary endpoints included the MMR rate at 18 months after starting of the induction phase, and the MMR rate at 12 and 24 months after discontinuation of nilotinib and IFN.
After a median follow-up of 6.4 years, the trial reported an estimated 8-year overall survival rate of 95% and an 8-year progression-free survival rate of 93% in both treatment groups. In total, 84% of patients achieved MMR at 18 months, with rates of 81% in the nilotinib group and 88% in the combination group. The combination therapy showed a significant advantage in achieving deep molecular responses (DMR) at MR4 and MR4.5. The probability of maintaining MMR at 12 months after discontinuation was reported as 64%, with rates of 60% and 69% for the nilotinib and combination groups, respectively. Out of 313 evaluable patients, 200 patients are still in MMR (104 from the nilotinib group and 96 from the combination group). Additionally, 76 patients entered treatment-free remission (TFR) after PEG-IFN maintenance. The 2-year probability of maintaining MMR after nilotinib plus IFN combination therapy was estimated at 86%. Adverse events (AEs) of grade 3-5 occurred in 54% vs. 60% of patients in the nilotinib monotherapy and combination group, respectively. Specific AEs of interest included arteriovascular events (9% vs. 6%), fatigue (2% vs. 4%), thrombocytopenia (8% vs. 8%), and alanine aminotransferase (ALAT) increase (4 vs. 9%).
In conclusion, the TIGER trial showed that the combination of nilotinib with PEG-IFN improves molecular responses but comes with some tolerability issues. PEG-IFN maintenance did not significantly enhance long-term TFR. However, selected patients who achieved MMR after the combination therapy, maintained MR4 on PEG-IFN monotherapy, and discontinued PEG-IFN after at least 1 year in MR4 were likely to maintain MMR in TFR.
Reference
Hochlaus A. Nilotinib vs. nilotinib + PEG-interferon alpha induction and nilotinib or PEG-interferon alpha maintenance therapy for newly diagnosed chronic myeloid leukemia patients. the tiger trial. Presented at EHA 2023; Presentation ID S157
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