C‐MYC–positive relapsed and refractory, diffuse large B‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy

BACKGROUND The impact of MYC proto‐oncogene, basic helix‐loop‐helix (MYC) translocations (with or without additional rearrangements involving the B‐cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC‐negative (n = 120), MYC‐positive single hit (SH) (n = 20), and MYC‐positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2‐year overall survival rate was 29.9% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 9.9% in the MYC‐positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC‐positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98‐2.96; P = .06) and those with MYC‐positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41‐3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2‐year overall survival rate was 55.4% in the MYC‐negative cohort, 0% in the MYC‐positive SH cohort, and 19.4% in the MYC‐positive DH/TH cohort (P < .001). All 4 MYC‐positive patients who underwent allogeneic HCT relapsed in