Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Transplant Cell Ther. 2022 Nov;28(11):752.e1-752.e6. doi: 10.1016/j.jtct.2022.07.028. Epub 2022 Aug 5.
Maintenance therapy with single-agent lenalidomide (Len) after autologous hematopoietic stem cell transplantation (autoHCT) for multiple myeloma (MM) is associated with improved progression-free survival (PFS). However, MM patients with high-risk chromosomal abnormalities (HRMMs) may need a more intense regimen. We hypothesized that adding another antimyeloma drug to Len maintenance would lead to improved outcomes. We conducted this retrospective single-center chart review analysis of adult HRMM patients who underwent autoHCT between 2008 and 2018, followed by Len-based maintenance therapy. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. We divided patients into those who received either single-agent Len maintenance (Len-only) or Len-based combinations (Len-combo). We compared nonrelapse mortality, day 100 and best post-transplantation responses, minimal residual disease status, PFS, and overall survival (OS) between the 2 groups. We also performed sensitivity analyses using inverse probability weights to correct for potential bias owing to nonrandomization of the 2 groups. A total of 231 patients with HRMM were included in our analysis, with a median age of 62.4 years (range, 33.5 to 79.9 years), and 55% were male. There were 153 patients in the Len-only group and 78 in the Len-combo group. Len-combo regimens were either doublets (Len with dexamethasone [dex] [n = 10], elotuzumab [n = 28], or ixazomib [n = 14]) or triplets (Len with bortezomib/dex [n = 10], ixazomib/dex [n = 10], or carfilzomib/dex [n = 6]). More patients in the Len-combo group had ≥2 high-risk cytogenetic abnormalities compared with the Len-only group (32% versus 12%: P < .001). The median duration of follow-up was 40.7 months in the Len-only group and 37.0 months in the Len-combo group. For all patients, the median PFS was 25.5 months, and the median OS was 82.6 months. There was no significant between-group difference in PFS (hazard ratio [HR] 1.01; 95% confidence interval [CI], .71-1.44; P = .94) or OS (HR, .84; 95% CI, .49 to 1.43; P = .52). However, for patients with high-risk cytogenetic abnormalities other than 1q+, there was a trend toward better PFS in the Len-combo group (HR, .59; 95% CI, .32 to 1.09; P = .09), but no difference in OS (HR, .79; 95% CI, .37 to 1.65; P = .53). In this single-center retrospective analysis, the use of Len-based combinations for post-transplantation maintenance was not associated with improved outcomes in HRMM patients; however, there was a trend toward improved PFS in patients with high-risk abnormalities other than 1q+.
自体造血干细胞移植（autoHCT）后，采用来那度胺（Len）单药维持治疗多发性骨髓瘤（MM）可改善无进展生存期（PFS）。然而，具有高危细胞遗传学异常（HRMMs）的 MM 患者可能需要更强烈的治疗方案。我们假设在 Len 维持治疗中添加另一种抗骨髓瘤药物将改善治疗结果。我们进行了这项回顾性单中心图表审查分析，纳入了 2008 年至 2018 年间接受 autoHCT 且随后接受基于 Len 的维持治疗的 HRMM 成年患者。高危细胞遗传学定义为 del(17p)、t(4;14)、t(14;16)、1q21 获得或荧光原位杂交（FISH）扩增。我们将患者分为接受单药 Len 维持治疗（Len-only）或基于 Len 的联合治疗（Len-combo）的两组。我们比较了两组患者的非复发死亡率、第 100 天和最佳移植后反应、微小残留疾病状态、PFS 和总生存期（OS）。我们还使用逆概率权重进行敏感性分析，以纠正由于两组非随机化而导致的潜在偏差。共有 231 例 HRMM 患者纳入我们的分析，中位年龄为 62.4 岁（范围为 33.5 至 79.9 岁），55%为男性。Len-only 组有 153 例患者，Len-combo 组有 78 例患者。Len-combo 方案为双联方案（Len 联合地塞米松[dex] [n=10]、依鲁替尼[n=28]或伊沙佐米[n=14]）或三联方案（Len 联合硼替佐米/dex [n=10]、伊沙佐米/dex [n=10]或卡非佐米/dex [n=6]）。与 Len-only 组相比，Len-combo 组有更多患者具有≥2 种高危细胞遗传学异常（32%比 12%：P<0.001）。Len-only 组的中位随访时间为 40.7 个月，Len-combo 组为 37.0 个月。对于所有患者，中位 PFS 为 25.5 个月，中位 OS 为 82.6 个月。两组患者在 PFS（风险比[HR]1.01；95%置信区间[CI]，0.71-1.44；P=0.94）或 OS（HR，0.84；95%CI，0.49 至 1.43；P=0.52）方面无显著差异。然而，对于除 1q+以外的具有高危细胞遗传学异常的患者，Len-combo 组的 PFS 有改善趋势（HR，0.59；95%CI，0.32 至 1.09；P=0.09），但 OS 无差异（HR，0.79；95%CI，0.37 至 1.65；P=0.53）。在这项单中心回顾性分析中，在 HRMM 患者中，采用基于 Len 的联合方案进行移植后维持治疗并未改善治疗结果；然而，在具有除 1q+以外的高危异常的患者中，PFS 有改善趋势。
