MYC ALTERATIONS IN HIV‐ASSOCIATED B CELL LYMPHOMAS: RESULTS OF “EUROMYC” STUDY (A EUROPEAN RETROSPECTIVE STUDY)

Abstract

Introduction: HIV negative patients (pts) with B cell lymphoma (Ly) carrying MYC rearrangements and BCL2+/-BCL6 translocations [double hit (DHL) or triple hit Ly (THL)] have shown a dismal prognosis when treated with standard chemotherapy. Data about the prognosis of “single hit” Ly, (SHL) are more controverse. In HIV-associated B cell lymphomas (HIV+Ly), scanty data are available on the prevalence and prognostic impact of MYC rearrangements. Methods: This is a retrospective study conducted in 11 European centers with the aim to evaluate the clinical and prognostic impact of MYC rearrangement, evaluated by FISH analysis, in HIV+Ly. We compared HIV+ Ly [diffuse large B cell Ly (DLBCL), B cell Ly unclassifiable, with features intermediate between DLBCL and Burkitt (BCLU), and High grade B cell Ly (HGBL)] with (MYC+) and without (MYC-) MYC rearrangements, treated with standard (R-CHOP or CHOP like) or intensive therapy (iCT) that is, CODOX-IVAC, Carmen trial, GMALL. Results: A total of 161 consecutive pts were enrolled: 49 (30%) were MYC+ and 112 (70%) MYC-. MYC+ pts had higher involvement of central nervous system (CNS) at presentation, higher ki67%, more frequent histology other than DLBCL, translocation of BCL2 and germinal center B phenotype. MYC+ pts received more frequently iCT (45% vs. 20%, p = 0.002). With a median follow-up of 57 months, there were no significant differences in overall survival (OS) and progression-free survival (PFS) between MYC+ and MYC- pts (5 years (y) OS and PFS 55% and 47% in MYC+ and 59% and 53% in MYC- pts). DHL/THL were 10 (13 MYC+ pts did not have data on BCL2/BCL6): compared to 26 SHL they had similar clinical characteristics, but worse outcome with 5y PFS (30% vs. 60%, p = 0.02) and 5y OS (50% vs. 67%, p = 0.07). In univariate analysis IPI≥3, ECOG≥ 2, increased LDH and ki67 < 90% were related to worse OS and PFS while BCL2 translocation with shorter PFS. In multivariate analysis ECOG≥2, elevated LDH and ki67 < 90% maintained their negative impact. In MYC+ pts, iCT was related to better PFS compared to standard therapy (5 y PFS 62% and 35%, p = 0.04) and to a trend of better OS (5 y OS 61% and 52%, p = 0.25) (Figure 1). No pts treated with iCT died from toxicity. Keyword: aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract M. Spina Honoraria: GILEAD, Servier, Novartis, Incyte, BeiGene, Istituto Gentili Research funding: MENARINI L. Arcaini Consultant or advisory role Roche, Janssen-Cilag, Verastem, Incyte, EUSA Pharma, Celgene/Bristol Myers Squibb, Kite/Gilead, ADC Therapeutics Research funding: Gilead Sciences Other remuneration: Speakers’ Bureau: EUSA Pharma, Novartis D. Dalu Educational grants: Roche, Gentili, Lilly and Eisai Other remuneration: Gentili, Daikii Sanchio A. Tucci Consultant or advisory role Gentili, Sanofi, Jannsen Honoraria: Kiowa Kyrin, Takeda