Treatment Optimization By High-Dose Imatinib: Randomized Comparison Of Imatinib 800 Mg Versus Imatinib 400 Mg +/- Ifn In Newly Diagnosed Bcr-Abl Positive Chronic Phase (Cp) Cml: The German Cml-Study Iv.

6517 Background: Initial imatinib therapy has never been optimized. Methods: Therefore, in the CML Study IV imatinib 800 mg (IM 800) was compared with imatinib 400 mg ± IFN (IM 400, IM+IFN) in newly diagnosed, not pretreated CML for molecular and cytogenetic remissions at 12 months, overall (OS) and progression-free survival (PFS) and toxicity. Results: By April 30, 2009, 1015 CP patients have been randomized (326 for IM 400, 338 for IM 800, 351 for IM+IFN). The median daily doses were 646 (209-800) mg in the IM 800 and 400 (184-720) mg in the IM 400 ± IFN arms. The cumulative incidences (cum. inc.) of CCR and MMR with IM 400, IM 800 and IM+IFN are shown in the Table. MMR at 12 months was reached in more patients with IM 800 than with IM 400 (p<0.01) or IM+IFN (p<0.01). Optimal molecular response was reached with IM 800 after a median of 31.3 months vs. 42.5 with IM 400 and 47.5 with IM + IFN. Also CCR was reached faster with IM 800 (p<0.01). The more rapid achievement of MMR with IM 800 was observed in low and intermediate risk patients, but not in high risk patients. Patients receiving more than 600 mg/day reached remissions faster than those receiving less (CCR after a median of 7.8 vs. 8.9 months, MMR after a median of 10.4 vs. 12.9 months). OS (92%) and PFS (88%) at 5 years showed no difference between treatment arms. With individual dose adjustments IM 800 was well tolerated. Grade III/IV AEs were rare and did not differ between treatment arms. Conclusions: These data show a significantly faster achievement of MMR and CCR with IM 800 as compared to IM 400 ± IFN. The data indicate that the optimal imatinib dose in CP may be higher than 400 mg/day. Longer observation is required to determine whether this faster achievement of MMR and CCR will translate into better OS or PFS. Time after start of treatment Cum. inc. CCR (%) MMR (%) IM400 n=273 Δ IM800 n=268 Δ IM+IFN n=304 IM400 n=279 Δ IM800 n=283 Δ IM+IFN n=309 6 mo 21.5 12.0 33.5 15.1 18.4 6.1 11.3 17.4 11.2 6.2 12 mo 49.8 13.4 63.2 13.7 49.5 31.1 24.7 55.8 22.8 33.0 18 mo 66.6 7.2 73.8 3.8 70.0 51.5 18.7 70.2 15.5 54.7 24 mo 74.5 8.5 83.0 6.6 76.4 64.2 13.3 77.5 14.7 62.8 Δ: Difference between IM 800 and IM 400 or IM 800 and IM+IFN, respectively. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Deutsche José-Carreras Leukämiestiftung, Deutsche Krebshilfe, Deutsches Kompetenznetz für Akute and Chronische Leukämien, Essex Pharma, European LeukemiaNet, Novartis, Roche, Grenzach-Wyhlen, Germany