Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR <30 mL/min/1.73 m2or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55–89) years, with a median GFR of 20.1 mL/min/1.73 m2(interquartile range, 9.4–27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1–10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n= 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI.
肾功能损害是多发性骨髓瘤的常见并发症。然而，关于抗骨髓瘤治疗方案在严重肾功能损害患者中的安全性和有效性数据有限，因为这类患者常被排除在临床试验之外。这项研究者发起的多中心II期GMMG-DANTE试验评估了达雷妥尤单抗、硼替佐米和地塞米松联合方案在伴有严重肾功能损害的复发或难治性多发性骨髓瘤患者中的疗效。研究纳入既往接受过至少一线治疗、肾小球滤过率＜30 mL/min/1.73 m²或正在接受血液透析的复发难治性多发性骨髓瘤患者，给予8个周期DVd方案治疗后进行达雷妥尤单抗维持治疗。该试验在计划入组36例患者中完成22例后提前终止。主要终点为总缓解率。患者中位年龄70岁（范围55-89岁），中位肾小球滤过率为20.1 mL/min/1.73 m²（四分位距9.4-27.3 mL/min/1.73 m²），其中8例患者接受血液透析。既往治疗线数中位值为2线（范围1-10）。尽管试验提前终止，但仍达到主要终点，总缓解率为67%（14/21），其中部分缓解、非常好的部分缓解和完全缓解率分别为29%、29%和10%（例数分别为6、6、2）。14例患者（67%）获得肾脏缓解。中位随访28个月后，中位无进展生存期为10.4个月，中位总生存期尚未达到。高级别毒性主要为血液学毒性，≥3级的非血液学毒性以感染为主（24%）。这项专门针对严重肾功能损害复发难治性多发性骨髓瘤患者的前瞻性GMMG-DANTE试验表明，DVd方案的疗效和安全性数据与无肾功能损害患者的数据具有可比性。
肿瘤(癌症)患者之家