Promising Activity Shown With Selinexor of Patients With R/R Multiple Myeloma

An encouraging overall response rate (ORR) was demonstrated in the MARCH study in patients with relapsed/refractory multiple myeloma (MM) given selinexor (Xpovio), according to Antengene Corporation.¹

Findings showed an ORR of 29.3% (95% CI, 19.7-40.4) with a median duration of response (DOR) of 4.7 months for all treated patients. Consistent responses throughout all risk groups, including patients who received prior "triple-class" and chimeric antigen receptor (CAR) T therapies or had cytogenetic abnormalities were also demonstrated.

"The MARCH study was the cornerstone of the accelerated approval for selinexor for R/R MM in China, confirming the results from the [United States] STORM trial. As Antengene is ready to launch selinexor in the second quarter of this year, we are very pleased to publish and share a full summary of the results of this pivotal trial with the medical community," said Kevin Lynch, MD, chief medical officer of Antengene. Corporation, in the press release. "Antengene is very excited to bring this new therapeutic option for R/R MM to improve the care of patients in China."

Based on results from the the global, phase 2 STORM study, the MARCH study examined selinexor combined with low dose dexamethasone for heavily pretreated patients with relapsed/refractory MM.

The single-arm, open-label study took place across 17 sites in China and enrolled 82 patients who were refractory to prior therapies with an immunomodulatory agent (IMiD), as well as a proteasome inhibitor (PI).² The median age of the enrolled patients was 60 years.

Of the total patients included in the trial, 55 (67.1%) had high-risk cytogenetic abnormalities and 18 patients (22.0%) had abnormal renal function. Enrolled patients were heavily pre-treated, having received a median prior regimen of 5. All 82 patients were refractory to both PI and IMiD, including 20 patients (24.4%) categorized as triple-class refractory population. Ten patients (12.2%) had undergone CAR T therapy.

Selinexor was administered orally to patients at 80 mg combined with dexamethasone at 20 mg on day 1 and day 3 of each week in 4-week cycles.

The primary end point was ORR per an independent review committee, with the null hypothesis of ≤15%. Secondary end points included assessment of DOR, progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetic (PK) profile.

Results of the study revealed that of patients who had triple-class refractory disease, the ORR was reported to be 25.0% (95% CI, 8.7-49.1). Patients who had received prior CAR T demonstrated an ORR of 50.0% (95% CI, 18.7-81.3) and those with high-risk cytogenetic abnormalities had an ORR of 25.5%.

Median PFS and OS were reported to be 3.7 months and 13.2 months, respectively. Efficacy was consistent across various subgroups and no significant drug accumulation was shown following multiple administrations. Additionally, no human PK ethnicity difference was identified between Chinese and western patients.

Of the adverse events (AEs) reported in the study, each was expected and manageable with supportive care and dose modification. The most frequent grade 3 and 4 AEs included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.2%), hyponatremia (29.3%) and lung infection (26.8%). Serious AEs were reported in 54.9% of patients.

REFERENCES:

1. Antengene's pivotal "MARCH" study to evaluate selinexor (ATG-010) in relapsed or refractory multiple myeloma published in BMC medicine. Antegene Corporation Limited. April 6, 2022. Accessed April 7, 2022. https://prn.to/3KoEGiI
2. Qui L, Xia Z, Fu C et al. Selinexor plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma previously treated with an immunomodulatory agent and a proteasome inhibitor (MARCH): a phase II, single-arm study. BMC Med. 2022.;20(1):108. doi: 10.1186/s12916-022-02305-4