Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV

Abstract

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874

Fig. 1

Flow diagram of randomized and evaluable patients. n number of patients, IM400 imatinib 400 mg/day, IM800 imatinib 800 mg/day, CML chronic myeloid leukemia, CP chronic phase, IC informed consent, OS overall survival, IM imatinib, y years, CCR complete cytogenetic remission, MMR major molecular remission, MR ⁴ molecular remission ≤0.01 % on the international scale

Fig. 2

Molecular and cytogenetic remissions according to treatment groups. a Cumulative incidences of MMR, b cumulative incidences of MR⁴, and c cumulative incidences of CCR. MMR major molecular remission, MR ⁴ molecular remission ≤0.01 % on the international scale, CCR complete cytogenetic remission, n number of patients, IM400 imatinib 400 mg/day, IM800 imatinib 800 mg/day, ns not significant

Fig. 3

Progression to AP and BC according to treatment groups. AP accelerated phase, BC blast crisis, n number of patients, CI cumulative incidence, IM400 imatinib 400 mg/day, IM800 imatinib 800 mg/day, ns not significant