Efficacy Waldenström’s macroglobulinaemia (WM)

The efficacy of BRUKINSA^®▼ for the treatment of WM was evaluated in a randomised trial:^1,2

• ASPEN was a phase 3, open-label, randomised multicentre trial comparing BRUKINSA with ibrutinib in patients with WM who were Bruton’s tyrosine kinase (BTK) inhibitor naïve^1–4

Results from the ASPEN study demonstrate that BRUKINSA is an effective treatment for WM.² Treatment with BRUKINSA was associated with a trend towards better disease control and greater improvement in quality of life measures versus ibrutinib.²

Very good partial response (VGPR) or complete response (CR)

In the ASPEN study, the primary end point was the proportion of patients in Cohort 1 (MYD88^L265P) who achieved a VGPR or CR, as assessed by an independent review committee (IRC).² The testing for the superiority of the primary endpoint required testing in the relapsed/refractory (R/R) analysis set prior to testing in the intention-to-treat (ITT) analysis set.^1,2

At a median follow up of 19.4 months, 29% (24/83) of patients with R/R disease in the BRUKINSA arm, and 20% (16/81) in the ibrutinib treatment arm achieved VGPR (2-sided p=0.12; Figure 1), therefore the primary endpoint was not significant in the R/R analysis set.² In the ITT analysis set, a higher proportion of patients in the BRUKINSA treatment arm achieved VGPR compared with the ibrutinib arm (28% [29/102] versus 19% [19/99], respectively; 2-sided p=0.09; Figure 1).² This trend was also observed amongst treatment-naïve patients (26% [5/19] versus 17% [3/18] in the BRUKINSA and ibrutinib treatment arms respectively; 2-sided p=0.54). No patients in either arm of Cohort 1 achieved a CR (N=201).² Extended follow-up results at median 44.4 months showed that VGPR rates increased over time and were numerically higher with BRUKINSA than ibrutinib at all time points.⁴ VGPR rates were 36.3% with BRUKINSA and 25.3% with ibrutinib.⁴

Patients assigned to Cohort 2 (MYD88^WT) received BRUKINSA; after a median follow up of 17.9 months, 27% (7/26) of patients had achieved a VGPR.³ After a median follow up of 30 months the VGPR + CR rate was 30.8% with one CR.⁴

Figure 1. ASPEN: Patients with IRC-assessed VGPR in BRUKINSA versus ibrutinib treatment arms.²

Major response rate (MRR)

MRRs were similar between treatment groups.² MRRs overall were 77% (95% CI 68, 85) and 78% (95% CI 68, 86) in the BRUKINSA and ibrutinib treatment arms respectively.² MRRs for treatment-naïve patients were 74% (95% CI 49, 91) and 67% (95% CI 41, 87), and for patients with R/R disease were 78% (95% CI 68, 87) and 80% (95% CI 70, 88) in the BRUKINSA and ibrutinib treatment arms respectively.² MRR was 50% (95% CI 30, 70) for patients in Cohort 2.^1,3

After extended follow-up (median 44.4 months for Cohort 1 and 42.9 months for Cohort 2), MRRs were 79.8% (95% CI 70.5, 87.2) and 81.4% (95% CI 72.4, 88.4) with BRUKINSA and ibrutinib respectively in Cohort 1, and 65.4% (95% CI 44.3, 82.8) for Cohort 2.⁴

Progression-free survival (PFS)

After a median follow-up of 18 and 18.5 months, 15% of patients treated with BRUKINSA and 16% of patients treated with ibrutinib in Cohort 1 progressed or died, and median PFS was not reached for either arm.² After a median follow-up of 17.9 months, median PFS was not reached in Cohort 2.³

Based on an updated data cut-off at 30 months, the progression free-survival event-free rate by investigator assessment was 84.9% versus 77.6% for BRUKINSA versus ibrutinib respectively, with an estimated overall hazard ratio of 0.734 (95% CI: 0.380, 1.415).¹ After extended follow-up (median 44.4 months for Cohort 1 and 42.9 months for Cohort 2) median PFS was not reached for either treatment arm in Cohort 1 and median PFS was 45.8 in Cohort 2.⁴

Abbreviations: CI, confidence interval.