Introduction

The discovery of tyrosine kinase inhibitors (TKI) has changed the natural course of CML but limited data exists on long-term efficacy and safety of 2nd generation TKI, imatinib.

Aim

• To evaluate long-term safety and efficacy of imatinib with focus on molecular responses and adverse drug related reactions (ADR).
• Compare the efficacy and ADR profiles of high-dose imatinib, imatinib in combination with interferon ? (IFN) and imatinib monotherapy at standard dose.

Study Methods

Patient Profile

• N=1551
• Newly diagnosed chronic myeloid leukemia (CML) patients with chronic phase

Design

CML-Study IV was a five-arm randomized study

IM=Imatinib
IFN=Interfereon

Primary Endpoint

• Overall survival (OS) was defined as the time between diagnosis and death resulting from any cause.
• Progression-free-survival (PFS) considered the additional events accelerated phase (AP) and blast crisis (BC).

Results

Efficacy

• 10-year progression free and overall survival was 82(79-84) % and 84(82-86) %, respectively.

PFS- progression free survival, OS- overall survival.

• By 10 years 59(55-64)% reached MR⁵, 72(68-78)% MR ^4.5, 81(78-84)% MR⁴, 89(86-90)% MMR and 92(90-94)% MR²
• IM800 had the shortest and IM400 after IFN failure the longest median times to responses

Safety

• 8 years probabilities of adverse drug reactions (ADR) were 76%, of grade (3-4) 22%, of non-hematologic 73% and of hematologic 28%.
• More ADR observed with IM 800mg and IM400 mg plus interferon ? (IFN).
• Most patients had their first ADR early with decreasing frequency later on. No new late toxicity was observed.
• ADR to imatinib were frequent, but mostly mild and manageable, also after treatment optimization with IM800 and combination with IFN

Conclusion

• Deep molecular responses can be achieved at high frequency with imatinib
• The high response rates indicate that imatinib can probably be discontinued in the majority of patients
• ADR to imatinib are frequent, but mostly mild and manageable
• Imatinib continues to be an excellent initial choice of treatment for most patients with CML

Leukemia (2015) 29, 1123–1132