Banerjee Rahul, Sexton Rachael, Cowan Andrew J, Rosenberg Aaron S, Ailawadhi Sikander, Rajkumar S Vincent, Kumar Shaji, Dispenzieri Angela, Lonial Sagar, Durie Brian G M, Richardson Paul G, Usmani Saad Z, Hoering Antje, Orlowski Robert Z
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Division of Hematology/Oncology, University of Washington, Seattle, WA.
Blood. 2025 Jan 2;145(1):75-84. doi: 10.1182/blood.2024025939.
Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned dexamethasone intensity was 40 to 60 mg weekly in all arms. Patients were categorized into FD-DEX (full-dose dexamethasone maintained throughout induction) or LD-DEX (lowered-dose dexamethasone or discontinuation; only permitted for grade 3+ toxicities per both study protocols). Of the 541 evaluated patients, the LD-DEX group comprised 373 patients (69%). There were no differences in PFS or OS between the FD-DEX and LD-DEX groups, which were balanced in terms of age, stage, and performance status. Predictors of PFS and OS in the multivariate models were treatment arm, age ≥70 years, and thrombocytopenia. FD-DEX did not significantly improve either outcome. Our study suggests that dexamethasone dose reductions are common in multiple myeloma, even within clinical trials. Given the many toxicities and unclear benefits of dexamethasone in the era of modern treatment regimens, dexamethasone dose reduction during NDMM induction warrants further prospective studies. These trials were registered at www.clinicaltrials.gov as #NCT00644228 and NCT01668719.
地塞米松是新诊断多发性骨髓瘤（NDMM）诱导治疗的关键组成部分，尽管存在常见毒性，包括高血糖和失眠。在随机的ECOG E4A03试验中，每周一次40毫克地塞米松与较低剂量相比死亡率更低。然而，在NDMM中，低于该阈值的地塞米松剂量减少对无进展生存期（PFS）和总生存期（OS）的影响尚未完全明确。我们对SWOG 0777和SWOG 1211两项NDMM研究进行了二次汇总分析，这两项研究单独使用来那度胺和地塞米松（Rd），联合或不联合硼替佐米，联合或不联合埃罗妥珠单抗。所有治疗组计划的地塞米松强度为每周40至60毫克。患者被分为FD-DEX组（诱导期全程维持全剂量地塞米松）或LD-DEX组（降低剂量地塞米松或停药；仅在两项研究方案规定的3级及以上毒性时允许）。在541例评估患者中，LD-DEX组包括373例患者（占69%）。FD-DEX组和LD-DEX组在PFS或OS方面没有差异，两组在年龄、分期和体能状态方面均衡。多变量模型中PFS和OS的预测因素是治疗组、年龄≥70岁和血小板减少症。FD-DEX组并未显著改善任何一项结果。我们的研究表明，地塞米松剂量减少在多发性骨髓瘤中很常见，即使在临床试验中也是如此。鉴于在现代治疗方案时代地塞米松存在诸多毒性且益处不明确，NDMM诱导期地塞米松剂量减少值得进一步进行前瞻性研究。这些试验已在www.clinicaltrials.gov注册，注册号为#NCT00644228和NCT01668719。
