ABCL-181 Germinal Center Double Hit Diffuse Large B-Cell Lymphoma Refractory to Chemoimmunotherapy: A Case Report

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2023-09, Vol.23, p.S423-S423
• Main Authors: Castillo, Sandra Liliana Valencia, Shally, Marcellini Antonio, Ana, Torres Tienza, Angel, Osorio Manyari Miguel, Marta, Mosquera Tapia, Pablo, Jiménez Montero, Aranzazú, García Mateo, Pilar, Galán Álvarez, Carmen, Olivier Cornacchia, Antonio, Queizán Hernández Jose
• Format: Article
• Language: English
• Subjects: CAR-T; chimeric antigen receptor T cells; diffuse large B cell lymphoma; DLBCL; double-hit lymphoma; germinal center B cell; refractory
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/S2152-2650(23)01301-0

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL). Double-hit lymphoma is a colloquial term for high-grade B cell lymphoma with MYC and BCL2and/or BCL6 rearrangements. A lymphoma with DLBCL morphology may be subclassified into germinal center B cell (GCB) DLBCL and activated B cell (ABC) DLBCL. The gold standard treatment includes R-CHOP. R-CHOP cures approximately 60% of patients with DLBCL; however, 30-40% relapse and 10 percent are refractory to treatment. Approximately 50% of patients with relapsed or refractory DLBCL respond to second-line chemotherapy; however, they have a poor prognosis. A 58-year-old male diagnosed with GBC DLBCL subtype with c-MYC and BCL2 rearrangements (Ann Arbor IV-b stage). He was initially treated with two cycles of R-CHOP and achieved a dissociated metabolic response, according to PET. A second line of treatment included two cycles of R-EPOCH. After three cycles, PET showed metabolic progression. We escalated treatment to 2 cycles to R-ESHAP. PET and clinical evaluation showed a partial metabolic response with the persistence of lymphoproliferative disease. CAR-T (chimeric antigen receptor T) cell therapy was initiated. After CAR-T therapy, PET showed a good partial response (Deauville score (DS) 4). Two months later, a right infraclavicular subcutaneous mass indicated progression of the GCB DLBCL (DS 5). The patient was enrolled in a clinical trial comparing brentuximab, vedotin, or placebo in combination with lenalidomide and rituximab (ECHELON-3). After two cycles, the pectoral mass increased as accompanied by the appearance of 2 adjacent lesions. A new PET showed GCB DLBCL criteria with DS 5. The patient was included in a double-blind trial as a fifth line of treatment. He received R-Pola-Benda. After two cycles, PET showed progressive disease (DS5). The patient was included in a new phase 1 clinical trial (CD20/CD47). After two cycles, examining the patient showed evidence of progression (DS5). Currently, the patient is waiting for a seventh line of treatment with epcoritamab. Treatment of advanced-stage DLBCL with curative intent using rituximab-based chemotherapy is associated with long-term survival in more than two-thirds of patients. We described a case of double hit GBC DLBCL refractory to chemoimmunotherapy and CAR-T therapies.