Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma.
Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma.
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DOI：
10.1093/oncolo/oyad053
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发表时间：
2023-05-08
期刊：
影响因子：
5.8
通讯作者：
Kumar, Shaji
中科院分区：
文献类型：
--
作者：
Fonseca, Rafael;Facon, Thierry;Hashim, Mahmoud;Nair, Sandhya;He, Jianming;Ammann, Eric;Lam, Annette;Wildgust, Mark;Kumar, Shaji
关键词：
由于新诊断的多发性骨髓瘤 (NDMM) 患者并不总是接受一线 (1L) 治疗以外的任何治疗，因此患者必须在 1L 环境中接受最佳治疗。然而，最佳的初始治疗仍有待确定。我们进行了临床模拟来评估不同治疗顺序的潜在结果。我们使用分区生存模型来比较总生存期 (OS)：1L 中使用 (1) 达雷木单抗、来那度胺和地塞米松 (D-Rd)，随后在二线中使用基于泊马度胺或卡非佐米的方案 (2L) 与 (2) 1L 中使用硼替佐米、来那度胺和地塞米松 (VRd)，然后在二线中使用基于达雷木单抗的方案的总生存期 (OS) 2L 对比 (3) 1L 中来那度胺和地塞米松 (Rd)，随后 2L 中基于达雷妥尤单抗的治疗方案。健康状态（1L、2L+ 和死亡）之间转变的概率基于已发布的临床数据和来自 Flatiron Health 数据库的真实数据。基本案例中 1L 后停止治疗的患者比例（自然流失率）是使用 MAIA 试验的数据通过二项式逻辑模型进行估计的。与将基于达雷妥尤单抗的治疗方案延迟至 VRd 或 Rd 后 2L 相比，在 1L 中使用 D-Rd 可获得更长的中位 OS（8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] 或 5.75 [4.50-7.25] 年）。情景分析的结果与基本案例一致。我们的模拟结合了临床代表性治疗和损耗率，支持在不适合移植的 NDMM 患者中使用 D-Rd 作为初始治疗，而不是推迟使用达雷妥尤单抗直至后续治疗。 对于不适合自体干细胞移植的新诊断多发性骨髓瘤患者，最佳初始治疗仍有待确定。本文评估了不同治疗顺序的潜在结果。
Because patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences. We used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in second line (2L) versus (2) bortezomib, lenalidomide, and dexamethasone (VRd) in 1L followed by a daratumumab-based regimen in 2L versus (3) lenalidomide and dexamethasone (Rd) in 1L followed by a daratumumab-based regimen in 2L. Probabilities of transition between health states (1L, 2L+, and death) were based on published clinical data and real-world data from the Flatiron Health database. The proportion of patients discontinuing treatment after 1L (attrition rates) in the base case was estimated with a binomial logistic model using data from the MAIA trial. Using D-Rd in 1L conferred a longer median OS compared with delaying daratumumab-based regimens until 2L after VRd or Rd, respectively (8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] or 5.75 [4.50-7.25] years). Results of scenario analyses were consistent with the base case. Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of D-Rd as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible NDMM. Optimal initial treatment for newly diagnosed multiple myeloma in patients ineligible for autologous stem cell transplant remains to be identified. This article assesses potential outcomes with different treatment sequences.
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影响因子：
12.8
作者：
Durie BGM;Kumar SK;Usmani SZ;Nonyane BAS;Ammann EM;Lam A;Kobos R;Maiese EM;Facon T
通讯作者：
Facon T
影响因子：
3.7
作者：
Szabo AG;Klausen TW;Levring MB;Preiss B;Helleberg C;Breinholt MF;Hermansen E;Gjerdrum LMR;Bønløkke ST;Nielsen K;Kjeldsen E;Iversen KF;Teodorescu EM;Dokhi M;Kurt E;Strandholdt C;Andersen MK;Vangsted AJ
通讯作者：
Vangsted AJ
影响因子：
12.8
作者：
Ravi P;Kumar SK;Cerhan JR;Maurer MJ;Dingli D;Ansell SM;Rajkumar SV
通讯作者：
Rajkumar SV
影响因子：
6.5
作者：
Yong K;Delforge M;Driessen C;Fink L;Flinois A;Gonzalez-McQuire S;Safaei R;Karlin L;Mateos MV;Raab MS;Schoen P;Cavo M
通讯作者：
Cavo M
影响因子：
45.3
作者：
Patel, Kishan K.;Giri, Smith;Huntington, Scott F.
通讯作者：
Huntington, Scott F.