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Epperla N , Maddocks KJ , Salhab M , Chavez JC , Reddy N , Karmali R , Umyarova E , Bachanova V , Costa C , Glenn M , Calzada O , Xavier AC , Zhou Z , Hossain NM , Hernandez-Ilizaliturri FJ , Al-Mansour Z , Barta SK , Chhabra S , Lansigan F , Mehta A , Jaglal MV , Evans A , Flowers CR , Cohen JB , Fenske TS , Hamadani M , Costa LJ
C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional "hits" and outcomes with subsequent therapy
Cancer. 2017 Nov 15;123(22) :4411-4418
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Abstract
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 <4 months. CONCLUSIONS: Patients with MYC-positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC-negative counterparts, but their survival is dismal irrespective of additional "hits" and HCT, representing an unmet medical need. Cancer 2017;123:4411-8. (c) 2017 American Cancer Society.
Notes
1097-0142 Epperla, Narendranath ORCID: http://orcid.org/0000-0002-8216-3457 Maddocks, Kami J Salhab, Mohammed Chavez, Julio C Reddy, Nishitha Karmali, Reem Umyarova, Elvira Bachanova, Veronika ORCID: http://orcid.org/0000-0002-9325-432X Costa, Cristiana Glenn, Martha Calzada, Oscar Xavier, Ana C ORCID: http://orcid.org/0000-0002-3659-3798 Zhou, Zheng Hossain, Nasheed M Hernandez-Ilizaliturri, Francisco J Al-Mansour, Zeina Barta, Stefan K Chhabra, Saurabh Lansigan, Frederick Mehta, Amitkumar Jaglal, Michael V Evans, Andrew Flowers, Christopher R ORCID: http://orcid.org/0000-0002-9524-3990 Cohen, Jonathon B Fenske, Timothy S Hamadani, Mehdi Costa, Luciano J Journal Article Multicenter Study Observational Study United States Cancer. 2017 Nov 15;123(22):4411-4418. doi: 10.1002/cncr.30895. Epub 2017 Jul 27.