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: NCT00055874Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-014-2041-0) contains supplementary material, which is available to authorized users.

Epidemiology of chronic myeloid leukaemia: an update

“…Nevertheless, Proetel et al showed that older patients (≥65 years) responded more slowly to standard dose imatinib (400 mg/day) than younger, but equally well to a higher dose (800 mg/day). Grade 3 and 4 adverse events were similar in both age groups [39]. Clinical implications of these findings are unclear, although the authors suggest that the optimal dose of imatinib for older patients may be higher than 400 mg/day.…”

“…stage, Sokal, Hasford and EUTOS score, aberrant cytogenetics), which are beyond the scope of this overview, several nondisease-related factors might have an impact on the prognosis of CML. A number of studies indicate that, even after the introduction of imatinib in 2001-2002, elderly CML patients (>60-70 years) have an inferior survival than younger ones [28,[36][37][38], although recent reports from UK and the German CML Study IV concluded that the relative survival was almost identical for patients under and over 60 (65)years [9,39]. Possibly, the underuse of imatinib (or other TKIs) in the elderly CML patient populations during the first years after its introduction explains the inferior results in the very elderly population as reported in some population-based studies [8].…”

The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia

“…With the advent of first TKI, namely imatinib, also elderly patients, usually candidate to palliative approach, have been treated and cured [1]. A 5-year relative survival of elderly CML patients (≥65 years) was shown to be comparable to that of younger patients [2]. As recent data from large population-based registries report a median age at diagnosis of 56 years [3], it is reasonable to consider that many of the CML patients currently under treatment have even a greater median age.…”

Chronic myeloid leukemia: reminiscences and dreams

“…79 A subset analysis from this randomized study also showed a greater benefit for patients over 65 years of age. 80 Another recent randomized intergroup phase II study also demonstrated deeper molecular responses in the 800 mg daily arm compared with 400 mg daily, with MR 4 of 25% and 10%, respectively, with a trend for improved progression-free and overall survival, but with substantially more grade 3 and 4 side-effects. 81 There is also some evidence that imatinib 600 mg daily is tolerated in more than 80% of CML patients and results in superior cytogenetic and molecular responses at 12 and 24 months compared to the conventional 400 mg daily dose.…”