Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk,Blood Cancer Journal

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Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2024-04-22 , DOI: 10.1038/s41408-024-01030-w
Natalie S Callander ₁ , Rebecca Silbermann ₂ , Jonathan L Kaufman ₃ , Kelly N Godby ₄ , Jacob Laubach ₅ , Timothy M Schmidt ₁ , Douglas W Sborov ₆ , Eva Medvedova ₂ , Brandi Reeves ₇ , Binod Dhakal ₈ , Cesar Rodriguez ₉ , Saurabh Chhabra ₈ , Ajai Chari ₉ , Susan Bal ₄ , Larry D Anderson ₁₀ , Bhagirathbhai R Dholaria ₁₁ , Nitya Nathwani ₁₂ , Parameswaran Hari ₈ , Nina Shah ₁₃ , Naresh Bumma ₁₄ , Sarah A Holstein ₁₅ , Caitlin Costello ₁₆ , Andrzej Jakubowiak ₁₇ , Tanya M Wildes ₁₅ , Robert Z Orlowski ₁₈ , Kenneth H Shain ₁₉ , Andrew J Cowan ₂₀ , Huiling Pei ₂₁ , Annelore Cortoos ₂₂ , Sharmila Patel ₂₂ , Thomas S Lin ₂₂ , Smith Giri ₂₃ , Luciano J Costa ₄ , Saad Z Usmani ₂₄ , Paul G Richardson ₅ , Peter M Voorhees ₂₅

Affiliation

University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Winship Cancer Institute, Emory University, Atlanta, GA, USA.
University of Alabama at Birmingham Hospital, Birmingham, AL, USA.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA.
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Myeloma, Waldenstrӧm's and Amyloidosis Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
Vanderbilt University Medical Center, Nashville, TN, USA.
Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Department of Medicine, 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 & 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.
Division of Medical Oncology, University of Washington, Seattle, WA, USA.
Janssen Research & Development, LLC, Titusville, NJ, USA.
Janssen Scientific Affairs, LLC, Horsham, PA, USA.
Division of Hematology & Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Levine Cancer Institute, Atrium Health Wake Forest Baptist, Charlotte, NC, USA.

In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10^–5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs).

Video Abstract

中文翻译：

基于 Daratumumab 的四联疗法治疗符合移植条件且细胞遗传学风险高的新诊断多发性骨髓瘤

在 MASTER 研究（NCT03224507）中，daratumumab + 卡非佐米/来那度胺/地塞米松（D-KRd）在符合移植条件的新诊断多发性骨髓瘤（NDMM）中显示出良好的疗效。在 GRIFFIN （NCT02874742）中，daratumumab + 来那度胺/硼替佐米/地塞米松（D-RVd）改善了符合移植条件的 NDMM 的结局。在这里，我们介绍了高危细胞遗传学异常（HRCAs;del[17p]、t[4;14]，t[14;16]，t[14;20] 或 gain/amp[1q21]）。在 123 例 D-KRd 患者中，43.1% 、 37.4% 和 19.5% 的患者有 0 、 1 或 ≥2 个 HRCA。在 120 例 D-RVd 患者中，55.8% 、 28.3% 和 10.8% 的患者有 0 、 1 或 ≥ 2 个 HRCA。D-KRd 的 0、1 或 ≥2 HRCA 的完全缓解率或更好（研究最佳）率为 90.6%、89.1% 和 70.8%，D-RVd 为 90.9%、78.8% 和 61.5%。在中位随访时（MASTER，31.1 个月;GRIFFIN，随机患者为 49.6 个月/安全磨合患者为 59.5 个月），通过下一代测序（^10-5）评估的 MRD 阴性率为 80.0%、86.4% 和 83.3%，D-KRd 为 0、1 或 ≥2 HRCA，D-RVd 为 76.1%、55.9% 和 61.5%。PFS 在研究之间相似，0 或 1 优于 ≥2 HRCA：D-KRd 的 36 个月 PFS 率为 89.9%， D-RVd 为 86.2%、52.4% 和 96.7%、90.5% 和 53.5%。这些数据支持对符合移植条件的 HCRA NDMM 使用含 daratumumab 的方案;然而，对于超高危疾病（≥2 HRCA），需要额外的策略。

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更新日期：2024-04-22

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