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4754 Renal Response of Selinexor, Pomalidomide, Bortezomib and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients with Renal Impairment: A Prospective, Open-Label, Multicenter, Phase 2 Study

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, registries
Monday, December 11, 2023, 6:00 PM-8:00 PM

Huixing Zhou1*, Long Chang2*, Jing Jia3*, Jie Ma4*, Hua Xue5*, Hao Li6*, Wenrong Huang7, Hebing Zhou8*, Jingnan Sun9*, Liping Su10*, Yanping Ma, PhD11*, Huang Hongming12*, Hongmei Jing13*, Zhenling Li14*, Guangyu Ma15*, Guohong Su16*, Jihao Zhou, MD17*, Biyun Chen18*, LI Bao19*, Zhihua Zhang, MD20*, Lin Yang21*, Haiping Yang22*, Yanhong Zhao23*, Chunyan Sun24*, Qingming Wang25*, Qimuge Saiyin26*, Da Gao, MD27*, Xiaoxia Chu, MD28*, Zhenfang Xi29*, Weiwei Tian, MD, PhD30*, Xuliang Shen, MD31*, Shi Minxia, MD, PhD32*, Jin Zhang33*, Yi Chen34*, Jingbo Xu35*, Yao Liu, PhD, MD36, Hongling Peng37*, Weijun Fu38*, Jun Luo, DO39*, Zhenyu Li40*, Hui-Han Wang41*, Xiaobo Wang42*, Xiuli Sun43*, Jinqiao Zhang44*, Wei WANG, MD, PhD45*, Yan Yan46*, Yafei Wang47*, Xin Du, MD48*, Yonghuai Feng, PhD49*, Yi Wang, MD50*, Ying Sun51*, Liye Zhong, MD, PhD52*, Li Gao53*, Wenming Chen, MD, PhD54*, Jian Li55* and Wen Gao, MD, PhD56

1Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
2Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
3Beijing Chao-Yang Hospital, Beijing, China
4The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, PR China, Zhengzhou, China
5Affiliated Hospital of Hebei University, Baoding City, Hebei Province, CHN
6Qilu Hospital of Shandong University, Jinan, China
7The Fifth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing, China
8Beijing Luhe Hospital, Capital Medical University, Beijing, China
9The First Hospital of Jilin University, Changchun, CHN
10Shanxi Cancer Hospital, Taiyuan, China
11The Second Hospital of Shanxi Medical University, Taiyuan, China
12The Affiliated Hospital of Nantong University,, Jiangsu, China
13Third Hospital of Peking University, Beijing, CHN
14China Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, China, China, China
15The Forth Hospital of Hebei Medical University, hebei, China
16Cangzhou Central Hospital, Cangzhou, CHN
17Department of Hematology, Shenzhen People’s Hospital, Rochester, MN
18Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China
19Beijing Jishuitan Hospital, Beijing,, Beijing, CHN
20Affiliated Hospital of Chengde Medical University, Chengde, China
21The Second Hospital of Hebe Medical University, Shijiazhuang, Hebei, China, Shijiazhuang, CHN
22The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
23Harbin Medical University, Shenyang, CHN
24Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, CHN
25the Second Affiliated Hospital of Nanchang University, Nanchang, CHN
26Central Hospital of Ordos, ORDOS, China
27The affiliated hospital of inner mongolia medical univuniversity, Hohhot, China
28The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
29Department of Hematology, Linfen People's Hospital, Linfen, China
30Shanxi Bethune Hospital, Shanxi, China, Taiyuan, CHN
31Heping Hospital Affiliated To Changzhi Medical College, Changzhi, China
32First Affiliated Hospital of Kunming Medical University, kunming, China
33Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, hangzhou, China
34The First Affiliated Hospital of Wenzhou Medical University, wenzhou, China
35The Fifth Affiliated Hospital Sun Yat-Sen University,, Zhuhai, CHN
36Department of Hematology-Oncology, Chongqing University Cancer Hospital, Chongqing, China
37Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China, Changsha, China
38Department of Hematology, Myeloma&Lymphoma Center, Shanghai Changzheng Hospital Navy Medical University, Shanghai, China
39The First Affiliated Hospital of Guangxi Medical University, Guangxi, China
40The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
41Shengjing Hospital of China Medical University, Shenyang, CHN
42The Second Hospital of Dalian Medical University, Dalian, China
43The First Affiliated Hospital of Dalian Medical University, Dalian, China
44The Third Affiliated Hospital of Hebei University, Shijiazhuang, CHN
45The Second Affiliated Hospital of Harbin Medical University, Harbin, CHN
46Bayannur Hospital, Inner Mongolia, China
47Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
48Division of Hematology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
49Department of Hematology, The Affiliated Hospital of Zunyi University, zunyi, China
50Shanxi Provincial People‘s Hospital, shanxi, China
51The Second Affiliated Hospital of Nanchang University, jiangxi, China
52Guangdong Provincial People's Hospital, Guangzhou, CHN
53The Xinqiao Hospital of Third Military Medical University, Chongqing 214426, China., China, China
54Department of Hematology, Beijing Chao-Yang Hospital of Capital Medical University, Beijing, China
55Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
56Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, CHN

Background Renal impairment (RI) is one of the cardinal features of newly diagnosed multiple myeloma (NDMM), contributing to dismal outcomes and high risk of early death. Improved renal function is associated with prolonged survival for NDMM. The triplet combination of pomalidomide with bortezomib and dexamethasone (PVD) has been proven to be effective in MM patients with RI[1] (The manuscript in preparation). However, the best renal overall response rate (ORR) was 78.8% and 21.2% of patients had no renal response to PVD.

Here we reported an interim analysis to evaluate the renal and hematologic response of SPVD (Selinexor, pomalidomide, bortezomib, dexamethasone) regimen as first-line therapy in NDMM with RI in this prospective, open-label, multicenter, phase 2 study (ChiCTR2200064695).

Methods Eligible NDMM with RI (defined as estimated glomerular filtration rate (eGFR) by MDRD < 40ml/min) were enrolled in the study. Sample size was designed to recruit 62 patients. RI caused by other reasons than tubular nephropathy was excluded. Patients received SPVD (Selinexor 40mg on days 1,8,15, pomalidomide 4mg on days1-14, bortezomib 1.3mg/m2 on days 1,4,8,11, and dexamethasone 20mg on day of and after bortezomib, 21days/cycle) for a maximum of 9 cycles. Autologous stem cell transplantation (ASCT) was administrated after 3 to 6 SPVD cycles for transplant-eligible patients. The primary endpoint was renal ORR at 3 months. Secondary endpoints included major renal response (≥partial response) at 3 months, hematological ORR, minimal residual disease (MRD), progression-free survival (PFS), overall survival (OS), and safety. The definition of both hematological response and renal response was according to the International Myeloma Working Group (IMWG) criteria.

Results Between Oct 28, 2022 and Jun 23, 2023, 31 patients were enrolled across 17 centers, with a median age of 61 years (range: 45-80). The proportion of R-ISS III was 35.5%. Median serum creatine level and eGFR were 365μmol/L [interquartile range (IQR): 214.5-508] and 14.5 mL/min (IQR: 10.5-22.64), respectively. There were 10/31 (32.3%) patients requiring dialysis at diagnosis and 8 patients with high-risk cytogenetic abnormalities [t(4;14), t(14;16), or del(17p)]. At the data cut-off date of July 11, 2023, the median number of SPVD treatment cycles was 3 (range: 1-8). The median follow-up time was 4 months. Two patients received first-line ASCT after induction therapy. The primary endpoint of renal ORR at 3 months was 74.2%, including 6.5% renal PR, and 25.8% renal CR (Table 1). The ORR of the best hematological response was 70.9% (45.1% ≥VGPR, 16.1% CR)(Table 1). The most common treatment emergent adverse events (TEAEs) (incidence >10%) were infection (45.2%), myelosuppression (45.2%), hepatic impairment (12.9%), nausea (12.9%), and hypokalemia (12.9%) (Table 2). Grade 3 or more hematologic toxicity was seen in 35.5% of the patients, the most common being thrombocytopenia (19.4%)(Table 2). Dose reduction or interruption of pomalidomide occurred in 5 patients due to myelosuppression and infection events. Three patients had dose reduction of selinexor due to nausea or vomiting. Notably, among non-hematologic toxicities, 4 patients developed hepatic impairment, and of those, one patient suffered tumor lysis syndrom, hepatic failure and severe infection and then died. Median PFS and OS were not reached.

Conclusion This study demonstrated SPVD is an effective combination in NDMM patients with RI. The toxicity profile was consistent with the reported research, but hepatic impairment during treatment should be noted with caution.


[1] JIAN Y, CHANG L, SHI M, et al. Renal Response of Pomalidomide with Bortezomib and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients with Renal Impairment: A Prospective, Open-Label, Multicenter, Phase 2 Study [J]. Blood, 2022, 140(Supplement 1): 10167-9. doi:10.1182/blood-2022-159361.

Disclosures: Fu: Takeda Pharmaceutical Company Limited.: Research Funding; Shanghai Changzheng Hospital: Other: WJF is a former staff of Shanghai Changzheng Hospital and now is a staff of Shanghai Fourth People's Hospital affiliated to Tongji University. .

*signifies non-member of ASH