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3042 Rituximab Combined with Chemotherapy and Acalabrutinib Prior to Autologous Stem Cell Transplantation in Mantle Cell Lymphoma: The Rectangle Trial

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphomas, Clinical Research, Combination therapy, B Cell lymphoma, Diseases, Therapies, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Diego Villa, MD1, Jean-Francois Larouche, MD2*, Matthew C. Cheung, MD, MSc3, Mary-Margaret Keating, MD4, Katherine Zukotynski, MD5*, Petter Tonseth, MD6*, Samantha Mayo, RN, PhD7*, Robert Laister, PhD8*, David W. Scott, MBChB, PhD9 and John Kuruvilla, MD, FRCPC10

1Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada
2Centre Hospitalier Universitaire de Québec, Hôpital de l’Enfant-Jésus, Quebec City, Canada
3Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
4Queen Elizabeth II (QEII) Health Sciences Centre, Halifax, NS, CAN
5McMaster University, Departments of Radiology and Medicine, Hamilton, Canada
6Department of Functional Imaging, BC Cancer, Vancouver, BC, Canada
7University of Toronto, Lawrence S. Bloomberg Faculty of Nursing, Toronto, Canada
8Princess Margaret Cancer Centre, Toronto, Canada
9BC Cancer, Vancouver, BC, Canada
10Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre - University Health Network, Toronto, Canada


In the European MCL Network Triangle study (Dreyling, ASH 2022) the addition of ibrutinib to frontline rituximab-containing chemotherapy and subsequent maintenance therapy improved failure-free survival in young, fit patients with mantle cell lymphoma (MCL). Ibrutinib was administered with R-CHOP, but not with R-DHAP, during the induction phase.

Continuous, uninterrupted Bruton Tyrosine Kinase (BTK) inhibition could maximize the benefit of front-line therapy given that responses develop over time. Acalabrutinib has less off-target BTK inhibition than ibrutinib. We hypothesize that combining continuous acalabrutinib with R-CHOP may result in a tolerable, outpatient, highly active regimen producing favorable outcomes.


NCT04566887 is a phase II, single-arm, open-label study conducted across 5 academic centres in Canada. Patients ≥ 18 years of age with previously untreated MCL, ECOG performance status 0-2, adequate organ function and considered fit for autologous stem cell transplantation (ASCT) were included. Patients received 6 cycles of R-CHOP at standard doses plus acalabrutinib 100 mg twice per day orally. Responding patients proceeded with ASCT and maintenance rituximab and acalabrutinib for a total of 2 years.

The primary endpoint was the complete response (CR) rate after 6 cycles of induction with centrally reviewed PET/CT using the Lugano Criteria (Cheson, 2014). The total sample size was n=54 and the study completed accrual in May 2023. We present the results of the first 43 patients who have completed response assessment according to local investigators after 6 cycles of induction.


The median age was 62 years (range 38 – 69), 26 (60%) were male, 42 (98%) had performance status 0-1, 33 (78%) Ann Arbor stage IV, 35 (81%) bone marrow involvement, 6 (14%) high risk MIPI, 7 (16%) blastoid/pleomorphic morphology, 11 (26%) Ki67 ≥30%. All patients completed 6 cycles of induction and proceeded to ASCT. The overall response rate was 100%, and 39 (91%) patients achieved a CR. All patients started maintenance acalabrutinib + rituximab, although none have yet completed two years of protocol maintenance therapy.

With a median follow up of 11.8 months (range 3.4 – 25.3) by the reverse Kaplan-Meier method, the 12-month PFS was 94% (95% CI 78.1 – 98.5), shown in Figure 1, and OS 95.5% (95% CI 71.9 – 99.3).

Three subjects have developed PD so far, all with adverse clinical and biological factors:

  • Baseline high-risk MIPI and Ki67 70%; biopsy at relapse TP53 positive by immunohistochemistry (IHC),
  • Baseline intermediate risk MIPI and Ki67 60%; biopsy at relapse with pleomorphic morphology, TP53 positive by IHC, Ki67 100%,
  • Baseline high risk MIPI, Ki67 ≥30%, and blastoid morphology.

Table 1 lists common grade 3-4 adverse events (AE) during induction and maintenance. There were no grade 5 AE. Neutropenia was the most common AE during induction and maintenance. Most infections were respiratory. Cardiovascular toxicity was uncommon.


Acalabrutinib + R-CHOP is associated with a 91% CR rate with low rates of grade 3-4 AE expected for this combination. All patients have proceeded to ASCT and subsequent maintenance therapy. Maintenance therapy in this setting is associated with additional toxicity, particularly cytopenias and infections.

Disclosures: Villa: Roche, AstraZeneca, Abbvie, Janssen, Kite/Gilead, BMS/Celgene, BeiGene, Merck: Consultancy, Honoraria; Roche, AstraZeneca: Research Funding. Keating: Janssen, Roche: Consultancy. Scott: Abbvie, AstraZeneca, Incyte: Consultancy; Janssen and Roche: Research Funding. Kuruvilla: Abbvie, Amgen, Astra Zeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, Roche, Seattle Genetics: Honoraria; Karyopharm: Other: DSMB; Abbvie, BMS, Gilead, Merck, Roche, Seattle Genetics: Consultancy; Roche, Astra Zeneca, Merck: Research Funding.

OffLabel Disclosure: Frontline acalabrutinib in mantle cell lymphoma is currently considered off-label. The study has been approved by Health Canada.

*signifies non-member of ASH