Lymphomas With MYC-Translocation Other Than Burkitt’s Have An Aggressive Presentation and Poor Response To Immunochemotherapy: Study Of 34 Cases

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.