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3388 Daratumumab, Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) Alone in Transplant-Ineligible Asian Patients with Newly Diagnosed Multiple Myeloma: Final Analysis of the Phase 3 Octans StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Combination therapy, Diseases, Therapies, Adverse Events, Myeloid Malignancies, Study Population, Human, Minimal Residual Disease
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Weijun Fu1*, Soo-Mee Bang, MD, PhD2, Honghui Huang, PhD, MD3*, Kihyun Kim4*, Wei Li5*, Gang An6*, Je-Jung Lee7*, Zhen Cai8*, Jie Jin9, Yafei Wang10*, Chor Sang Chim, MD, PhD, BMBS11*, Robin Carson, MD, BA12, Rui Liu13*, Lingling Wang14*, Man Zhao15*, XI Chen, PhD16*, Canchan Cui17*, Jian Hou3* and Jianxiang Wang, MD6

1Shanghai Changzheng Hospital, Shanghai, China
2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, KOR
3Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
4Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)
5The First Hospital of Jilin University, Changchun, China
6Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
7Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun, Korea, Republic of (South)
8Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
9The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
10Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
11Hong Kong Sanatorium & Hospital, Hong Kong, China
12Janssen Research & Development, LLC, Spring House, PA
13Johnson & Johnson China Ltd, Beijing, China
14Janssen China Research and Development, Beijing, China
15IQVIA, Shanghai, China
16Xian Janssen Pharmaceutical Ltd.; Xian Janssen Pharmaceutical Ltd., Beijing; Shanghai, China
17Xian Janssen Pharmaceutical Ltd., Beijing, China

Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action and has shown clinical efficacy for the treatment of multiple myeloma (MM). In an updated analysis of the global phase 3 ALCYONE study, D-VMP demonstrated a significant progression-free survival (PFS) benefit compared to VMP in transplant-ineligible patients with newly diagnosed MM (NDMM). A prior analysis of the phase 3 OCTANS study (median follow-up, 12.3 months) also showed a favorable clinical benefit/risk profile for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM. Here, we report results from the final analysis of OCTANS, with a median follow-up of >3 years.

Methods: The randomized, phase 3 OCTANS study (NCT03217812) enrolled Asian patients with NDMM who were ineligible for autologous stem-cell transplant due to age or presence of comorbidities. Patients were randomized 1:2 (VMP:D-VMP) to receive up to nine 42-day cycles of VMP (bortezomib 1.3 mg/m2 SC twice weekly in Cycle 1 and weekly in Cycles 2-9, and melphalan 9 mg/m2 and prednisone 60 mg/m2 orally on Days 1-4 of each cycle) or D-VMP (VMP + daratumumab 16 mg/kg IV weekly in Cycle 1, every 3 weeks in Cycles 2-9, and every 4 weeks thereafter until disease progression). Per a protocol amendment, patients receiving daratumumab IV were permitted to switch to daratumumab SC 1,800 mg (same schedule as IV) on Day 1 of any cycle. The primary endpoint was achievement of a very good partial response (VGPR) or better.

Results: A total of 220 patients were randomized to D-VMP (n = 146) or VMP (n = 74). At the time of the final analysis, with a median follow-up of 41.2 months, the rate of VGPR or better was significantly higher with D-VMP versus VMP (80.1% vs 47.3%; P <0.0001; Table). The rate of measurable residual disease negativity (10–5) was also higher with D-VMP versus VMP (40.4% vs 10.8%; P <0.0001). D-VMP continued to show a significant improvement in PFS versus VMP (median, 38.7 vs 19.2 months; HR, 0.35; 95% CI, 0.23-0.52; P <0.0001; Table, Figure), as well as a longer time to subsequent antimyeloma therapy (median, 46.8 vs 20.6 months; HR, 0.31; 95% CI, 0.20-0.47; P <0.0001). However, median overall survival was not yet reached for either group. The overall safety profile of D-VMP was consistent with that observed for the primary analysis. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported for 133 (92.4%) patients who received D-VMP and 60 (84.5%) patients who received VMP and were primarily hematologic events; nonhematologic grade 3/4 TEAEs in ≥10% of patients included pneumonia (D-VMP, 31.3% vs VMP, 18.3%), hypokalemia (15.3% vs 4.2%), and hypertension (13.2% vs 8.5%). Grade 3/4 infection TEAEs were reported for 67 (46.5%) and 22 (31.0%) patients who received D-VMP or VMP, respectively. Serious TEAEs were reported for 75 (52.1%) and 28 (39.4%) patients in the D-VMP and VMP groups, respectively, and TEAEs led to treatment discontinuation in 6 (4.2%) and 4 (5.6%) patients, respectively. The incidence of infusion-related reaction TEAEs in the D-VMP group was 33.3%, which is consistent with that previously reported for daratumumab; most events were of grade 1 or 2 severity. The risk of immunogenicity to daratumumab was low, with 1 of 130 evaluable patients testing positive for daratumumab antibodies. Within the D-VMP group, 76 patients switched from daratumumab IV to SC administration. Among these patients, 64 (84.2%) patients preferred SC administration, 7 (9.2%) preferred IV administration, and 15 (19.7%) had no preference on ≥1 of 2 surveys. Of the 64 patients who preferred SC administration, primary reasons included treatment administration time (84.4%), more comfortable administration process (57.8%), less caregiver burden (31.2%), and fewer administration-related reactions (26.6%).

Conclusions: With a median follow-up of >3 years, this final analysis of OCTANS demonstrated a continued clinical benefit with D-VMP versus VMP in Asian patients, with PFS improvement comparable to that observed in the global ALCYONE study (HR, 0.35 vs 0.42, respectively). No new safety concerns were identified for D-VMP with extended follow-up. In addition, daratumumab SC administration was preferred by the majority of patients who switched from daratumumab IV. These results further support the use of daratumumab IV or SC in combination with VMP in transplant-ineligible Asian patients with NDMM.

Disclosures: Huang: Janssen Pharmaceutical Ltd: Speakers Bureau. Carson: Janssen Research & Development, LLC: Current Employment. Liu: Johnson & Johnson China Ltd: Current Employment, Current holder of stock options in a privately-held company. Wang: Janssen China Research and Development: Current Employment, Current holder of stock options in a privately-held company. Chen: Xian Janssen Pharmaceutical Ltd.: Current Employment, Current holder of stock options in a privately-held company. Cui: Xian Janssen Pharmaceutical Ltd.: Current Employment, Current holder of stock options in a privately-held company.

*signifies non-member of ASH