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Clinical Trial
. 2025 Mar 1;110(3):715-724.
doi: 10.3324/haematol.2023.284896.

Safety and efficacy of acalabrutinib plus bendamustine and rituximab in patients with treatment-naïve or relapsed/refractory mantle cell lymphoma: phase Ib trial

Tycel Phillips  1 , Michael Wang  2 , Tadeusz Robak  3 , David Gallinson  4 , Don Stevens  5 , Krish Patel  6 , Safaa Ramadan  7 , Chuan-Chuan Wun  8 , Wojciech Jurczak  9 , Stephen D Smith  10
Affiliations
Clinical Trial

Safety and efficacy of acalabrutinib plus bendamustine and rituximab in patients with treatment-naïve or relapsed/refractory mantle cell lymphoma: phase Ib trial

Tycel Phillips et al. Haematologica. .

Abstract

This multicenter, open-label, phase Ib study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naïve (TN) and relapsed or refractory (R/R) mantle cell lymphoma (MCL). Patients received acalabrutinib from cycle 1 until disease progression or treatment discontinuation, bendamustine on days 1 and 2 of each cycle for up to 6 cycles, and rituximab on day 1 of each cycle for 6 cycles, continuing every other cycle from cycle 8 for 12 additional doses (TN cohort). Eighteen patients enrolled in the TN cohort and 20 in the R/R cohort. Median duration of exposure to acalabrutinib was 34.0 and 14.6 months in the TN and R/R cohorts, respectively. No new safety risks were identified, and most adverse events (AE) were grades 1 or 2. Thirteen patients from the TN cohort (72.2%) and 17 patients from the R/R cohort (85.0%) reported grade 3-4 AE, most commonly neutropenia (TN: 38.9%; R/R: 50.0%). AE leading to death were pneumonitis (N=1, TN cohort), COVID-19, and cerebrospinal meningitis (N=1 each, R/R cohort). Overall response was 94.4% and 85.0% in the TN and R/R cohorts, respectively; complete response rates were 77.8% and 70.0%, respectively. After a median follow-up of 47.6 months, median progression-free survival (PFS) and overall survival (OS) were not reached in the TN cohort. After a median follow-up of 20.4 months, median PFS was 28.6 months and OS was not reached in the R/R cohort. Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL.

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Figures

Figure 1.
Figure 1.
Study design. BID: twice daily; IV: intravenously; MCL: mantle cell lymphoma; PO: orally; PR: partial response; R/R: relapsed/refractory; TN: treatment-naïve. aOne cycle was 28 days. bOnly for patients who achieved a response (PR or better). cUntil disease progression or treatment discontinuation for any reason.
Figure 2.
Figure 2.
Investigator-assessed overall response rate by Lugano criteria. Overall response rate (ORR) is defined as achieving complete response (CR) or partial response (PR). a95% exact binomial confidence interval. bIncludes patients without any adequate post-baseline response assessment. CI: Confidence Interval; NE: not estimable; PD: progressive disease; R/R: relapsed/refractory; SD: stable disease; TN: treatment-naïve.
Figure 3.
Figure 3.
Maximum change from baseline in sum of product diameters for each patient cohort. (A) Change in sum of product diameters (SPD) for the treatment-naïve (TN) cohort is shown. (B) Change in SPD for the relapsed/refractory (R/R) cohort is shown. Results were based on best responses. One patient in the TN cohort (patient had progressive disease [PD]) and 2 patients in the R/R cohort did not have post-baseline tumor measurements and were excluded from SPD analysis. CR: complete response; PR: partial response; SD: stable disease.
Figure 4.
Figure 4.
Progression-free survival for each patient cohort. (A) The Kaplan-Meier plot depicts progression-free survival (PFS) for the treatment-naïve (TN) cohort. (B) The Kaplan-Meier plot for PFS for the relapsed/refractory (R/R) cohort is shown. CI: Confidence Interval; NE: not estimable.
Figure 5.
Figure 5.
Overall survival for each patient cohort. (A) The Kaplan-Meier plot depicts overall survival (OS) for the treatment-naïve (TN) cohort. (B) The Kaplan-Meier plot for OS in the relapsed/refractory (R/R) cohort is shown. CI: Confidence Interval; NE: not estimable.
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References

    1. Dreyling M, Campo E, Hermine O, et al. . Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl 4):iv62-iv71. - PubMed
    1. Narkhede M, Goyal G, Shea L, Mehta A, Giri S. Evaluating real-world treatment patterns and outcomes of mantle cell lymphoma. Blood Adv. 2022;6(14):4122-4131. - PMC - PubMed
    1. Jain P, Wang ML. Mantle cell lymphoma in 2022--a comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments. Am J Hematol. 2022;97(5):638-656. - PubMed
    1. Robak T, Huang H, Jin J, et al. . Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015;372(10):944-953. - PubMed
    1. Robak T, Jin J, Pylypenko H, et al. . Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018;19(11):1449-1458. - PubMed

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