The phase II SAKK (NCT04604067) trial aims to evaluate a PET/CT and ctDNA-oriented therapy in DLBCL in order to test whether the addition of acalabrutinib to R-CHOP may improve the PFS in DLBCL patients harboring the MYD88 L265P and/or CD79A/B mutations or in patients who have positive PET/CT and no molecular response (<2log10 reduction of ctDNA) after two courses of R-CHOP. Here, MYD88 is linked to diffuse large B-cell lymphoma.