By Paul Kleutghen | Posted - Feb 4th, 2021





Interfering with a Specific Gene (IRF4) to Treat Multiple Myeloma

Researchers reported a few years ago that the gene ‘interferon regulatory factor 4’ (IRF4) is primarily expressed in the bone marrow of myeloma patients. IRF4 allows myeloma stem cells to proliferate and survive and higher levels of IRF4 are associated with a lower overall survival prognosis. At the time, the same team postulated that IRF4 could be a possible target for the development of myeloma immunotherapy. 

Turn the clock forward to today. A recent article in the Journal ‘Cell Stem Cell’ provides a progress update on targeting IRF4 to treat myeloma. A collaborative effort between the University of San Diego Medical School and Ionis Pharmaceuticals has resulted in the identification of a compound that inhibits IRF4. This medicine, currently named ION251, is an engineered piece of DNA that is specifically designed to ‘tie-up’ the genetic material coding in IRF4 causing it to degrade. 

Preclinical studies have shown that ION251 lowered disease burden, reduced myeloma stem cell abundance, and increased survival of mice bearing human myeloma”. In addition, ION251 eradicates “myeloma progenitors and malignant plasma cells while sparing normal human hematopoietic stem cell development … and promotes sensitivity to myeloma drugs.”

A two-part Phase I study in humans to study this drug has been approved by FDA and Ionis is currently recruiting patients. The purpose of Part 1  is to determine the maximum-tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) will be studied of ION251 in patients with relapsed/refractory multiple myeloma. Study details (study sites, contact information, inclusion/exclusion criteria) can be found here.

This drug has progressed very rapidly from concept to proof of concept, through preclinical studies and now into human studies. Even though the outcomes in myeloma burdened mice were exciting (rapid reduction of myeloma cells after 2-6 weeks of treatment), it is still too early to speculate on this drug’s performance in humans. IF the results will be favorable then we will have gained another arrow in our future quiver of targeted myeloma treatments. Time will tell but let’s keep our fingers crossed in the meantime. 

Paul Kleutghen
About the Author

Paul Kleutghen - I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and a grandson who is the ‘light of my life’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs and, very specifically, CAR-T therapies, with recent contributions posted by Health affairs, the Institute for Clinical and Economic Review and the Centers for Medicare and Medicaid Services.


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