Frontline ibrutinib and rituximab plus fludarabine, cyclophosphamide, and rituximab improved quality of life in patients with chronic lymphocytic leukemia; ibrutinib given continuously maintained the improved quality of life, and it did not decline over time.
Frontline ibrutinib (Imbruvica) and rituximab (Rituxan; IR) plus fludarabine, cyclophosphamide, and rituximab (FCR) improved quality of life in patients with chronic lymphocytic leukemia (CLL); ibrutinib given continuously maintained the improved quality of life, and it did not decline over time.
“The results of this quality-of-life analysis support the use of frontline Ibrutinib in previously untreated younger CLL patients,” said lead investigator Priyanka Pophali, MD, assistant professor at the University of Washington Carbone Cancer Center, during a presentation of the findings at the 2021 American Society of Hematology Annual Meeting & Exposition.
The randomized, phase 3 ECOG-ACRIN clinical trial E1912 established IR as the standard of care for patients with CLL age 70 or younger in the frontline setting, and quality of life was a secondary endpoint. Investigators compared continuous IR with time-limited FCR therapy, “due to the differing profile of treatment-related toxicities over the short and long-term,” Pophali explained.
Patients who were enrolled in the trial completed the Functional Assessment of Cancer Therapy-General (FACT-G) and Leukemia subscale at randomization (baseline), 3, 6, and 12 months post-randomization, and every 6 months for 2 years regardless of disease status.
Investigators measured the primary outcome with the FACT-Leukemia Trial Outcome Index (TOI), which is a 31-item questionnaire with scores ranging from 0 to 124.
“The FACT-Leukemia trial outcome index is a summation of the factsheet physical well-being, functional well-being, and leukemia subscales,” Pophali said.
The primary endpoint was the difference in FACT-Leukemia TOI change scores from randomization to 12 months between patients treated with continuous therapy (arm A) and patients treated with time-limited therapy (arm B). Comparisons between the treatment arms were performed using two-sample t tests; linear mixed effects models were used to estimate the trajectories of patient-reported outcome (PRO) scores.
The PRO data was provided at baseline and 12 months for 65.8% of patients in arm A and 67.4% in arm B.
At enrollment, there were no significant differences in the baseline FACT-Leukemia TOI scores (mean ± SE) between the two arms: A (93.27 ± 1.03); B (92.68 ± 1.38; p=0.73). The FACT-Leukemia TOI score improved from baseline to 12 months in both arms.
The change scores from baseline to 12 months were not significantly different between arm A (7.59 ± 1.09) and arm B (8.22 ± 1.44; p=0.73). Change in FACT-Leukemia TOI from baseline to 3 months was 5.77 ± 0.77 and 4.06 ± 1.18 (p=0.22); and from baseline to 6 months was 6.87 ± 0.87 and 8.01 ± 1.44 (p=0.50) in arm A and arm B, respectively.
The improvement in FACT-Leukemia TOI scores was maintained in both treatment arms after 6 months, with no major difference in total FACT-Leukemia TOI scores between the two arms over the first 36 months.
An analysis of the FACT subscales showed physical well-being improved in arm A (0.37 ± 0.22) and declined in arm B (-0.92 ± 0.39) from baseline to 3 months (p=0.004 for difference in physical well-being change between arms). There were, however, no significant differences in functional well-being and FACT-Leukemia subscales from baseline to 3, 6, and 12 months.
Overall, the results showed that quality of life improvement is maintained during IR continuous therapy, and since the regimen was previously shown to improve PFS and OS over FCR, these findings further support the use of IR in previously untreated patients with CLL, concluded Pophali.
Pophali P, Wang X, Zhao F, et al. Quality of life in patients <= 70 years of age with Chronic Lymphocytic Leukemia treated frontline with Ibrutinib-Rituximab versus Fludarabine Cyclophosphamide Rituximab: Analysis from ECOG-ACRIN E1912. Presented at: 2021 American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Abstract 1562.