DOUBLE‐HIT (DHL) AND TRIPLE‐HIT LYMPHOMAS (THL): REAL LIFE EXPERIENCE OF 46 CONSECUTIVE PATIENTS FROM A SINGLE INSTITUTION IN SPAIN

Abstract

Introduction: Double‐hit (DHL) and triple‐hit lymphomas (THL) have been described in the 2016 revised WHO classification, they represent a new entity called high‐grade B‐cell lymphoma (HGBCL) with rearrangements of MYC and BCL2 and/or BCL6. DHL/THL have been described as clinically aggressive with a high risk of central nervous system (CNS) and extranodal organ involvement and with a worse prognosis when treated with standard R‐CHOP. Patients and Methods: Retrospective study of 46 consecutive patients with HGBCL with DHL/THL, diagnosed from March 2015 to November 2020, in centers of the Catalan Institute of Oncology in Spain. Survival curves were plotted by the Kaplan‐Meier method. Comparison analysis for survival was performed with the log‐rank test. Results: Clinical characteristics at diagnosis are shown in the table. Of note, 98% presented extranodal disease: bone marrow (n = 11), bone (n = 11), kidney/adrenal (n = 10), lung (n = 9), gastrointestinal (n = 8), soft tissue (n = 8), and CNS involvement (n = 2). Three patients did not receive first line treatment (2 due to old age and 1 patient died few days after diagnosis). Among the 43 patients treated, regimens used were: R‐CHOP: 22 (51%) patients (2 of them R‐miniCHOP), DA‐EPOCH‐R: 14 (33%), intensive regimen used in Burkitt lymphoma: 4 (9%), R‐GEMOX: 1 patient, radiotherapy:1 patient, unknown:1. CNS treatment or prophylaxis consisted in highdose intravenous methotrexate in 9 patients, and intrathecal methotrexate in 5. No patient received stem‐cell transplant in first line. Overall response was 67%; complete remission (CR): 23 (53%), partial remission (PR): 6 (14%), progression: 12 (28%) and 2 patients were not evaluable. CR was 45% after R‐CHOP vs 67% with intensive regimens. With a median follow‐up for the alive patients of 41 months, 23 (50%) patients died, 18 (39%) due to progressive lymphoma, 3 due to septic shock, 1 gastric carcinoma and 1 severe bronchiolitis. There were not CNS relapses. Progression‐free survival (PFS) and overall survival (OS) at 3 years of the 46 patients were 42% (95% CI 26‐57) and 47% (95% CI 38‐62), respectively. PFS at 3 years of patients treated with R‐CHOP versus patients treated with intensive regimens was 40% (95% CI 17‐63) versus 51% (95%CI 25‐77), and OS at 3 years was 47% (95%CI 24‐69) versus 56% (95%CI 29‐83), without statistical significant differences. Conclusions: Almost all patients with HGBCL DHL/THL have extranodal involvement at diagnosis and have other factors of poor prognosis as previously described. Survival of the whole series is poor. Nevertheless, although this is a small series, our data suggest that higher therapeutic intensity could improve outcomes, but PFS and OS of patients treated with R‐CHOP are better than in other older retrospective studies. Therefore, a prospective randomized trial is mandatory to clarify the role of intensive treatments in these patients.