MYC⁺ Diffuse Large B Cell Lymphomas (DLBCL) Treated in Randomized Prospective Salvage Therapy, RICE or RDHAP Followed by BEAM Plus Autologous Stem Cell Transplantation (ASCT). A BioCORAL Report

. Approximately 5% to 10% of DLBCLs harbor a MYC/8q24 oncogene rearrangement. We determined the prognostic significance of MYC⁺ DLBCL in a selected population of patients with relapsed/refractory DLBCL included in the CORAL and prospectively treated by RICE or RDHAP followed by BEAM and ASCT¹ . METHODS. Among the 396 patients included, 150 patients were analysed with break-apart FISH probes for MYC/8q24, BCL2/18q21, and BCL6/3q27. Correlations with clinical characteristics at diagnosis and at relapse, immunohistochemistry (IHC) for CD10, BCL6, MUM1, FOXP1, and BCL2 expression, cell of origin determined according to different IHC algorithms^2-5 and by transcriptomic analysis, response to treatment and survivals were analysed considering presence or absence of MYC rearrangement. RESULTS. Twenty-four (16%) cases exhibited a MYC rearrangement, associated in 87.5% (n=21) of the cases with a BCL2/18q21 rearrangement (n=16), with a BCL6/3q27 rearrangement (n=4), and with both BCL2/18q21 and BCL6/3q27 rearrangements (n=4). Among the matched cases analysed (n=57), biological characteristics including tumor immunophenotype and breakpoints occurrence, were identical between primary and secondary biopsies. Presence of MYC⁺ rearrangement was significantly associated with CD10 expression (p= 0.0067) and a GC phenotype, based either on Hans algorithm (p<10⁴ ) or on Alizadeh GC signature (p=0.0015). Patients with MYC⁺ DLBCL presented significantly with more advanced aaIPI (p =.03). Sixty-three percent of them presented a time to relapse < 12 months, compared to 51% in patients with MYC⁻ DLBCL (p=0.2925). Before HDT+ASCT, CR and ORR (PR+CR) were observed in 56% and 63% in patients with MYC⁺ DLBCL, compared to 75% and 87% in patients with MYC⁻ DLBCL (p=0.3442). Outcome of patients with MYC⁺ DLBCL was significantly worse than MYC⁻ DLBCL, with a 4-y PFS at 22% vs 45% (p =.0105) and a 4-y OS at 33% vs 62% (p =.0192). Type of treatment, RDHAP or RICE did not have any impact on survival with a 4-y PFS at 23% vs 22% (p=NS) and a 4-y OS at 44% vs 28% (p=NS), respectively. No difference of outcome was observed between patients with simple hit and with complex hits MYC⁺ DLBCL. CONCLUSION. MYC rearrangement is an early event in DLBCL and is significantly associated with a GC phenotype. Patients with MYC⁺ DLBCL presented with a more advanced disease, and have a significant inferior prognosis than patients with MYC⁻ DLBCLs. Their outcome seems not influenced by the proposed salvage therapy.

No relevant conflicts of interest to declare.