First-line fludarabine not superior to chlorambucil in older CLL patients

In patients aged older than 65 with chronic lymphocytic leukemia, first-line treatment with fludarabine did not demonstrate better survival outcomes when compared with chlorambucil. Fludarabine treatment did however demonstrate improved response rates and longer time to treatment failure.

Due to the underrepresentation of patients aged older than 65 in clinical trials examining fludarabine to treat CLL, researchers from the German CLL Study Group conducted a prospective, multicenter, phase-3 trial to compare chlorambucil (Leukeran, GlaxoSmithKline) treatment with fludarabine treatment.

Ninety-three patients were randomly assigned to fludarabine 25 mg/m² IV for five days every 28 days for six courses; 100 patients were assigned to chlorambucil 0.4 mg/kg, increased to 0.8 mg/kg every 15 days for 12 months.

PFS was similar in the fludarabine group (19 months) and the chlorambucil group (18 months); however, clinical significance was not reached. OS was also similar between the two groups (46 months vs. 64 months), but again, clinical significance was not reached.

Although survival was not improved, the overall response rate was higher in the fludarabine group (72%) vs. the chlorambucil group (51%; P=.003). The complete remission rate was also higher with fludarabine (7%) than with chlorambucil (0%; P=.011). Time to treatment failure was 18 months in the fludarabine group and 11 months in the chlorambucil group.

Grade-3 and -4 myelotoxicity was more frequent in the fludarabine group, according to the researchers.

Eichhorst BF. Blood. 2009;doi:10.1182/blood-2009-02-206185.

This study in the elderly confirms the results of several prior studies, most notably the original study by Kanti Rai of the Cancer and Leukemia Group B, showing that responses were more robust with fludarabine than with chlorambucil, but OS was not impacted. Further, toxicity was greater with fludarabine. These studies buttress the notion of personalized medicine: Treatment often needs to be tailored to the individual patient. The clinician treating CLL should take into consideration both results of these studies and patient morbidities when selecting therapy, particularly for the elderly.

– Morton Coleman, MD
HemOnc Today Editorial Board member

Click here to read perspective on this article from a HemOncToday.com blogger.