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Shaji K. Kumar, MD

Prashant Kapoor, MD, FACP


Novel SK2 Inhibitor Under Study in Resistant Multiple Myeloma

By: Joseph Fanelli
Posted: Monday, March 6, 2023

For patients with relapsed or refractory multiple myeloma, the sphingosine kinase 2 (SK2) inhibitor opaganib may prove to be an innovative molecular target for antimyeloma therapy with potential activity, according to phase I trial findings presented in the journal Annals of Hematology. Yubin Kang, MD, of the Duke University Medical Center, Durham, North Carolina, and colleagues found that most patients treated were able to tolerate doses as high as 750 mg of opaganib over multiple cycles.

“This trial provides the first proof-of-concept data that targeting sphingolipid metabolism with a SK2 inhibitor, specifically opaganib, may be a useful approach toward the treatment of [relapsed or refractory multiple myeloma],” the authors concluded. “Because of their [sphingolipids] key role of phosphorylating sphingosine to S1P [ceramide:sphingosine-1-phosphate], sphingosine kinases are being increasingly recognized as important targets in cancer treatment and in immune modulation.”

In this study, the authors enrolled 13 patients with relapsed or refractory multiple myeloma who were previously treated with immunomodulatory agents and proteasome inhibitors. Three oral doses of single-agent opaganib were given twice daily; three patients received 250 mg, four patients received 500 mg, and six patients received 750 mg over 28-day cycles. Seven patients were male, and the median patient age was 68 years. The median number of prior lines of treatment was five.

The authors found that the most common possibly related adverse events were decreased neutrophil counts, and there were no reported serious adverse events related to the use of the drug. The investigators determined that the maximal tolerated dose was 750 mg twice daily.

On an intent-to-treat basis, one patient in the 500-mg dose cohort demonstrated a very good partial response, and one patient achieved stable disease for 3 months.

Disclosure: For full disclosures of the study authors, visit

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