Lymphomas With MYC-Translocation Other Than Burkitt’s Have An Aggressive Presentation and Poor Response To Immunochemotherapy: Study Of 34 Cases
Authors: Navarro Jose-Tomas , Baptista Maria Joao , Martinez-Trillos Alejandra , Tapia Gustavo , Hernandez-Rivas Jose Angel , Garcia Olga , Muñoz-Marmol Anna , Sancho Juan-Manuel , Millá Fuensanta , Feliu Evarist , Mate Jose-Luis , Lopez-Guillermo Armando , Ribera Josep-Maria 
Published: October 2019

Abstract

Introduction
MYC translocations involving chromosome 8q24 can occur in a wide variety of B-cell lymphomas other than Burkitt’s lymphoma (BL), especially diffuse large B-cell lymphoma (DLBCL) and B-cell lymphoma unclassifiable with intermediate features between DLBCL and BL (BCLU). These lymphomas can harbor additional translocations of BCL2 and/or BCL6, that have been referred to as double and triple-hit lymphomas. MYC positive lymphomas other than BL are not well characterized and the standard treatment has to be established.

Aim
The objective was to study the clinic-biological characteristics and prognosis of a series of lymphomas with MYC-translocation other than BL.

Methods
Retrospective study of patients with MYC-translocation other than BL treated in three hospitals of Spain between 2003 and 2012. Cases with diagnosis of BL, Burkitt’s-like lymphoma and any other with MYC-translocation were reviewed and classified according to the WHO 2008 criteria. The status of MYC, BCL2 and BCL6 genes were evaluated in all cases by fluorescent in situ hybridization (FISH) using dual-colour break-apart commercial probes (LSI MYC DC BA, LSI BCL6 DC BA and LSI BCL2 DC BA; Abbot Molecular, Abbot Park, IL, USA) on whole tissue sections of formalin-fixed paraffin-embedded tissue. Main clinical and biological data were collected from the records.

Results
Between 2003 and 2012, 34 patients with a median follow-up of 1.9 years (range 0.7-9.7) were included. Median age was 59.5 years (range 36-83) and 21 (62%) were male. ECOG score at diagnosis was ≥2 in 14 patients (42%), 16 (49%) had ≥2 extranodal sites involved, serum LDH was elevated in 24 out of 32 (75%), Ann Arbor stage III/IV in 24 (73%) and B symptoms were present in 18 (56%). IPI was high or intermediate/high in 19 out of 32 (59%). Eighteen patients (53%) presented with a mass (13 abdominal location). Twenty-four cases were diagnosed with DLBCL and 10 with BCLU. Conventional cytogenetics showed a complex karyotype in the 9 studied cases. MYC rearrangement alone without BCL2 or BCL6 rearrangements was observed in 13 (38%) cases, 15 were double-hit, and 6 triple-hit lymphomas. There were no differences between patients with MYC translocation alone and patients with double or triple-hit, regarding the clinical and biological characteristics. Moreover, there were no clinical and biological differences between patients with DLBCL and those with BCLU. Twenty-one cases were treated with R-CHOP (19 DLBCL and 2 BCLU), and 13 with a specific treatment for BL (Burkimab) (8 BCLU and 5 DLBCL) (P=0.002). Complete response (CR) was achieved in 14 out of 32 (44%) cases (9 out of 21 [45%] treated with R-CHOP and 5 out of 13 [42%] with Burkimab). Two patients died during chemotherapy. Six out of the 9 patients in CR to R-CHOP relapsed, but none of the 5 patients in CR to Burkimab did it. The overall survival (OS) probability and progression free survival (PFS) at 2 years, (95% CI) for the whole series were 32% (14%, 50%) and 21% (6%, 36%) respectively. The two-year OS and PFS probabilities were not significantly different between patients treated with Burkimab and those treated with R-CHOP: 62% (95% CI: 36%, 88%) versus 28% (95% CI: 8%, 48%) for OS (P=0.67); and 46% (95% CI: 19%, 73%) versus 15% (95% CI: 0%, 31%) for PFS (P=0.549), respectively.

Conclusions
Lymphomas with MYC translocation other than BL present aggressive characteristics at diagnosis and have poor response to immunochemotherapy.
Supported in part by grants EC11-041 and RD12/0036/0029 RTICC from Instituto Carlos III, Spain

Disclosures:
Lopez-Guillermo: Roche: Membership on an entity’s Board of Directors or advisory committees.