Martino E A, Palmieri S, Galli M, Derudas D, Mina R, Della Pepa R, Zambello R, Vigna E, Bruzzese A, Mangiacavalli S, Zamagni E, Califano C, Musso M, Conticello C, Cerchione C, Mele G, Di Renzo N, Offidani M, Tarantini G, Casaluci G M, Rago A, Ria R, Uccello G, Barilà G, Palumbo G, Pettine L, De Magistris C, Vincelli I D, Brunori M, Accardi F, Amico V, Amendola A, Fontana R, Bongarzoni V, Rossini B, Cotzia E, Gozzetti A, Rizzi R, Sgherza N, Curci P, Mancuso K, Reddiconto G, Maroccia A, Franceschini L, Bertuglia G, Nappi D, Barbieri E, Quaresima M, Petrucci M T, Di Raimondo F, Neri A, Tripepi G, Musto P, Morabito F, Gentile M
Department of Onco-hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Hematology Unit, Ospedale Cardarelli, Naples, Italy.
ESMO Open. 2025 Feb;10(2):104084. doi: 10.1016/j.esmoop.2024.104084. Epub 2025 Jan 7.
BACKGROUND: Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS). MATERIALS AND METHODS: This retrospective analysis included 247 Dara-R MM patients treated with EloPd. All patients were also refractory to lenalidomide, with 51.4% to a proteasome inhibitor, thus classified as triple-class refractory (TCR). Survival risk-scoring systems for PFS (progression-free risk score-PRS) and OS (survival risk score-SRS) were developed to stratify patients based on their risk profiles. RESULTS: The overall response rate was 52.6%, with a median PFS and OS of 6.6 and 17.0 months, respectively. The International Staging System (ISS) stages II and III, low hemoglobin (Hb) levels, the last therapy being daratumumab, and symptomatic relapse were identified as significant independent predictors of shorter PFS in multivariable analysis. In addition to advanced ISS stages, low Hb levels (<10.6 g/dl), symptomatic relapse, and refractory disease exhibited an independent negative impact on OS. Importantly, no significant differences in both PFS and OS were observed between TCR and non-TCR patients. Based on these multivariable analyses, we developed PRS and SRS according to the magnitude of the hazard ratio. In PRS, 10.1% were low-risk, 41.3% intermediate, 43.3% high, and 5.3% very high-risk. The 12-month PFS probabilities were 86.3% (low), 67.6% (intermediate), 52.9% (high), and 31.8% (very high). For SRS, 6.1% were low-risk, 47.8% intermediate, 19.4% high, and 26.7% very high. The 12-month OS probabilities were 90.9% (low), 75.7% (intermediate), 55.9% (high), and 32.6% (very high). CONCLUSIONS: This study supports EloPd as an effective treatment option in Dara-R MM patients, providing valuable disease control and acting as a potential bridge to newer therapies, such as CAR-T and bispecific antibodies.
背景：难治性达雷妥尤单抗多发性骨髓瘤（Dara-R MM）是一个重大的治疗挑战。本研究旨在评估埃罗妥珠单抗、泊马度胺和地塞米松（EloPd）在一大群真实世界的Dara-R MM患者中的疗效和生存结果，特别关注无进展生存期（PFS）和总生存期（OS）。 材料与方法：这项回顾性分析纳入了247例接受EloPd治疗的Dara-R MM患者。所有患者对来那度胺也耐药，51.4%对蛋白酶体抑制剂耐药，因此被归类为三重耐药（TCR）。开发了PFS（无进展风险评分-PRS）和OS（生存风险评分-SRS）的生存风险评分系统，以根据患者的风险特征对其进行分层。 结果：总缓解率为52.6%，中位PFS和OS分别为6.6个月和17.0个月。国际分期系统（ISS）II期和III期、低血红蛋白（Hb）水平、最后一次治疗为达雷妥尤单抗以及症状性复发在多变量分析中被确定为较短PFS的显著独立预测因素。除了晚期ISS分期外，低Hb水平（<10.6 g/dl）、症状性复发和难治性疾病对OS有独立的负面影响。重要的是，在TCR和非TCR患者之间，PFS和OS均未观察到显著差异。基于这些多变量分析，我们根据风险比的大小制定了PRS和SRS。在PRS中，10.1%为低风险，41.3%为中度风险，43.3%为高风险，5.3%为极高风险。12个月的PFS概率分别为86.3%（低风险）、67.6%（中度风险）、52.9%（高风险）和31.8%（极高风险）。对于SRS，6.1%为低风险，47.8%为中度风险，19.4%为高风险，26.7%为极高风险。12个月的OS概率分别为90.9%（低风险）、75.7%（中度风险）、55.9%（高风险）和32.6%（极高风险）。 结论：本研究支持EloPd作为Dara-R MM患者的一种有效治疗选择，可提供有价值的疾病控制，并作为通向诸如CAR-T和双特异性抗体等更新疗法的潜在桥梁。
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