A Phase II Clinical Study for Evaluating the Efficacy and Safety of Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone in Transplantation-Eligible Elderly Patients with Newly Diagnosed Multiple Myeloma (KMM2101)
Authors: Yoon Sang Eun , Jung Sung-Hoon , Lee Gyeong Won , Min Chang-Ki , Byun Ja Min , Kwak Jae-Yong , Lee Myung-Won , Lee Ho Sup , Kim Seok Jin , Kim Kihyun 
Published: December 2024

Background: Patients aged 65-69 years old with newly diagnosed multiple myeloma (NDMM) are enrolled in both transplant-eligible and transplant-ineligible trials. The use of autologous hematopoietic stem cell transplantation (Auto-HCT) for NDMM patients in this age group is still controversial, especially in the era of four-drug induction treatment. Thus, we investigated the role of induction therapy with four-drug regimens, consisting of daratumumab, bortezomib, lenalidomide, and dexamethasone(D-VRd), Auto-HCT followed by maintenance therapy in 65-69-year-old NDMM patients.
Methods: This study targets NDMM patients aged 65-69 years suitable for Auto-HCT. The treatment consists of six cycles of induction of D-VRd followed by Auto-HCT, maintenance composed of 1 year of lenalidomide and two years of daratumumab. The primary outcome is the proportion of patients who achieved very good partial response (VGPR) or higher outcomes after six cycles of induction therapy. The secondary outcome was minimal residual disease (MRD), conducted three times for the patients who achieved VGPR or higher response rate after Auto-HCT using next-generation flow (NGF)-based MRD technology with a sensitivity of 10−5. Additional secondary outcomes were overall response rate (ORR), complete remission (CR), progression-free survival (PFS), and overall survival (OS). We also analyzed the safety of patients using this protocol.
Results: A total of 26 patients enrolled in this study. The median age was 66 (65-69), and the number of female patients was 14 (53.8%). Twenty-five patients (96.2%) were constituted ECOG-PS 0-1. Fourteen patients (56.8%) had ISS stage II, and five (19.2%) had ISS stage III. Seventeen patients (65.4%) were R-ISS stage II, and four (15.4%) were R-ISS stage III. At diagnosis, 19 (73.1%) patients had bony lytic lesions and 4(15.4%) patients had extramedullary disease (EMD). After six cycles of induction therapy, twenty-four patients (92.3%) achieved VGPR. We collected hematopoietic stem/progenitor cells (HSPCs) after four induction cycles, and the median of CD34 cells was 2.936 ⅹ106/kg (range 0.7-6.8). The median neutrophil engraftment date was 12 days (range 10-16). A patient did not receive auto-SCT after six induction cycles and withdrew from the study due to poor performance. Twenty-five patients were eligible for the response after transplantation. The responses after transplantation are VGPR (21, 80.8%) and CR (3, 11.5%). After auto-HCT twenty-one (84.0%) achieved MRD-negative. During 15.8 months of median follow-up duration, a patient experienced disease progression and another patient who achieved CR after auto-HCT died suddenly for an unknown reason. The PFS did not reach the median value. Regarding safety issues, the percentage of all grade and grade 3/4 thrombocytopenia was 34.6% (n=9) and 23.1% (n=6). Any grade of peripheral sensory neuropathy was observed in 5 cases (19.2%).
Discussion: This phase II KMM2101 study, which consisted of D-VRD induction followed by ASCT and maintenance, demonstrated a considerable response of VGPR or higher and 84% of MRD-negative and manageable toxicities for auto-HCT-eligible NDMM patients with age 65-69.