Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN,Blood Cancer Journal

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Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2024-07-08 , DOI: 10.1038/s41408-024-01088-6
Ajai Chari ₁ , Jonathan L Kaufman ₂ , Jacob Laubach ₃ , Douglas W Sborov ₄ , Brandi Reeves ₅ , Cesar Rodriguez ₁ , Rebecca Silbermann ₆ , Luciano J Costa ₇ , Larry D Anderson ₈ , Nitya Nathwani ₉ , Nina Shah ₁₀ , Naresh Bumma ₁₁ , Sarah A Holstein ₁₂ , Caitlin Costello ₁₃ , Andrzej Jakubowiak ₁₄ , Tanya M Wildes ₁₂ , Robert Z Orlowski ₁₅ , Kenneth H Shain ₁₆ , Andrew J Cowan ₁₇ , Huiling Pei ₁₈ , Annelore Cortoos ₁₉ , Sharmila Patel ₁₉ , Thomas S Lin ₁₉ , Peter M Voorhees ₂₀ , Saad Z Usmani ₂₁ , Paul G Richardson ₃

Affiliation

Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
University of North Carolina-Department of Medicine-Chapel Hill, Chapel Hill, NC, USA.
Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
University of Alabama at Birmingham, Birmingham, AL, USA.
Myeloma, Waldenstrӧm's and Amyloidosis Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
University of California San Francisco, San Francisco, CA, USA.
Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
University of Chicago Medical Center, Chicago, IL, USA.
Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA, USA.
Janssen Research & Development, LLC, Titusville, NJ, USA.
Janssen Scientific Affairs, LLC, Horsham, PA, USA.
Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10⁻⁵) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06–1.48]), with HRCAs (0.38 [0.14–1.01]), and with gain/amp(1q21) (0.42 [0.14–1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35–1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM.

Video Abstract

中文翻译：

Daratumumab 在符合移植条件的新诊断多发性骨髓瘤患者中的作用：GRIFFIN 临床相关亚组的最终分析

随机 2 期 GRIFFIN 研究（NCT02874742）评估了 daratumumab 联合来那度胺/硼替佐米/地塞米松（D-RVd）在符合移植条件的新诊断多发性骨髓瘤（NDMM）中的疗效。我们提出了临床相关亚组的最终事后分析（中位随访，49.6 个月），包括根据修订后的定义（del[17p]、t[4;14]，t[14;16]，t[14;20] 和/或 gain/amp[1q21]）。患者接受 4 个诱导周期（D-RVd/RVd）、高剂量治疗/移植、2 个巩固周期（D-RVd/RVd）和来那度胺±达土尤单抗维持治疗（≤ 2 年）。在 65 ≥ 岁患者中，D-RVd 的微小残留病阴性（^10-5）率更高（67.9% 对 17.9%），HRCA （54.8% 对 32.4%）和增益/安培（1q21）（61.8% 对 28.6%）。D-RVd 显示，在 65 岁（0.29 [0.06-1.48]）、HRCA （0.38 [0.14-1.01]）和增益/安培（1q21）（0.42 [0.14-1.27]）患者中，无进展生存期≥ RVd 有改善的趋势。在功能性高危亚组（巩固结束时非 MRD 阴性）中，风险比为 0.82 （0.35-1.89）。在 65 ≥患者中，D-RVd 的 3/4 级治疗中出现的不良事件（TEAE）发生率高于 RVd （88.9% 对 77.8%），导致停止 ≥ 1 治疗成分的 TEAE 也是如此（37.0% 对 25.9%）。1 例 D-RVd 患者死于无关的 TEAE。这些结果支持在符合移植条件的高危 NDMM 患者中将 daratumumab 添加到 RVd 中。

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更新日期：2024-07-08

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