Page 145 - Haematologica May 2022

Non-Hodgkin Lymphoma
Dose-adjusted EPOCH and rituximab for the treatment of double expressor and double-hit diffuse large B-cell lymphoma: impact of TP53 mutations on clinical outcome
Anna Dodero,1* Anna Guidetti,1* Fabrizio Marino,2 Alessandra Tucci,3 Francesco Barretta,4 Alessandro Re,3 Monica Balzarotti,5 Cristiana Carniti Chiara Monfrini,1 Annalisa Chiappella,1 Antonello Cabras,6 Fabio Facchetti,7 Martina Pennisi,1 Daoud Rahal,8 Valentina Monti,6 Liliana Devizzi,1
Rosalba Miceli,4 Federica Cocito,9 Lucia Farina,1 Francesca Ricci,5 Giuseppe Rossi,3 Carmelo Carlo-Stella2#and Paolo Corradini1,10#
1Department of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; 2Department of Biomedical Sciences, Humanitas University and Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, Rozzano-Milano; 3Department of Hematology, ASST Spedali Civili di Brescia, Brescia; 4Department of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; 5Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, Rozzano-Milano; 6Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; 7Department of Pathology, ASST Spedali Civili di Brescia, Brescia; 8Department of Pathology, IRCCS Humanitas Research Hospital, Rozzano- Milano; 9Department of Hematology, Ospedale San Gerardo, Monza and 10Chair of Hematology, University of Milan, Milano, Italy
*AD and AG contributed equally as co-first authors. #CC-S and PC contributed equally as co-senior authors.
ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, including one-third of cases overexpressing MYC and BCL2 pro- teins (double expressor lymphoma, DEL) and 5-10% of patients with chromosomal rearrangements of MYC, BCL2 and/or BCL-6 (double/triple-hit lymphomas, DH/TH). TP53 mutations are detected in 20- 25% of DEL. We report the efficacy of dose-adjusted EPOCH and ritux- imab (DA-EPOCH-R) in a series of 122 consecutive patients, including DEL (n=81, 66%), DEL-MYC (n=9, 7%), DEL-BCL2 (n=13, 11%), or high-grade lymphomas (DH/TH) (n=19, 16%). Central nervous system (CNS) prophy- laxis included intravenous methotrexate (n=66), intrathecal chemotherapy (IT) (n=40) or no prophylaxis (n=16). Sixty-seven patients (55%) had high- intermediate or high International Prognostic Index (IPI) and 30 (25%) had high CNS-IPI. The 2-year progression-free survival (PFS) and overall sur- vival (OS) for the entire study population were 74% and 84%, respectively. There was a trend for inferior OS for DH/TH (2-year OS: 66%, P=0.058) as compared to all the others. The outcome was significantly better for the IPI 0-2 versus IPI 3-5 (OS: 98% vs. 72%, P=0.002). DA-EPOCH-R did not over- come the negative prognostic value of TP53 mutations: 2-year OS of 62% versus 88% (P=0.036) were observed for mutated as compared to wild-type cases, respectively. Systemic CNS prophylaxis conferred a better 2-year OS (94%) as compared to IT or no prophylaxis (76% and 65%, respectively; P=0.008). DA-EPOCH-R treatment resulted in a favorable outcome in patients with DEL and DEL with single rearrangement, whereas those with multiple genetic alterations such as DEL-DH/TH and TP53 mutated cases still have an inferior outcome.
Introduction
Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heteroge- neous disease. Historically DLBCL patients have been uniformly treated with R- CHOP chemoimmunotherapy regimen (rituximab, cyclophosphamide, adri-
Ferrata Storti Foundation
Haematologica 2022 Volume 107(5):1153-1162
Correspondence:
ANNA DODERO
anna.dodero@istitutotumori.mi.it
Received: February 26, 2021. Accepted: July 13 2021. Pre-published: July 22, 2021.
https://doi.org/10.3324/haematol.2021.278638 ©2022 Ferrata Storti Foundation
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