Scott Emma C, Hari Parameswaran, Sharma Manish, Le-Rademacher Jennifer, Huang Jiaxing, Vogl Dan, Abidi Muneer, Beitinjaneh Amer, Fung Henry, Ganguly Siddhartha, Hildebrandt Gerhard, Holmberg Leona, Kalaycio Matt, Kumar Shaji, Kyle Robert, Lazarus Hillard, Lee Cindy, Maziarz Richard T, Meehan Kenneth, Mikhael Joseph, Nishihori Taiga, Ramanathan Muthalagu, Usmani Saad, Tay Jason, Vesole David, Wirk Baldeep, Yared Jean, Savani Bipin N, Gasparetto Cristina, Krishnan Amrita, Mark Tomer, Nieto Yago, D'Souza Anita
Center for Hematologic Malignancies, The Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Blood Marrow Transplant. 2016 Oct;22(10):1893-1899. doi: 10.1016/j.bbmt.2016.07.007. Epub 2016 Aug 2.
Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P < .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to HRM, higher stage, less than a CR pretransplant, lack of post-transplant therapy, and African American race were associated with worse OS. In conclusion, we show HRM patients achieve similar day 100 post-transplant responses compared with non-HRM patients, but these responses are not sustained. Post-transplant therapy appeared to improve the poor outcomes of HRM.
传统细胞遗传学和间期荧光原位杂交(FISH)可识别出预后较差的高危多发性骨髓瘤(HRM)人群。我们分析了在进行一线自体造血细胞移植(autoHCT)后,HRM人群与非HRM人群之间的这些差异。2008年至2012年期间,在国际血液和骨髓移植研究中心数据库中,共识别出715例经FISH和/或细胞遗传学数据确诊且接受一线autoHCT的多发性骨髓瘤患者。HRM被定义为存在17p缺失、t(4;14)、t(14;16)、亚二倍体(<45条染色体,不包括-Y)或1号染色体p臂和1q臂异常;其他所有患者为非HRM。在125例HRM患者(17.5%)中,与非HRM患者相比(56%对43%,P <.001),接受硼替佐米和免疫调节剂(IMiDs)诱导治疗的比例更高,移植前完全缓解(CR)率相似(14%对16%,P =.1)。移植后第100天,HRM患者至少达到非常好的部分缓解的比例为59%,非HRM患者为61%(P =.6)。更多HRM患者接受了硼替佐米和IMiDs的移植后治疗(26%对12%,P =.004)。HRM患者与非HRM患者移植后三年的无进展生存期(PFS)和总生存期(OS)率分别为37%对49%(P <.001)和72%对85%(P <.001)。三年时,接受和未接受移植后治疗的HRM患者的PFS分别为46%(95%置信区间[CI],33至59)和14%(95%CI,4至29),而在非HRM患者中,接受和未接受移植后治疗的PFS分别为55%(95%CI,49至62)和39%(95%CI,32至47);接受和未接受移植后治疗的HRM患者的OS率分别为81%(95%CI,70至90)和48%(95%CI,30至65),相比之下,非HRM患者接受和未接受移植后治疗的OS率分别为88%(95%CI,84至92)和79%(95%CI,73至85)。在接受移植后治疗的患者中,HRM和非HRM患者的OS无差异(P =.08)。除了HRM外,更高的分期、移植前未达到CR、未接受移植后治疗以及非裔美国人种族与更差的OS相关。总之,我们发现HRM患者与非HRM患者移植后第100天的反应相似,但这些反应无法持续。移植后治疗似乎改善了HRM患者的不良预后。