Imatinib in the Treatment of CML Patients ≥ 65 Years Old in Late Chronic Phase: Results of a Phase II Study of the GIMEMA CML Working Party.

Abstract

Older age constitutes a poor prognostic variable in CML patients: the negative effect of age on long-term survival has been consistently observed with most effective therapeutic modalities, both drug therapies (busulfan, hydroxyurea and interferon) and allogeneic transplant. In particular, older patients treated with interferon experienced much more adverse events than younger ones. In part their poorer prognosis was probably due to poor treatment compliance and few older patients have been included in prospective studies of interferon. Actually, imatinib is the first-line treatment for CML: its efficacy is very high and it seems to be well tolerated across age groups. We performed a sub-analysis of the effects of age on response and tolerance within the phase II trial of the italian GIMEMA CML Working Party (serial n.CML/002/STI571), which included 284 late chronic phase patients, treated with imatinib (400 mg daily) after interferon failure. Following the WHO, who defines “old” a patient ≥ 65 years, we analyzed the safety and efficacy of imatinib by age group: 226/284 patients (80%) were < 65 years (extr. 17–64) and 58/284 (20%) were ≥ 65 years (extr. 65–85 yrs) old. No significant differences between the two age groups were present at enrollment. Table 1 shows the responses and incidence of hematologic and non-hematologic adverse events (AEs). As expected, older patients experienced more AEs, both hematologic and non-hematologic. In part this significantly poorer tolerance probably justifies the lower response rates, both hematologic and cytogenetic. However, the overall survival was not different between the two age groups: with a median observation time of 33 months, the overall survival curves were superimposed (91%). Moreover, the rate of progression to accelerated/blastic phase was the same (10%). This study demonstrates that imatinib is greatly effective in older CML patients in late chronic phase (53% of MCR and 36% of CCR) and allows a good long-term survival. It is conceivable that treating old CML patients at the onset of the disease, as already shown by Jorge Cortes et al (Cancer 2003; 98:1105), could translate into response rates as the ones of younger patients.Responses and adverse events≥ 65 (n. 58)≤ 65 (n226)p valueComplete Hematologic response91%99%0,001Major Cytogenetic Response53%74%0,003Complete Cytogenetic Response36%57%0,001Grade III Hematologic AEs72%50%0,002Grade III+IV Hematologic AEs86%60%0,0001Grade II non Hematologic AEs83%68%0,0001Grade III + IV non Hematologic AEs29%10%0,0001