Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome‐positive chronic myelogenous leukemia

Abstract

BACKGROUNDOlder age is a consistent poor prognostic factor in patients with Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML). Whether this is related to an intrinsic worse disease biology or to inadequate drug delivery or excessive treatment‐associated toxicity is unknown. The availability of imatinib mesylate, a selective, Bcr‐Abl‐targeted therapy that is administered orally with minimal side effects, may clarify whether older age would remain an adverse factor (thus, implying a different age‐related CML biology).METHODSSeven hundred forty‐seven patients in different phases of Ph‐positive CML who were treated with imatinib from 1999 until the time of last follow‐up were evaluated. Among them, 187 patients had newly diagnosed, early chronic phase CML; 351 patients had chronic phase CML after interferon α (IFN) failure; 133 patients had accelerated phase CML; and 76 patients had blastic phase CML. The imatinib daily dose varied from 400 mg to 800 mg orally, according to the protocol design. Patients were categorized into a group of older patients (age 60 years or older) or younger patients (age younger than 60 years). Their characteristics, responses to therapy, and survival were compared by univariate and multivariate analyses.RESULTSOne hundred eighty‐seven patients had newly diagnosed CML, and 49 patients (26%) were in the older age group. Older patients had similar cytogenetic response rates and survival compared with younger patients. Among 351 patients with late chronic phase CML after IFN failure, 120 patients (34%) were in the older age group. Although the older patients had a lower incidence of achievement of complete cytogenetic response (Ph, 0%) by univariate analysis (56% vs. 44%; P = 0.05), age was not found to be an independent poor prognostic factor in the multivariate analysis. Similarly, older age was not an adverse poor prognostic factor for survival. Forty‐two of 133 patients (32%) with accelerated phase CML were older. The incidence of any cytogenetic response was lower in older patients (53% vs. 33%; P = 0.04), but age was not significant in the multivariate analysis. Older patients also had a trend toward worse survival (P = 0.09) that was not significant in the multivariate analysis. Twenty‐eight of 76 patients (37%) evaluated in blastic phase were older. Older age was not a significant prognostic factor either for achieving response or for survival.CONCLUSIONSWith imatinib therapy, older age appears to have lost much of its prognostic relevance. This suggests that the previous poor prognosis observed with older age was related to treatment‐associated factors (e.g., toxicity with allogeneic transplantation or with IFN therapy) rather than to an intrinsic, different disease biology of CML in older patients. Cancer 2003;98:1105–13. © 2003 American Cancer Society.DOI 10.1002/cncr.11629

Long‐term safety and efficacy of imatinib mesylate (Gleevec®) in elderly patients with chronic phase chronic myelogenous leukemia: Results of the AFR04 study

“…Interferon doses used to achieve response were lower in older patients, and adverse events were similar in both age groups. With the use of IM, older age appears to have lost much of its prognostic relevance, suggesting that the poor prognosis previously observed with older age was related to treatment-associated factors rather than to the biology of CML in older patients [13].…”

Recent trends in long-term survival of patients with chronic myelocytic leukemia: disclosing the impact of advances in therapy on the population level

“…This improvement is especially notable in the younger patient populations, but there is reason to expect that improvement in survival will extend to older populations as further experience in the use of TKIs for CML is accumulated 24,25 and studies delineate the safest and most effective ways to use them in older patients. Relative survival for younger patients with CML who have survived for five years is greater than 90%, suggesting that late progression is becoming a rarer event in CML and that the course of the disease may be significantly delayed.…”

Impact of age on the outcome of patients with chronic myeloid leukemia in late chronic phase: results of a phase II study of the GIMEMA CML Working Party

“…Older patients had a lower probability of CHR (53%) compared to younger ones (74%). Cortes et al 18 reported a higher probability of CHR (94%) in both groups of patients using the same criteria to define a CHR. The differences in CHR rates probably reflect a difference in the ability to assure high dose intensity between a single, very experienced center and a multi-institutional, national trial.…”

“…[8][9][10][11][12][13][14][15][16] Moreover, a major cytogenetic response is currently achieved in more than 80% of patients with early chronic phase disease and in more than 50% of those with late chronic phase disease. 17 In their series, Cortes et al 18 showed that imatinib eliminated the negative effect of age on response and survival. Within the frame of a large phase II trial of the GIMEMA CML Working Party, 19 which enrolled 284 late chronic phase patients treated with imatinib (400 mg daily) after interferon failure, we evaluated responses, progression-free and overall survival and compliance in patients younger and older than 65 years of age at enrollment.…”