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ALPINE, SEQUOIA Findings: Zanubrutinib Offers Improved HRQOL in CLL/SLL


Abstracts presented at the 2022 European Hematology Association Congress demonstrate superior health-related quality of life (HRQOL) outcomes among patients with chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) taking zanubrutinib.

Abstracts presented at the 2022 European Hematology Association (EHA) Congress demonstrate superior health-related quality of life (HRQOL) outcomes among patients with chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) taking zanubrutinib.

An interim analysis of the phase 3 randomized SEQUOIA trial aimed to report HRQOL outcomes among patients with treatment-naïve CLL/SLL.1 The patient-reported outcomes were assessed using HRQOL questionnaires completed at baseline, each 12 weeks for 96 weeks, and then every 24 weeks until disease progression, study withdrawal, or death. The end points included global health status (GHS), physical and role functioning, and symptoms of pain, fatigue, diarrhea, and nausea/vomiting. Investigators compared these outcomes between patients taking zanubrutinib (n = 241) and those receiving bendamustine plus rituximab (BR) (n = 238).

Using the QLQ-C30 scale, a quality-of-life questionnaire for patients with cancer, the patients receiving zanubrutinib reported greater improvements in HRQOL than the patients receiving BR at weeks 12 and 24, though the difference between the groups was only significant at the 24-week mark (zanubrutinib ­– BR difference in GHS score improvement, 12 weeks: 0.7; 95% CI, ­–3.3 to 4.7; P = .73; 24 weeks: 4.9; 0.9-9.0; P = .017). The zanubrutinib group also had significantly better physical and role functioning score improvements and decreases in the measured symptoms by week 24.

Using the EuroQol-5 Dimension visual analog scale (EQ-5D-5L VAS), however, the improvements seen in health status between the zanubrutinib and BR groups were comparable at weeks 12 (4.3 vs 3.5, respectively) and 24 (4.5 vs 4.9).

In an interview with The American Journal of Managed Care®, coauthor Mazyar Shadman, MD, MPH, said that these data “add to the quality of the conversation that a physician and a patient have before selecting any specific therapy, in this case zanubrutinib.”

Another abstract presented results from an interim analysis of the ALPINE trial comparing zanubrutinib and ibrutinib in patients with relapsed/refractory (RR) CLL/SLL.2 This analysis used the same questionnaires as the SEQUOIA analysis to assess the same HRQOL outcomes in the intent-to-treat population (zanubrutinib: n = 327; ibrutinib: n = 325). Responses were collected at cycles 7 and 13, corresponding to 6 and 12 months of treatment, respectively.

Investigators found greater improvement with zanubrutinib vs ibrutinib at cycle 7 (mean [SD] change in EQ-5D-5L VAS from baseline, 8.4 [18.2] vs 4.0 [16.6]) and at cycle 13 (6.8 [18.8] vs 5.2 [17.5]). They also detected differences in favor of zanubrutinib on the QLQ-C30 measures of GHS, physical functioning, and fatigue at cycle 7 and diarrhea at cycle 13. The mean difference in GHS at cycle 7 between the zanubrutinib and ibrutinib groups was 3.45 (95% CI, 0.3-6.6; P = .0322).

“In the ALPINE trial, patients with RR CLL/SLL who received zanubrutinib monotherapy reported improvements in key HRQOL end points compared with patients who received ibrutinib monotherapy,” the abstract authors concluded.

An additional abstract presented at EHA2022 aimed to describe the evolving treatment landscape of CLL in Australia, given the approval of novel Bruton tyrosine kinase (BTK) inhibitors including zanubrutinib.3 Investigators retrieved information from a data set capturing all publicly funded prescription treatments in Australia by selecting data on CLL treatment between January 1, 2011, and July 31, 2021.

In addition to identifying the most common comedications among the 803 patients with CLL, the researchers also noted trends in adoption of newly approved therapies for CLL. Use of BTK inhibitors increased from 0% to 26% in the first line and from 0% to 58% for R/R CLL between 2011 and 2021. Concurrently, use of fludarabine-cyclophosphamide-rituximab in the first line decreased from 78% in 2010 to 11% in 2021.

Another trend identified by the investigators was a drop in CD20-directed monotherapy for R/R disease from 60% to 17% over the study period.

“CLL treatment patterns have significantly changed in Australia since the introduction of the BTK [inhibitors],” the authors summarized.


1. Ghia P, Barnes G, Yang K, et al. Patient-reported outcomes from a phase 3 randomized study of zanubrutinib versus bendamustine plus rituximab (BR) in patients with treatment-naïve (TN) CLL/SLL. HemaSphere. 2022;6(suppl 3):P662.

2. Hillmen P, Brown J, Lamanna N, et al. Health-related quality of life outcomes associated with zanubrutinib vs ibrutinib monotherapy in patients with relapsed/refractory (RR) CLL/SLL: results from the randomized phase 3 ALPINE trial. HemaSphere. 2022;6(suppl 3):P663.

3. Tam C, Zhao FL, Gauba R, Yang K, Azmi S, Li SC. Population-wide patterns of care in chronic lymphocytic leukemia in Australia: an analysis of the Pharmaceutical Benefits Scheme dataset. HemaSphere. 2022;6(suppl 3):P661.

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