Lymphome diffus à grandes cellules B
Rituximab + cyclophosphamide+doxorubucin+vincristine+prednisone vs Acalabrutinib + Rituximab + cyclophosphamide+doxorubucin+vincristine+prednisone
Assessing the efficacy of acalabrutinib-R-CHOP in DLBCL harboring MYD88 L265P and/or CD79A/B mutations (cohort A)
Assessing the activity of treatment escalation to acalabrutinib-R-CHOP followed by acalabrutinib monotherapy in DLBCL patients who are double positive: PET/CT positive (Deauville score 4) and no molecular response (<2log10 fold reduction) after two courses of R-CHOP (cohort B)
Exploring the feasibility of treatment de-escalation to 4 total R-CHOP courses plus two infusions of single agent rituximab in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two cycles of R-CHOP, which further improve to Deauville score 1-2 and absence of ctDNA after two additional RCHOP courses (cohort C).
Exploring clinical implications of having a negative PET/CT (Deauville score 1-3) but no molecular response (<2log10 reduction of ctDNA) vs a positive PET/CT (Deauville score 4) but molecular response (>2log10 reduction of ctDNA) after two R-CHOP courses (cohort D)
Histologically confirmed, treatment-naïve DLBCL, NOS that fulfill all the following:
CNS lymphoma involvement
Specific diagnostic categories of large B-cell lymphoma such as high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, primary central nervous system lymphoma, T-cell/histiocyte-rich large Bcell lymphoma, intravascular large B-cell lymphoma, plasmablastic lymphoma, lymphomatoid granulomatosis, primary effusion lymphoma etc.
Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon), ‘dual’ antiplatelet therapy (DAPT), such as aspirin and clopidogrel. However, use of therapeutic low
molecule weight heparin, direct oral anticoagulants, or low dose antiplatelet agents is allowed.
Concomitant treatment to Acalabrutinib with strong or moderate CYP3A inducers or inhibitors and co-administration with proton pump inhibitors (PPIs).