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- Title
C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional "hits" and outcomes with subsequent therapy.
- Authors
Epperla, Narendranath; Maddocks, Kami J.; Salhab, Mohammed; Chavez, Julio C.; Reddy, Nishitha; Karmali, Reem; Umyarova, Elvira; Bachanova, Veronika; Costa, Cristiana; Glenn, Martha; Calzada, Oscar; Xavier, Ana C.; Zhou, Zheng; Hossain, Nasheed M.; Hernandez‐Ilizaliturri, Francisco J.; Al‐Mansour, Zeina; Barta, Stefan K.; Chhabra, Saurabh; Lansigan, Frederick; Mehta, Amitkumar
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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. © 2017 American Cancer Society.
- Subjects
DIFFUSE large B-cell lymphomas; MYC oncogenes; CANCER immunotherapy; CANCER chemotherapy; SURVIVAL analysis (Biometry); HEMATOPOIETIC stem cells; THERAPEUTICS; ANTINEOPLASTIC agents; B cell lymphoma; CHROMOSOME abnormalities; COMPARATIVE studies; DRUG resistance in cancer cells; HEMATOPOIETIC stem cell transplantation; RESEARCH methodology; MEDICAL cooperation; ONCOGENES; RESEARCH; DISEASE relapse; EVALUATION research; TREATMENT effectiveness; RETROSPECTIVE studies; SALVAGE therapy; TUMOR treatment
- Publication
Cancer (0008543X), 2017, Vol 123, Issue 22, p4411
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.30895