PHILADELPHIA-Chronic myeloid leukemia (CML) patients treated with imatinib mesylate (Gleevec) reported better quality of life (QOL) than those on interferon/cytarabine, and those who switched from interferon/cytarabine to imatinib reported improved QOL, compared with those who remained on interferon, Elizabeth A. Hahn reported. This is clinically important because about 20% of CML patients drop out of interferon treatment within 6 months due to intolerable adverse effects.
PHILADELPHIAChronic myeloid leukemia (CML) patients treated with imatinib mesylate (Gleevec) reported better quality of life (QOL) than those on interferon/cytarabine, and those who switched from interferon/cytarabine to imatinib reported improved QOL, compared with those who remained on interferon, Elizabeth A. Hahn reported. This is clinically important because about 20% of CML patients drop out of interferon treatment within 6 months due to intolerable adverse effects.
In an oral presentation at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 346), Ms. Hahn discussed QOL studies in 1,106 patients with chronic phase CML randomized to either imatinib or interferon/cytarabine in the IRIS (International Randomized IFN vs STI571) trial. The QOL analyses were done by Ms. Hahn and her colleagues from Evanston Northwestern Healthcare’s Center on Outcomes, Research and Education, and from Novartis Pharmaceuticals Corporation.
Ms. Hahn, who is director of biostatistics at the center, said that QOL was a secondary endpoint in the trial protocol and that 95% of patients participated in the QOL study. "Quality of life is an important endpoint because it captures multiple aspects of the patient’s own assessment of the effect of disease," she said. QOL was assessed using the Functional Assessment of Cancer Therapy-Biological Response Modifiers (FACT-BRM). The primary QOL endpoint was the Trial Outcome Index, a measure of physical well-being, functional well-being, and treatment-specific features. Social/family and emotional well-being were also evaluated. Ms. Hahn reported analysis of questionnaires from 530 patients initially randomized to imatinib and 519 initially randomized to interferon/cytara-bine. Statistical analysis was based on intention to treat.
"We found that the imatinib patients largely preserved their baseline QOL but that after the first month on interferon/cytarabine, patients had a sharp drop in the Trial Outcome Index and never did recover to baseline (P < .001)," Ms. Hahn said (see Figure).
The researchers considered a 5-point difference in the Trial Outcome Index as being clinically important. "We saw a 17-point difference between patients treated with imatinib and those treated with interferon/cytarabine, indicating that the QOL effect is highly clinically important as well as statistically significant," Ms. Hahn said. Overall, patients on imatinib reported better daily functioning and well-being, less fatigue, milder emotional and cognitive problems, and fewer side effects, compared with those on interferon/cytarabine.
During 18 months of treatment, 261 patients crossed over from interferon/cytarabine to imatinib. When this subgroup was analyzed, they showed a fast improvement in the Trial Outcome Index. "The crossover patients immediately experienced an improvement in all QOL endpoints. Their Trial Outcome Index scores remained statistically different from patients who had been on imatinib throughout, but the difference was narrowing and at 18 months, it was less than the 5-point difference considered clinically meaningful," she said. The investigators concluded that there are large statistically significant and clinically important differences in the primary QOL endpoint that favor imatinib out to 18 months of treatment in chronic phase CML. Social/family and emotional well-being were also better on imatinib.
During the discussion period, Peter Bross, MD, a medical officer in the FDA’s Division of Oncology, raised questions about the design of the study. Dr. Bross asked whether the QOL instrument had included questions on imatinib-related side effects and how the investigators determined that a 5-point difference in the Trial Outcome Index was clinically significant. Ms. Hahn noted that the questionnaire included items on nausea, pain, and fatigue, and acknowledged that it did not include specific questions on edema or rash. She said that analyses of changes in performance status as well as patient-reported Global Ratings of Change (collected in US patients only) suggested that a 4- to 6-point change was clinically important. Given that the standard error of measurement was 4 points, a 5-point criterion was chosen.