ECHO
Trial question
What is the effect of a combination of acalabrutinib with bendamustine/rituximab in patients with untreated mantle cell carcinoma?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
29.0% female
71.0% male
N = 598
598 patients (175 female, 423 male).
Inclusion criteria: adult patients, aged ≥ 65 years, with previously untreated mantle cell carcinoma.
Key exclusion criteria: history of previous malignancy; planning stem cell transplantation; evidence of CNS involvement; significant CVD; concurrent anticoagulation with warfarin or equivalent VKAs.
Interventions
N=299 acalabrutinib plus bendamustine/rituximab (acalabrutinib 100 mg BID plus 6 cycles of bendamustine 90 mg/m² once daily on days 1 and 2 and rituximab 375 mg/m² on day 1, followed by rituximab maintenance in responding patients for 2 years).
N=299 placebo plus bendamustine/rituximab (matching placebo plus 6 cycles of bendamustine 90 mg/m² once daily on days 1 and 2 and rituximab 375 mg/m² on day 1, followed by rituximab maintenance in responding patients for 2 years).
Primary outcome
Median progression-free survival
66.4 months
49.6 months
66.4 months
49.8 months
33.2 months
16.6 months
0.0 months
Acalabrutinib plus
bendamustine/rituximab
Placebo plus
bendamustine/rituximab
Significant
increase ▲
Significant increase in median progression-free survival (66.4 months vs. 49.6 months; HR 1.37, 95% CI 1.06 to 1.75).
Secondary outcomes
No significant difference in overall survival (67.6% vs. 64.5%; HR 1.16, 95% CI 0.88 to 1.54).
Safety outcomes
No significant differences in adverse events, ≥ 3 grade adverse events.
Conclusion
In adult patients, aged ≥ 65 years, with previously untreated mantle cell carcinoma, acalabrutinib plus bendamustine/rituximab was superior to placebo plus bendamustine/rituximab with respect to median progression-free survival.
Reference
Michael Wang, David Salek, David Belada et al. Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma. J Clin Oncol. 2025 May 1:JCO2500690. Online ahead of print.
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