17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Abstract

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable lymphoma. Rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP) is the standard first-line regimen with cure rates nearing 60%. Over the last years many efforts have been made aiming at improving outcomes of first line therapy but none has resulted in improved overall survival over R-CHOP. Recently, genetic subtypes of DLBCL that go beyond the cell-of-origin and have distinct biology, clinical characteristics and different likelihood of response to specific therapies have been identified. One of these entities is represented by the MCD subtype harboring either the MYD88 L265P mutation, the CD79A/B mutation, or both. MCD has a dismal outcome when treated with R-CHOP but is sensitive to BTK inhibition. In addition to the genetic definition of specific subtypes, the possibility to use circulating tumour DNA (ctDNA) response assessment together with PET-response may establishe a new strategy for treatment decisions in patients with DLBCL. Methods: SAKK 38/19 (NCT04604067) is an ongoing exploratory multicohort phase II trial in patients (pts) with previously untreated DLBCL not otherwise specified (NOS). Adult pts with CD20-positive DLBCL NOS, ECOG performance status 0–2, candidates for 6 cycles of R-CHOP are eligible. At baseline, a liquid biopsy is perfomed and pts with MCD subtype are treated with the combination of R-CHOP plus acalabrutinib for 6 cycles (cohort A). Non-MCD pts receive 2 cycles of R-CHOP and based on the combined PET and ctDNA response assessment after cycle 2 they are allocated to one of three different cohorts: R-CHOP for 4 additional cycles in combination with acalabrutinib followed by 2 months of acalabrutinib single-agent (cohort B); 2 additional cycles of R-CHOP and 2 administrations of single-agent rituximab (cohort C); 4 additional cycles of R-CHOP (cohort D). Co-primary endpoints of the trial are: Progression free survival (PFS) (in Cohorts A, C and D) and complete remission (CR) rate (in Cohort B) Secondary endpoints: Adverse events in the cohorts treated with acalabrutinib-R-CHOP; overall survival; PFS in cohort B; CR rate in cohorts A, C and D; overall response rate; duration of response. The research was funded by: -Astra Zeneca -Hubacher Fund Keywords: aggressive B-cell non-Hodgkin lymphoma, liquid biopsy, ongoing trials Conflicts of interests pertinent to the abstract A. Stathis Honoraria: Eli Lilly, Bayer, Roche, Novartis, Janssen Oncology, AstraZeneca Research funding: ADC Therapeutics, Pfizer, Roche, Novartis, Bayer, Eli Lilly, MEI Pharma, Cellestia, Debiopharm Group, Merck/MSD, Abbvie, Amgen, AstraZeneca, Incyte, Loxo, and Philogen F. Hitz Consultant or advisory role Abbvie, Takeda and Roche G. Gritti Consultant or advisory role Roche, Takeda, Kite-Gilead, Ideogen, Genmab Educational grants: Janssen, Beigene, Sandoz Other remuneration: Clinigen, Ideogen, Beigene, Incyte, Novartis T. Zenz Honoraria: Roche, Abbvie, AZD, Beigene, Janssen, Gilead, Novartis