ATG-010 Plus Low-Dose Dexamethasone (Sd) in Chinese Relapsed/Refractory Multiple Myeloma (RRMM) Patients Previously Received Chimeric Antigen Receptor T-Cell (CAR-T)
Authors: Fu Weijun , Qiu Lugui , Xia Zhongjun , Fu Zhengzheng , Chen Wenming , Chang Chunkang , Fang Baijun , An Gang , Wei Yongqiang , Cai Zhen , Gao Sujun , Weng Jianyu , Chen Lijuan , Jing Hongmei , Fei Li , Liu Zhuogang , Chen Xiequn , Liu Jing , Yu Yang , Wang Aihua , Yu Zhinuan , Yang Yijun , Lynch Kevin 
Published: November 2021

Abstract
Background:
There are limited treatment options for multiple myeloma (MM) patients who have a disease progression after CAR-T therapy. ATG-010 (selinexor) is a novel, oral selective inhibitor of nuclear export, inhibiting exportin 1. US FDA has approved selinexor plus low dose dexamethasone (Sd) to treat patients (pts) with penta-refractory MM. MARCH study, a single arm, Phase 2, registrational study evaluating Sd in Chinese RRMM pts, achieved an overall response rate (ORR) of 29.3% (95% CI: 19.7, 40.4), rejecting the null hypothesis of the study. Given its unique and novel mechanism of action, Sd preserves anti-tumor activity regardless of specific prior therapies. In the MARCH study, encouraging activity was demonstrated in a small group of Chinese RRMM pts previously exposed to CAR-T therapy.
Methods:
The study enrolled 82 pts previously exposed and refractory to a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and last line of therapy. Among them, 10 had received lymphodepleting conditioning followed by CAR-T cell therapy before study screening. ATG-010 (80mg) plus dexamethasone (20mg) was administered orally twice weekly. Response was assessed by an independent review committee.
Results:
Among 10 pts, 8 were male and 2 were female. Median age was 58.5 years. Median duration from MM initial diagnosis was 5.2 years. A total of 6 pts (60.0%) had high-risk cytogenetic abnormalities, including 4 pts (40.0%) with del (17p). Three pts had baseline plasmacytoma. Five pts (50%) experienced very rapid disease progression as indicated by a median of 46.2% increase of tumor burden from screening to Cycle 1 Day 1. Patients were heavily pre-treated with a median of 9.5 prior regimens (range: 5-12), with 8 receiving more than 6 regimens. Four pts were exposed to daratumumab (triple-class exposure). ORR was 50% including 1 very good partial response and 4 partial responses. Disease control rate defined as SD and above was 70%. Median duration of response was 1.4 months (mo) (95% CI: 0.96, NE). Median progression free survival was 1.9 mo (95% CI: 0.93, 3.74). xx pts (xx%) pts died; median overall survival was not reached, and estimated 12-mo OS rate was 68.6%.
Adverse events were consistent with those events previously reported with Sd regimen in RRMM patients. The most common grade≥3 treatment emergent adverse events (TEAEs) included anemia, thrombocytopenia, neutropenia and nausea. Most events were manageable with appropriate supportive care or dose modification. Four pts (40%) experienced TESAEs, including anemia, pneumonia, neutropenia, and upper gastrointestinal hemorrhage. There were no TEAEs leading to treatment discontinuation or death.
Conclusions:
Sd was able to induce an encouraging response with a manageable safety profile for a group of Chinese RRMM patients desperately needing treatment after failing CAR-T therapy. With the small sample size, further investigation is warranted, including using ATG-010 in combination with other anti-MM therapies to potentially enhance and prolong therapeutic benefit.

Disclosures
Yu: Antengene Therapeutics Ltd.: Current Employment. Wang: Antengene Therapeutics Ltd.: Current Employment. Yu: Antengene Therapeutics Ltd.: Current Employment. Yang: Antengene Therapeutics Ltd.: Current Employment. Lynch: Antengene Therapeutics Ltd.: Current Employment.