Priyanka A. Pophali, MD, Assistant Professor, Division of Hematology at the University of Wisconsin-Madison. In this video, she speaks about the ASH 2021 Abstract – 1562 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. Dr. Pophali co-authored this study with Lynne I Wagner, Ph.D., and others.
Origins:
In comparison to previous standard chemo-immunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), the ECOG-ACRIN randomized phase 3 clinical trial E1912 established ibrutinib-rituximab (IR) as the standard of care for CLL patients 70 years in the frontline setting by improving progression free (PFS) and overall survival (OS) (Shanafelt et al. NEJM 2019). Because of the different profile of treatment-related toxicities over the short and long term, quality of life (QOL) was an important secondary goal in this trial comparing continuous (IR) with time-limited (FCR) therapy. The results of the E1912 patient-reported outcomes (PROs) are presented here.
Methodologies:
Patients on E1912 completed the Functional Assessment of Cancer Therapy-General (FACT-G) and Leukemia subscales at randomization (baseline), 3, 6, and 12 months after randomization, and every 6 months for the next two years, regardless of illness state. The FACT-Leukemia Trial Outcome Index (FACT-Leu TOI) was the primary outcome, which was derived by adding items from the FACT-G physical wellbeing (PWB), functional well-being (FWB), and leukemia subscales (score range: 0-124). The primary objective was the difference in FACT-Leu TOI change scores between patients treated with continuous therapy Arm A (IR) vs time-limited therapy Arm B from randomization to 12 months (at response evaluation) (FCR). All cases with data at baseline and the relevant time point were used to calculate mean change scores from baseline to each time point. Two-sample t tests were used to make comparisons between treatment arms. The trajectories of PRO scores were estimated using linear mixed effects models.
Findings:
On March 8, 2021, PRO data was extracted. PRO data was given for 233/354 (65.8%) individuals on the IR arm and 118/175 (67.4%) patients on the FCR arm at baseline and 12 months. The baseline FACT-Leu TOI scores (mean SE) for the two arms were not significantly different at enrollment: IR (93.27 1.03) versus FCR (92.68 1.38; p=0.73). In both arms, the FACT-Leu TOI score improved from baseline to 12 months (Table 1 and Figure 1). The primary result, change scores from baseline to 12 months, did not differ substantially between IR (7.59 1.09) and FCR (8.22 1.44; p=0.73). In the IR and FCR arms, the change in FACT-Leu TOI from baseline to 3 months was 5.77 0.77 and 4.06 1.18 (p=0.22), respectively; while the change in FACT-Leu TOI from baseline to 6 months was 6.87 0.87 and 8.01 1.44 (p=0.50).
The improvement in FACT-Leu TOI scores was maintained in both treatment arms after the first 6 months of treatment. Over the first 36 months after registration, there was no significant difference in total FACT-Leu TOI score between the continuous therapy (IR) and time-limited therapy (FCR) arms.
PWB improved in the IR arm (0.37 0.22) but declined in the FCR arm (-0.92 0.39) from baseline to 3 months (p=0.004 for the difference in PWB change between arms), but there was no significant difference between the two arms for change in PWB scores from baseline to 6 and 12 months (p=0.004 for the difference in PWB change between arms). Changes in the FWB and FACT-Leu subscales from baseline to 3, 6, and 12 months were not significantly different between the two arms.
Outcomes:
When CLL patients aged 70 and younger are treated with IR or FCR in the frontline setting, their QOL improves. During continued ibrutinib therapy, the improvement in QOL is sustained, and there is no notable reduction in QOL over time. The results of this QOL analysis justify the use of frontline ibrutinib in previously untreated younger CLL patients, given the improvement in PFS and OS with IR over FCR seen in E1912.