Long-Term Data Show QOL Advantage of Zanubrutinib in 3 Cancers

Results from a long-term follow-up of the ASPEN trial of zanubrutinib in Waldenström macroglobulinemia (WM) showed greater improvements in quality of life (QOL) vs ibrutinib, and data from the ALPINE trial showed zanubrutinib’s QOL advantage in relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The posters were presented at the European Hematology Association 2023 Congress, held in Frankfurt, Germany, from June 8-11. The meeting’s agenda this year reflects a focus on incorporating patient-reported outcomes and real-world data in hematology and oncology.

The first abstract contained findings from the long-term follow-up of the phase 3 ASPEN trial (NCT03053440) comparing zanubrutinib and ibrutinib in patients with WM, looking specifically at a cohort of 201 patients with activating mutations in MYD88.¹ Patients in the zanubrutinib (n = 102) and ibrutinib (n = 99) arms were asked to complete 2 health-related QOL (HRQOL) questionnaires at baseline, at every 3 cycles up to cycle 13, and every 6 cycles subsequently.

Baseline characteristics were largely similar between the arms, although the zanubrutinib arm had more patients older than 75 years (33.3% vs 22.2%) and more patients with anemia (65.7% vs 53.5%). Adherence rates were high in both arms, but the ibrutinib arm had more adverse events (AEs) leading to dose holds or reductions, drug discontinuation, or deaths.

By cycle 4, patients receiving ibrutinib were significantly more likely to experience diarrhea and nausea/vomiting than those receiving zanubrutinib. The gap between the arms closed as the cycles went on, with those symptoms staying stable in the zanubrutinib arm and ameliorating in the ibrutinib arm. Other symptoms improved from baseline in both groups but did not differ significantly between the arms.

The zanubrutinib arm had a shorter median time to very good partial response (VGPR), at 8 months vs 17 months, and their combined complete response and VGPR rate was higher (38.2% vs 25.3%; P = .0374). The 31 patients taking zanubrutinib who achieved VGPR by cycle 25 generally had better patient-reported outcomes.

Among just those who achieved VGPR, the zanubrutinib arm had higher physical functioning scores than the ibrutinib arm and lower fatigue scores, both at cycle 7 (difference in physical functioning, 10.42; 95% CI, 0.57-20.28; P = .0387; difference in fatigue, –11.76; 95% CI, ­–22.24 to ­–1.28; P = .0288) and at cycle 25 (physical functioning, 10.45; 95% CI, 0.12-20.79; P = .0476; fatigue, ­–13.53; 95% CI, ­–25.00 to –2.06; P = .0220). The zanubrutinib arm also compared favorably in terms of diarrhea and nausea/vomiting symptoms at cycle 4.

“The improved HRQOL seen with zanubrutinib among patients who achieved VGPR by cycle 25 is consistent with the shorter median time to VGPR in the zanubrutinib arm and suggests that when disease is controlled to a similar extent, patients fare better in overall HRQOL when treated with zanubrutinib vs ibrutinib,” the poster concluded.

The authors noted that these responses support the use of zanubrutinib as an effective Bruton tyrosine kinase inhibitor therapy option in WM.

The second abstract also assessed health-related QOL in zanubrutinib vs ibrutinib, this time using data from the ALPINE study (NCT03734016) of patients with relapsed/refractory CLL or SLL.² It contained data through the August 8, 2022, cutoff for a progression-free survival analysis of zanubrutinib, at which point the participants had a median of 29.6 months follow-up time.

The zanubrutinib (n = 327) and ibrutinib (n = 325) arms were largely similar in composition and had similar symptom scores at baseline. More patients in the ibrutinib arm discontinued therapy because of AEs than in the zanubrutinib arm (22.2% vs 15.4%).

The main analysis focusing on efficacy found that zanubrutinib demonstrated superiority in terms of overall response rate (86.2% vs 75.7%; P = .007) and progression-free survival (HR, 0.65; 95% CI, 0.49-0.86; P = .0024), but the aim of this poster was to assess HRQOL. Like the ASPEN poster, it used validated scales including the EuroQoL EQ-5D 5-level visual analogue scale asking patients to rate their general health today and the global health status, functioning, and symptom scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire.

By cycle 7 (6 months), global health status scores had significantly improved with zanubrutinib vs ibrutinib (difference, 3.00; 95% CI, 0.23-5.77; P = .0338); by the time of cycle 13, 6 months later, the improvement in scores was still in favor of zanubrutinib but no longer significant (1.34; 95% CI, ­–1.37 to 4.06).

At both cycles 7 and 13, the patients receiving zanubrutinib reported clinically meaningful improvements (≥ 5% mean change) from baseline in pain, fatigue, and physical and role functioning, but the between-arm differences were not significant. Mean visual analogue scale scores improved more in the zanubrutinib arm at both cycle 7 (7.92 vs 3.44) and cycle 13 (7.75 vs 3.92).

The authors of the poster noted that both arms had generally good HRQOL at baseline, which could be why the differences between the arms were small and nonsignificant. However, they noted that patient-reported end points continued to improve in the zanubrutinib arm throughout the duration of treatment, suggesting that the Bruton tyrosine kinase inhibitor “positively affected HRQOL and that HRQOL improved over time.”

They hoped that longer-term follow-ups and further analyses linking patient-reported outcomes to clinical end points will shed additional light on the extent to which zanubrutinib improves HRQOL.

References

1. Tedeschi A, Tam CS, Owen RG, et al. Health-related quality of life in patients with Waldenström macroglobulinemia (WM) treated with zanubrutinib vs ibrutinib: results from the phase 3 ASPEN trial long-term follow-up. Poster presented at: European Hematology Association 2023 Congress; June 8-11, 2023; Frankfurt, Germany. Poster P1679.

2. Eichhorst B, Lamanna N, O’Brien SM, et al. Zanubrutinib vs ibrutinib in relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): impact on health-related quality of life (HRQoL). Association 2023 Congress; June 8-11, 2023; Frankfurt, Germany. Poster P640.