Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
Department of Pathology, Puducherry, India.
Blood Cancer J. 2023 Mar 24;13(1):45. doi: 10.1038/s41408-023-00816-8.
Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is currently approved for relapsed-refractory multiple myeloma. This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of bortezomib, pomalidomide, and dexamethasone (VPd) induction for NDMM. We used Fleming's two-stage design for sample size calculation. We included transplant-eligible and ineligible patients aged 18-75 years in the study. The patients received four cycles of VPd induction followed by response assessment. Thirty-four patients were included in the study, of which 31 completed all four cycles of induction. The median age was 52 years (32-72). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had ISS-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Three patients had high-risk cytogenetic abnormalities. After four cycles of VPd induction, ten patients (32%) achieved stringent CR, nine had CR (29%), eight (26%) had VGPR, and 4 (13%) had PR. Fifteen (48%) had a complete metabolic response (CMR) on PET-CT. Two patients developed SAEs. Anemia was the most common hematological toxicity. Peripheral neuropathy and constipation were the most common non-hematological toxicities. Patients with ≥VGPR had significantly better 12-month PFS than those with PR. Patients with ≥VGPR and CMR on PET-CT had significantly better 12-month OS. Our study showed VPd induction is safe and efficacious in NDMM. Further Phase 3 studies are necessary to establish the superiority and survival benefits.
硼替佐米、来那度胺和地塞米松诱导化疗（VRd），随后进行自体干细胞移植（ASCT），是新诊断多发性骨髓瘤（NDMM）患者的标准治疗方法。泊马度胺目前被批准用于复发性/难治性多发性骨髓瘤。这项单臂、开放标签、2 期研究前瞻性评估了硼替佐米、泊马度胺和地塞米松（VPd）诱导治疗 NDMM 的疗效和安全性。我们使用弗莱明两阶段设计进行样本量计算。研究纳入了年龄在 18-75 岁的适合移植和不适合移植的患者。患者接受 4 个周期的 VPd 诱导治疗，然后进行疗效评估。研究共纳入 34 例患者，其中 31 例完成了所有 4 个周期的诱导治疗。中位年龄为 52 岁（32-72 岁）。30 例（91%）患者患有多发性骨髓瘤，3 例患者患有多发性浆细胞瘤，骨髓受累少于 10%。9 例（27%）患者为 ISS-I 期，9 例（27%）患者为 ISS-II 期，15 例（46%）患者为 ISS-III 期骨髓瘤。3 例患者存在高危细胞遗传学异常。VPd 诱导治疗 4 个周期后，10 例患者（32%）达到严格的完全缓解，9 例患者达到完全缓解，8 例患者（26%）达到非常好的部分缓解，4 例患者（13%）达到部分缓解。15 例患者（48%）在 PET-CT 上有完全代谢缓解。2 例患者发生严重不良事件。贫血是最常见的血液学毒性。周围神经病和便秘是最常见的非血液学毒性。达到≥非常好的部分缓解的患者 12 个月无进展生存率显著高于达到部分缓解的患者。在 PET-CT 上达到≥非常好的部分缓解和完全代谢缓解的患者 12 个月总生存率显著高于未达到该缓解标准的患者。本研究表明，VPd 诱导治疗在 NDMM 中安全有效。需要进一步的 3 期研究来确定其优越性和生存获益。
