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, Jaglal Michael V, Evens Andrew M, Flowers Christopher R, Cohen Jonathon B, Fenske Timothy S, Hamadani Mehdi, Costa Luciano J
Department of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Department of Hematology, Ohio State University, Columbus, Ohio.
Cancer. 2017 Nov 15;123(22):4411-4418. doi: 10.1002/cncr.30895. Epub 2017 Jul 27.
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.
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.
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.
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.
MYC原癌基因、碱性螺旋-环-螺旋（MYC）易位（伴有或不伴有涉及B细胞淋巴瘤2 [BCL2]或BCL6基因的其他重排）对原发性治疗失败的弥漫性大B细胞淋巴瘤（DLBCL）患者挽救治疗反应及生存的影响尚不明确。
这是一项多中心回顾性研究，旨在探讨MYC、BCL2和BCL6重排在完成初始化疗免疫治疗后6个月内未达到完全缓解或复发的DLBCL患者中的影响。
作者研究了MYC阴性（n = 120）、MYC阳性单打击（SH）（n = 20）和MYC阳性双打击/三打击（DH/TH）（n = 35）队列中患者对挽救治疗的反应、造血细胞移植（HCT）的接受情况及生存结局。这3个队列对首次挽救治疗的总体反应率（分别为51%、50%和54%）及接受HCT的比例（分别为52%、40%和43%）相当。MYC阴性队列的2年总生存率为29.9%，MYC阳性SH队列的为0%，MYC阳性DH/TH队列的为9.9%（P <.001），SH队列和DH/TH队列之间未观察到差异（P =.8）。校正协变量后，MYC阳性SH DLBCL患者（风险比，1.70；95%置信区间，0.98 - 2.96；P =.06）和MYC阳性DH/TH DLBCL患者（风险比，2.22；95%置信区间，1.41 - 3.50；P =.001）的死亡风险仍然较高。对于接受自体HCT的患者，MYC阴性队列的2年总生存率为55.4%，MYC阳性SH队列的为0%，MYC阳性DH/TH队列的为19.4%（P <.001）。所有4例接受异基因HCT的MYC阳性患者均在4个月内复发。
原发性治疗失败的MYC阳性DLBCL患者与MYC阴性患者相比，对挽救治疗的反应率相似，但无论是否有其他“打击”及接受HCT，其生存情况都很差，这代表了一种未满足的医疗需求。《癌症》2017年；123:4411 - 8。©2017美国癌症协会。
