CML Treatment in the Elderly

Abstract & Commentary

Synopsis: In a 4-year review of chronic myelogenous treatment responses with imatinib mesylate at a single institution, older patients were found to have comparable outcomes to younger patients. An implication of this finding is that this disorder is not biologically more resistant in the elderly and that nontoxic and effective treatment, such as with imatinib mesylate, is likely to produce meaningful responses at all ages.

Source: Cortes J, et al. Cancer. 2003;98:1105-1113.

Older age has been considered a negative prognostic factor in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML), either due to inherent biological differences in the disease in older patients or a perceived or real inability of older patients to receive adequate treatment. However, with the availability of imatinib mesylate as first-line therapy, a larger number of older patients are receiving this less toxic, but effective, therapy. The current report is a retrospective analysis of recently treated elderly CML patients in an effort to determine if there remains an age disadvantage in survival.

Of a total of 747 patients with CML evaluated and treated (from 1999 to date) with imatinib mesylate in the Leukemia Department of the University of Texas M.D. Anderson Cancer Center, approximately one-third were considered in the "older" age group (age 60 years and older). Of these, 187 patients had newly diagnosed, early chronic-phase CML; 351 patients had chronic phase CML after interferon a failure; 133 patients had accelerated-phase CML; and, 76 patients had blastic phase CML. Imatinib mesylate was used in doses ranging from 400 mg to 800 mg daily, depending on the phase of disease and prior treatments. Of the 187 patients with newly diagnosed, early chronic-phase disease, 49 (26%) were in the older age group. The older patients had similar cytogenetic response rates and survival when compared with younger patients. Among 351 patients with late chronic-phase CML after interferon a failure, 120 patients (34%) were in the older age group. Although the older patients had a lower incidence of achievement of complete cytogenetic response by univariate analysis (56% vs 44%; P = .05), age was not found to be an independent poor prognostic factor in the multivariate analysis. Similarly, older age was not an adverse prognostic factor for survival in this group. Of the 133 patients with accelerated phase disease, 42 (32%) were in the older group. By univariate analysis, the incidence of any cytogenetic response was less in this group (53% vs 33%; P = .04), but age was not an independent adverse prognostic indicator by multivariate analysis. Of the 76 patients in blastic phase, 28 (37%) were in the older age group, and older age was not a significant prognostic factor either for achieving response or for survival.

Comment by William B. Ershler, MD

Chronic myelogenous leukemia is a disease that occurs most frequently in older people, and survival has been found to be reduced in patients of advanced age.1,2 Among the reasons that might explain this, 2 seem most likely. Like acute myelogenous leukemia (AML), the disease might actually be somewhat different in older people, and perhaps more resistant to chemotherapy. Older individuals with AML more typically present with an antecedent myelodysplastic syndrome, cytopenias and marrow cytogenetic abnormalities.3 Cytoreductive treatment in these patients has been unsatisfactory and is generally not recommended, unless in an investigational setting.4 Thus, it is conceivable that similar factors explain the negative effect of age on CML outcomes. The current report, however, would speak to another explanation. In this review, it is apparent that older patients, treated with the less toxic imatinib mesylate, fared comparably well as younger patients. Although there were differences detected in univariate analysis, these turned out to be not a factor of age when analyzed by multivariate methodology, perhaps reflecting the influence of age-associated comorbidities.

This report is a good reflection of what is likely to be found with other tumors in older patients. The tumors are not a priore, more resistant in older patients. Instead, the differences in survival may result from less therapy, either because of a presumed likely greater toxicity, or for some other bias that precludes effective management in geriatric cancer patients.

Dr. Ershler is INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.

References

1. Sokal J, et al. Blood. 1984;63:789-799.

2. Hasford J, et al. J Natl Cancer Inst 1998;90:850-858.

3. Taylor P, et al. Leukemia. 1995;9:231-237.

4. Burnett AK, Eden OB. Lancet. 1997;349:270-275.