卡非佐米治疗多发性骨髓瘤的疗效和毒性:单一机构经验

R. Thakur, N. Kohn, Brown Mh
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引用次数: 0

摘要

Carfilzomib是一种不可逆蛋白酶体抑制剂(PI),于2012年首次被批准用于治疗复发性难治性多发性骨髓瘤(RRMM)。评估卡非佐米在治疗RRMM中的实际应用是很重要的。本研究的目的是评估carfilzomib治疗的RRMM患者的总缓解率(ORR)、无进展生存期(PFS)和药物不良事件(ADEs)的实际结果,包括心脏毒性和肾毒性。我们回顾性分析了2013年1月至2018年12月期间卡非佐米治疗的MM诊断患者的图表。收集了人口统计学、细胞遗传学、荧光原位杂交(FISH)和治疗史。66例患者符合研究标准,中位年龄65岁(范围48 - 84岁)。使用修订的国际分期系统(R-ISS), 7例(10.6%)患者为I期,28例(42.4%)为II期,31例(47.0%)为III期。细胞遗传学显示33例(48.5%)为高危。8例(12.12%)患者接受了4种以上的治疗,27例(40.95)患者在卡非佐米之前接受了自体干细胞移植(ASCT)。先前的治疗包括来那度胺、硼替佐米和环磷酰胺为主的方案。ORR为77.2%,完全缓解(CR) 4例(6.2%)。10例患者(15%)在卡非佐米治疗疾病进展(POD)后接受ASCT。大多数POD患者接受达拉单抗(40%)或泊马度胺(46%)治疗。2级高血压9例(13.6%),急性肾衰竭(ARF) 11例(16.7%),心力衰竭(HF) 12例(18.2%)。卡非佐米的中位PFS为6.96个月。该研究显示卡非佐米改善了RRMM患者的PFS;然而,心脏和肾脏毒性的风险增加,比以前文献报道的要大。这项研究强调了肿瘤学家意识到这些毒性的重要性。敏锐的意识、早期监测和预防可能会对卡非佐米的使用结果产生有利影响。
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Treatment Outcomes and Toxicity Profile of Carfilzomib in Multiple Myeloma: A Single Institution Experience
Carfilzomib is an irreversible proteasome inhibitor (PI), first approved in 2012 for treatment of relapsed refractory multiple myeloma (RRMM). The real-world use of carfilzomib in treatment of RRMM is important to assess. The objectives of this study are to evaluate the real-world outcome in overall response rates (ORR), progression-free survival (PFS), and adverse drug events (ADEs), including cardiotoxicity and nephrotoxicity for RRMM patients treated with carfilzomib. We retrospectively analyzed the charts of patients with a diagnosis of MM treated with carfilzomib between January 2013 and December 2018. Demographics, cytogenetics, fluorescence in situ hybridization (FISH), and treatment history were collected. Sixty-six patients fit the study criteria, with median age of 65 years (range 48 - 84). Using the Revised International Staging System (R-ISS), 7 (10.6%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) stage III. Cytogenetics showed 33 (48.5%) were high risk. Eight (12.12%) patients were pretreated with more than 4 treatment lines and 27 (40.95) had an autologous stem cell transplant (ASCT) prior to carfilzomib. Prior treatments included lenalidomide, bortezomib, and cyclophosphamide-based regimens. The ORR was 77.2%, with 4 (6.2%) complete responses (CR). Ten patients (15%) received ASCT after carfilzomib for progression of disease (POD). The majority with POD received daratumumab (40%) or pomalidomide (46%). Grade 2 hypertension was noted in 9 (13.6%) patients, acute renal failure (ARF) in 11 (16.7%) and heart failure (HF) in 12 (18.2%). The median PFS on Carfilzomib was 6.96 months. This study showed carfilzomib improved PFS in patients with RRMM; however, there is increased risk for cardiac and renal toxicity, greater than previously reported in the literature. This study reinforces the importance for oncologists to be aware of these toxicities. Astute awareness, early monitoring, and prevention may favorably impact outcomes with use of carfilzomib.
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