C-MYC-Positive Relapsed and Refractory, Diffuse Large B-Cell Lymphoma: Impact of Additional "Hits" and Outcomes With Subsequent Therapy

被引：27

作者：

Epperla, Narendranath ^{[1
]}

Maddocks, Kami J. ^{[2
]}

Salhab, Mohammed ^{[3
]}

Chavez, Julio C. ^{[4
]}

Reddy, Nishitha ^{[5
]}

Karmali, Reem ^{[6
]}

Umyarova, Elvira ^{[7
]}

Bachanova, Veronika ^{[8
]}

Costa, Cristiana ^{[9
]}

Glenn, Martha ^{[10
]}

Calzada, Oscar ^{[11
]}

Xavier, Ana C. ^{[12
]}

Zhou, Zheng ^{[3
]}

Hossain, Nasheed M. ^{[13
]}

Hernandez-Ilizaliturri, Francisco J. ^{[14
]}

Al-Mansour, Zeina ^{[15
]}

Barta, Stefan K. ^{[13
]}

Chhabra, Saurabh ^{[1
]}

Lansigan, Frederick ^{[16
]}

Mehta, Amitkumar ^{[12
]}

Jaglal, Michael V. ^{[4
]}

Evans, Andrew ^{[15
]}

Flowers, Christopher R. ^{[11
]}

Cohen, Jonathon B. ^{[11
]}

Fenske, Timothy S. ^{[1
]}

Hamadani, Mehdi ^{[1
]}

Costa, Luciano J. ^{[12
]}

机构：

[1] Med Coll Wisconsin, Dept Hematol Oncol, Milwaukee, WI 53226 USA

[2] Ohio State Univ, Dept Hematol, Columbus, OH 43210 USA

[3] Univ Massachusetts, Mem Med Ctr, Childrens Med Ctr, Worcester, MA 01605 USA

[4] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA

[5] Vanderbilt Univ, Dept Hematol Oncol, 221 Kirkland Hall, Nashville, TN 37235 USA

[6] Rush Univ, Med Ctr, Dept Hematol Oncol & Cell Therapy, Chicago, IL USA

[7] Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA

[8] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplant, Box 736 UMHC, Minneapolis, MN 55455 USA

[9] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA

[10] Univ Utah, Sch Med, Salt Lake City, UT USA

[11] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[12] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA

[13] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[14] Roswell Pk Canc Ctr, Dept Med, Buffalo, NY USA

[15] Tufts Univ, Dept Med, Med Ctr, Sect Hematol & Oncol, Boston, MA 02111 USA

[16] Dartmouth Hitchcock Med Ctr, Dept Hematol Oncol, Lebanon, NH 03766 USA

来源：

CANCER | 2017年 / 123卷 / 22期

基金：

美国国家卫生研究院;

关键词：

diffuse large B-cell lymphoma (DLBCL); hematopoietic cell transplantation (HCT); MYC proto-oncogene; basic helix-loop-helix (MYC); non-Hodgkin lymphoma; POOR-PROGNOSIS; SURVIVAL; EXPRESSION; REARRANGEMENTS; TRANSLOCATION; FAILURE; BCL2;

D O I：

10.1002/cncr.30895

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (c) 2017 American Cancer Society.

引用

页码：4411 / 4418

页数：8

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