High Efficacy and Particular Safety Profile of Imatinib Mesylate (Glivec®) in Elderly Patients with CML in Chronic Phase: Results of the AFR04 Prospective Study.

The reported median age of the chronic myelogenous leukaemia (CML) patients (pts) enrolled in the pivotal IRIS trial was 50y. Subgroup analysis have been already published focusing on pts over 60y with the conclusion that imatinib is efficient and well tolerated. We report here the first prospective study dedicated to imatinib in elderly pts with CML in chronic phase (CP). Patients aged 70y and over were eligible if they were diagnosed with CP CML for less than 12 months. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) comorbidity index was calculated for all pts. Hydroxyurea was the only treatment accepted before inclusion. Imatinib mesylate (IM, Novartis Pharma) was administered at the dosage of 400 mg QD. Cytogenetic response was assessed for each patient every 6 months during 2 years and every year thereafter. BCR-ABL analysis were performed in reference laboratories every 3 months and results expressed according to the ENL recommendations. Thirty pts with newly diagnosed CP CML were enrolled from March 2002 to October 2004. Median age was 74.8 years (70 to 90). Sex ratio (M/F) was 1.72. Thirty percent of the pts were classified as high risk, 35% intermediate risk and 35% low risk according to the Sokal score stratification. The mean severity CIRS-G index value was 1.47. Two pts had categories at level 3 (cardiopathy and nephropathy). Interval between diagnosis and imatinib initiation was 51 days (13 to 312). Median follow up was 45 months. Grade 2 to 3 neutropenia was observed in 22% of the patients (one patient received G-CSF). Grade 2 to 3 anemia was noted in 31.8% of the pts, 86% of them received rHU-EPO with a complete resolution of anemia. The most commonly reported extra haematological toxicity was oedema (71%, only one grade 3) followed by gastrointestinal symptoms (38%). Of note, 65% of the pts had cardiovascular comorbidities. The 2 pts who presented a cardiac failure episode were those with a CIRS-G cardiac categorie at level 3. Three pts stopped IM (2 already mentioned for cardiac intolerance and one for cutaneous intolerance). The median daily dose of IM was 392 mg (256 to 445), as calculated from the patients records. A transient or permanent dosage reduction was noted in 52.3% of the patients. Cumulative incidence of complete cytogenetic response (CCR) was 71.4% and 77% at 12 and 24 months respectively. One patient lost CCR after imatinib discontinuation. The cumulative incidence of major molecular response (MMR) was 25%, 56% and 59% at months 12, 24 and 36 respectively. Among pts in MMR at month 36, 25% were in complete molecular response. There was no correlation between the CIRS-G score or index and response. Among the 3 pts who stopped the treatment, 2 had CIRS-G categories at level 3. In conclusion, the toxicity of imatinib mesylate appeared more pronounced on the red cell lineage in elderly patients that reported in younger patients. Oedema are also very common but easily treated with diuretics. We observed 2 cases of cardiac failure in this cohort of high risk patients in the 2 patients with a previous level 3 CIRS-G category, suggesting a non favourable benefit/risk ratio in patients with severe comorbidity. For all other elderly patients, a high level of sustained cytogenetic and molecular responses was observed irrespective of age.