Division of Hematology,University of Torino, AOU Città della Salute e della Scienza di Torino.
Hematology, Dept. of Cellular Biotechnologies and Hematology, Sapienza University of Rome, IT.
Haematologica. 2021 Apr 1;106(4):1079-1085. doi: 10.3324/haematol.2019.243428.
Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).
尽管在过去几十年中多发性骨髓瘤的治疗取得了显著进展，但与标准风险患者相比，携带高危细胞遗传学异常的患者的预后仍然不佳。蛋白酶体抑制剂已被证明可部分改善高危患者的预后。我们汇总了两项关于不适合接受移植的多发性骨髓瘤患者的 I/II 期试验的数据，这些患者在接受卡非佐米联合环磷酰胺和地塞米松的初始治疗后，再接受卡非佐米维持治疗。本分析的目的是比较通过荧光原位杂交（FISH）分析检测到的标准风险与高危细胞遗传学异常患者的治疗结果。高危定义为存在至少一种染色体异常，包括 t(4;14)、del17p 和 t(14;16)。总体而言，94 名患者纳入了分析：标准风险组 57 名（61%），高危组 37 名（39%）。中位随访时间为 38 个月。在标准风险与高危患者中，我们观察到相似的无进展生存期（3 年 PFS：分别为 52%和 43%；p=0.50）、总生存期（3 年 OS：分别为 78%和 73%；p=0.38）和总缓解率（88%和 95%；p=0.47），两组之间无统计学差异。del17p 缺失患者与无缺失患者的无进展生存期无差异。卡非佐米，无论是作为诱导剂还是维持剂，用于不适合移植的新诊断多发性骨髓瘤患者，减轻了高危细胞遗传学带来的不良预后，并产生了与标准风险患者相似的无进展生存期和总生存期。临床试验注册号：NCT01857115（IST-CAR-561）和 NCT01346787（IST-CAR-506）。
