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Lower intensity treatment regimen displays efficacy in older patients with AML
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Treatment with clofarabine and low-dose cytarabine alternating with decitabine was well tolerated and highly effective in older patients with acute myeloid leukemia, according to the results of a phase 2 study.
“Although intensive chemotherapy with anthracyclines and higher doses of cytarabine are considered standard treatment for most younger patients with AML, a significant proportion of patients older than 60 years may not benefit from this approach,” Tapan M. Kadia, MD, of the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Along with higher rates of comorbidities and organ dysfunction in older patients, AML in this population is associated with adverse features, lower rates of complete remission, shorter durations of complete remission and higher early morbidity.”
AML is most commonly seen in older populations. Highly effective, less toxic treatments are needed to serve this population, according to study background.
Kadia and colleagues evaluated data from 118 older patients with recently diagnosed AML. The median age of the population was 68 years (range, 60-81) and 36% were women.
Patients received an induction regimen of 20 mg/m2 IV clofarabine (Clolar, Genzyme) on days 1 through 5 and subcutaneous low-dose (20 mg) cytarabine twice daily on days 1 through 10.
Patients who achieved a response to treatment received a maintenance regimen consisting of three cycles of clofarabine and low-dose cytarabine alternating with three cycles of decitabine for up to 17 cycles.
The primary objective of the trial was to determine the treatment’s effect on RFS and OS.
Median follow-up was 41.4 months. Patients received a median of three cycles (range, 1-19) of therapy.
The overall response rate was 68% (n = 80), which included a 60% (n = 71) complete remission rate. Eight patients achieved a complete remission with incomplete platelet recovery, and one additional patient achieved a partial remission. The researchers noted a comparable proportion of patients aged 60 to 69 years or at least 70 years achieved a complete or partial remission.
Median OS was 11.1 months. Patients who achieved a complete remission or a complete remission with incomplete platelet recovery demonstrated a median OS of 18.5 months, whereas patients who did not achieve a complete remission or a complete remission with incomplete platelet recovery demonstrated a median OS of 4.2 months (P < .001).
Patients who achieved a complete remission with or without incomplete platelet recovery demonstrated a median RFS of 14.1 months.
A greater proportion of patients with a diploid karyotype achieved a complete remission than patients with an adverse karyotype (71% vs. 50%; P = .05) or who were treated for a prior antecedent hematologic disorder (33%; P = .01).
Treatment was well tolerated in the patient population, although 41% of patients experienced grade 3 or grade 4 infections and 61% experienced febrile neutropenia. Other frequently observed toxicities included nausea (81%), elevated liver transaminases (64%), rash (56%), elevated bilirubin (47%) and diarrhea (19%). The most common reasons for treatment discontinuation included refractory disease/inadequate response (34%), relapse (27%) and allogeneic stem cell transplantation (14%).
The researchers acknowledged the lack of a comparison arm is a limitation to these results.
“The combination of clofarabine and low-dose cytarabine alternating with decitabine in a prolonged consolidation/maintenance program is well tolerated and highly effective in older patients with AML,” Kadia and colleagues concluded. “Further studies expanding this strategy and prospectively comparing it with existing higher and lower intensity therapies in older adults are needed.” – by Cameron Kelsall
Disclosure: Kadia reports no relevant financial disclosures. Other researchers report research and institutional funding from Amgen, ARIAD, Bristol-Myers Squibb, Genzyme Inc. and Novartis.
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