Ibrutinib Can Induce Complete Remissions and Sustained Responses in Refractory Cutaneous or Leg-Type Diffuse Large B-Cell Lymphoma

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.4237-4237
• Main Authors: Bloehdorn, Johannes, Weissinger, Stephanie Ellen, Sindrilaru, Anca, Schoensteiner, Stefan, Peters, Thorsten, Moeller, Peter, Marienfeld, Ralf, Viardot, Andreas
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-117032

Background: Primary cutaneous diffuse large B-cell lymphoma, leg-type (LT-DLBCL) is an extremely aggressive DLBCL subtype typically occurring at lower extremities and with very poor prognosis due to early relapses and refractory (R/R) disease. Previous studies have shown increased BCR dependence in DLBCL being observed in association with the mutation status of BCR associated genes and MYD88. Aim: Primary goal was to assess the clinical course in patients with primary cutaneous DLBCL and to elucidate the potential of alternative treatments with regard to molecular characteristics. Methods: We identified 16 patients with cutaneous DLBCL treated at our center of which 8 patients had typical localization and were histologically confirmed as LT-DLBCL. The other 8 patients showed cutaneous DLBCL at other anatomic sites (DLBCL-OS) and were classified as DLBCL/DLBCL NOS. Three R/R patients received ibrutinib as off-label individual treatment attempt (420 mg daily). We extended the clinical and molecular analysis for the ibrutinib exposed DLBCL by 1 R/R oropharyngeal DLBCL. Specimen from R/R ibrutinib exposed and 3 other patients were analyzed for CD79B, MYD88, CARD11 and BTK mutations by targeted resequencing analysis. PD-1/PD-L1 expression was assessed in 2 cases with relapse after ibrutinib. Treatment was initiated after signed informed consent. Results: The median age at diagnosis was 51 years in DLBCL-OS and 80 years in LT-DLBCL (total range 37-91). Patients received a median of 2 (0-7) treatments and response to last chemotherapy was different for DLBCL-OS (6 complete remissions (CR), 2 R/R) and LT-DLBCL (2CR, 5R/R). One LT-DLBCL patient showed stable disease (SD) without treatment. LT-DLBCL patients showed a significantly shorter median overall survival (OS) (21,5 months vs. not reached, p=0.009). After ibrutinib treatment we observed 1 ongoing CR for 10 months till date for a DLBCL-OS with CD79B p.Y197S and MYD88 L273P mutation and 1 CR for 6 months in a LT-DLBCL being WT for all sequenced genes. However, this patient relapsed with a highly proliferative disease and died shortly after. The 3rd patient with LT-DLBCL had an isolated MYD88 L265P mutation and showed a PR for 1 month. Samples from patients with indolent clinical course showed a MYD88 p.S251N and BTK p.P385S mutation (LT-DLBCL with SD) or were WT for all sequenced genes (2 patients with DLBCL-OS and ongoing CR). The patient with R/R oropharyngeal DLBCL had a MYD88 L265P and CD79B c.587A mutation