TY - JOUR
T1 - C-MYC–positive relapsed and refractory, diffuse large B-cell lymphoma
T2 - Impact of additional “hits” and outcomes with subsequent therapy
AU - Epperla, Narendranath
AU - Maddocks, Kami J.
AU - Salhab, Mohammed
AU - Chavez, Julio C.
AU - Reddy, Nishitha
AU - Karmali, Reem
AU - Umyarova, Elvira
AU - Bachanova, Veronika
AU - Costa, Cristiana
AU - Glenn, Martha
AU - Calzada, Oscar
AU - Xavier, Ana C.
AU - Zhou, Zheng
AU - Hossain, Nasheed M.
AU - Hernandez-Ilizaliturri, Francisco J.
AU - Al-Mansour, Zeina
AU - Barta, Stefan K.
AU - Chhabra, Saurabh
AU - Lansigan, Frederick
AU - Mehta, Amitkumar
AU - Jaglal, Michael V.
AU - Evans, Andrew
AU - Flowers, Christopher R.
AU - Cohen, Jonathon B.
AU - Fenske, Timothy S.
AU - Hamadani, Mehdi
AU - Costa, Luciano J.
N1 - Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/11/15
Y1 - 2017/11/15
N2 - 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.
AB - 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.
KW - MYC proto-oncogene
KW - basic helix-loop-helix (MYC)
KW - diffuse large B-cell lymphoma (DLBCL)
KW - hematopoietic cell transplantation (HCT)
KW - non-Hodgkin lymphoma
UR - https://www.scopus.com/pages/publications/85026327949
UR - https://www.scopus.com/pages/publications/85026327949#tab=citedBy
U2 - 10.1002/cncr.30895
DO - 10.1002/cncr.30895
M3 - Article
C2 - 28749548
AN - SCOPUS:85026327949
SN - 0008-543X
VL - 123
SP - 4411
EP - 4418
JO - Cancer
JF - Cancer
IS - 22
ER -
