Rituximab combined with chemotherapy and acalabrutinib prior to autologous stem cell transplantation in mantle cell lymphoma: The Rectangle Trial
Bibliographic record
Abstract
Introduction: In the European MCL Network Triangle study 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 is a second generation BTK inhibitor with less off-target inhibition than ibrutinib. We hypothesize that combining continuous acalabrutinib with R-CHOP may result in a tolerable, outpatient, highly active regimen producing favorable outcomes. Methods: NCT04566887 is a phase II, non-randomized, single-arm 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. The total sample size is n = 54. We present the results of a preplanned interim analysis when the first 24 subjects completed response assessments after 6 cycles of induction. The study would be terminated if <15/24 patients achieved a CR. Results: The median age was 60 years (range 38–69), 16 (67%) were male, 23 (96%) had performance status 0–1, 19 (79%) Ann Arbor stage IV, 19 (79%) bone marrow involvement, 4 (17%) high risk MIPI, 3 (13%) blastoid/pleomorphic morphology, 7 (29%) Ki67 ≥30%. All patients completed 6 cycles of induction and proceeded to ASCT. The overall response rate was 100%, and 19 (79%) patients achieved a CR. 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 adverse events (AE) during the 6 cycles of induction. There were no grade 5 AE. Most infections were respiratory including 1 case with mild COVID-19. Conclusions: Acalabrutinib + R-CHOP is associated with a 79% CR rate with low rates of grade 3–4 AE expected for this combination. The study is ongoing, with expected full accrual by April 2023. The research was funded by: This investigator-initiated trial was funded by AstraZeneca. Keywords: combination therapies, indolent non-Hodgkin lymphoma, molecular targeted therapies Conflicts of interests pertinent to the abstract. D. Villa Consultant or advisory role: AstraZeneca, Janssen, BeiGene, Kite/Gilead, BMS/Celgene, Merck, Abbvie, Roche Honoraria: AstraZeneca, Janssen, BeiGene, Kite/Gilead, BMS/Celgene, Merck, Abbvie, Roche Research funding: AstraZeneca, Roche (research funding to the institution) D. Scott Consultant or advisory role: Abbvie, AstraZeneca, Incyte Research funding: Janssen, Roche Other remuneration: Patents using gene expression to subtype aggressive lymphoma, including one licensed to Veracyte J. Kuruvilla Research funding: AstraZeneca (to the institution)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".