Zanubrutinib Associated With Better Quality of Life Vs Bendamustine/Rituximab in CLL/SLL


Investigators have identified that zanubrutinib may improve the subpar health-related quality of life for patients with treatment-naïve chronic lymphocytic leukemia or small lymphocytic lymphoma.

Paolo Ghia, MD, PhD

Paolo Ghia, MD, PhD

An assessment of patient-reported outcomes from the phase 3 SEQUOIA trial (NCT03336333) showed that patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) receiving zanubrutinib (Brukinsa) experienced improved health-related quality-of-life (HRQOL) outcomes compared with patients receiving bendamustine (Bendeka) plus rituximab (Rituxan), according to data presented at the 2022 EHA Congress.1

Findings showed that patients who received zanubrutinib displayed improvements in HRQOL at both weeks 12 and 24. At week 12, patients who received zanubrutinib saw a mean change from baseline in global health status (GHS) of 2.9 (standard error [SE], 1.62; 95% CI, -0.2 to 6.1), compared with 2.2 (SE, 1.73; 95% CI, -1.2 to 5.6) for patients who received bendamustine plus rituximab. Additionally, at week 12, the mean change in physical function was 1.9 (SE, 1.19; 95% CI, -0.5 to 4.2) with zanubrutinib and 0.9 (SE, 1.26; 95% CI, -1.6 to 3.4) with bendamustine/rituximab, and the mean change in role function was 1.7 (SE, 2.00; 95% CI, -2.3 to 5.6) with zanubrutinib vs -2.8 (SE, 2.13; 95% CI, -6.9 to 1.4) with bendamustine/rituximab.

The week 24 mean change in GHS was 4.8 (SE, 1.64; 95% CI 1.6-8.0) with zanubrutinib and -0.2 (SE, 1.74; -3.6 to 3.3) with bendamustine/rituximab. The mean change in physical function was 3.5 (SE, 1.20; 1.1-5.9) with zanubrutinib and -0.3 (SE, 1.27; 95% CI, -2.8 to 2.2) with bendamustine/rituximab, and the mean change in role function was 2.1 (SE, 2.02; 95% CI, -1.9, 6.1) with zanubrutinib and -2.7 (SE, 2.14; 95% CI, -6.9 to 1.5) with bendamustine/rituximab.

“Greater improvements were observed in GHS, physical function, and role function and in symptoms of fatigue, diarrhea, and nausea/vomiting in treatment-naïve patients who received zanubrutinib compared with patients who received bendamustine plus rituximab; while the 2 arms experienced similar improvements in pain,” lead study author, Paolo Ghia, MD, PhD, deputy director, Division of Experimental Oncology, group leader, B-cell Neoplasia, unit head, Strategic Research Program on CLL, and full professor in Medical Oncology at the Università Vita Salute San Raffaele, wrote in the poster presentation.

The subpar HRQOL for patients with treatment-naïve CLL and SLL compared with the general population remains an unmet need in this space. In addition to treatment-related adverse effects, patients also suffer from chronic fatigue, pain, fever, frequent infections, night sweats, swollen lymph nodes, and enlarged spleen and liver.

BTK inhibitors, including zanubrutinib, have been shown to improve progression-free survival (PFS) and overall survival (OS) in patients. Moreover, zanubrutinib has been designed to result in less off-target effects and is now recommended as the preferred first- and subsequent-line therapy in CLL and SLL.

The open-label, randomized SEQUOIA trial, evaluated the efficacy of zanubrutinib vs bendamustine and rituximab in patients with previously untreated CLL and SLL. An interim analysis of the study showed that PFS at a median follow up of 26.2 months was significantly prolonged in patients who received the BTK inhibitor therapy vs bendamustine/rituximab. Here, HRQOL was evaluated through patient-reported outcomes from baseline through week 24.

Patients were allowed to enroll if they did not have any previous CLL or SLL treatment. Moreover, patients were required have a confirmed diagnosis of CD20-positive CLL or SLL, and ECOG performance score of 2 or less.

Once enrolled, patients were randomized 1:1 to receive either 160 mg of oral zanubrutinib twice a day, or 90 mg/m2 or intravenous bendamustine on the first 2 days of cycles 1 through 6, plus 375 mg/m2 of rituximab in cycle 1, followed by 500 mg/m2 in cycles 2 to 6. Treatment lasted until progression or unacceptable toxicity occurred in patients. Additionally, each cycle of treatment lasted 28 days.

HRQOL outcomes were assessed via patient-reported outcomes that were collected utilizing the European Organization for Research and Treatment of Cancer QLQ-C30. Patient-reported outcomes were assessed for GHS, physical function, role function, and symptoms of fatigue, pain, diarrhea, nausea, and vomiting, which were then measured utilizing a linear mixed-effects model for repeated measurements. This measurement assessed key changes from baseline in each respective arms between weeks 12 and 24.

Overall, baseline demographics and disease characteristics observed were similar between the zanubrutinib and bendamustine/rituximab arms. Patient-related outcomes were available for 92.9% of patients in the zanubrutinib arm (n = 224/241) and 84.9% of patients in the bendamustine plus rituximab arm (n = 202/238). The median age of patients across both arms was 70 years old. The majority of patients were White (89.1%) and male (62.2%). The majority of patients had an ECOG score of 1 (48.6%) and 0 (44.1%).

Additional data at week 24 showed that zanubrutinib achieved mean changes in fatigue (-7.8 [SE, 1.80; 95% CI, -11.3 to -4.2]); nausea/vomiting (-2.3 [SE, 1.06; 95% CI, -4.4 to -0.2]); and diarrhea (-1.4 [SE, 1.52; 95% CI, -4.4 to 1.6]). Those mean changes with bendamustine/rituximab were -3.3 (SE, 1.90; 95% CI, -7.0 to 0.4), 1.9 (SE, 1.12; 95% CI, -0.3 to 4.1), and 4.8 (SE, 1.61; 95% CI 1.7 to 8.0), respectively. Notably, the effects on pain were similar between zanubrutinib and bendamustine/rituximab, with mean changes of 0.7 (SE, 1.88; 95% CI, -3.0 to 4.4) and 0.3 (SE, 1.99; 95% CI, -3.6 to 4.2), respectively.

“For future analyses, examining the interaction between the patient-reported outcomes end points and broader safety assessments may be warranted,” Ghia said. “With improved selectivity and less off-target effects, zanubrutinib may improve HRQOL outcomes in treatment of patients with CLL and SLL.”


  1. Ghia P, Barnes G, Yang K, et al. Patient-reported outcomes from a phase 3 randomized study of zanubrutinib vs bendamustine plus rituximab (BR) in patients with treatment-naive (TN) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at: 2022 EHA Congress; June 9-17, 2022; Vienna, Austria. Abstract P662

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