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

Gao, Wen

Oral and Poster Abstracts
653. Multiple Myeloma: Prospective Therapeutic Trials: Poster III

Research, Clinical Research, registries

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.

Reference

[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. .

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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