By Paul Kleutghen | Posted - Jul 7th, 2021

 

 

 

 

Iberdomide: A Potent New Drug to Treat Revlimid/Pomalyst Resistant Myeloma

Most multiple myeloma patients will take Revlimid or Pomalyst at some point in their treatment, but many patients can become resistant to these immunomodulators (iMiDs) over time. A new drug is in development called iberdomide is now in development to provide better results with a lower side effect profile. It is similar to the iMiDs in some ways, but different in others. 

 

Iberdomide is a drug that comes from the Celgene development pipeline, acquired by Bristol Myers in 2019. The drug targets the protein Cereblon (also targeted by Thalomid, Revlimid and Pomalyst). Cereblon is part of a group of proteins strung together, knows as the  “Cul4ACRBN E3 ligase complex”. There is a good chance that we will hear much more about this protein complex in the next few years.

letter to the Editor of the  Journal Nature Leukemia was published shortly before the 2019 annual meeting of the American Society of Hematology that summarized preclinical (lab) studies of iberdomide. The conclusion of this summary indicated the potential of this compound:

“Overall, iberdomide biochemical potency translates into greater anti-multiple myeloma activity than lenalidomide [Revlimid] or pomalidomide [Pomalyst] in both IMiD-sensitive and -resistant MM cell lines. These results provide strong preclinical and translational evidence for iberdomide activity and its potential for clinical development in multiple myeloma in combination with other agents, especially with bortezomib and daratumumab in relapsed/refractory multiple myeloma.”

 

A complex Phase I/II clinical trial of 456 patients is currently ongoing and is still recruiting patients. I call this trial complex in that it tests several different combinations of iberdomide together with other drugs with well-established anti-myeloma activity. Those interested in learning more about this trial can do so by clicking on the following link (NCT02773030). The recommended safe and effective dose of iberdomide, given as a single agent or together with other drugs, has already been determined in the Phase I program.

An interim update of the efficacy of iberdomide dosed in combination with these other drugs was presented at the most recent meeting of the European Hematology Association. The results disclosed so far are summarized in the table below:

 

Drug Combination

Iber-Darzalex-dex

(IberDd)

Iber-Velcade-dex

(IberVd)

Iber-Kyprolis-dex

(IberKd)

# of patients evaluated so far

43

25

9

Median # of treatment cycles

4

6

5

Overall Response Rate (ORR)

45.9%

56.0%

50.0%

Median time to response (weeks)

4.1

3.6

4.1

Median Duration of Response (weeks)

35.7

Not yet reached

Not yet reached

Adverse events grade 3 or higher

 

 

 

Neutropenia

66.6%

28.0%

33.3%

Anemia

20.5%

 

 

Thrombocytopenia

 

24%

 

 

A couple of points may be worth noting:

  • These are VERY early results, especially when considering that the full clinical trial will encompass more than 400 patients. It is fairly safe to assume that Bristol-Myers will be reporting additional clinical progress as time goes on
  • Please be aware that the antiproliferative activity of iberdomide is greater than Pomalyst (and in turn, activity of Pomalyst is greater than Revlimid). This means that iberdomide will hopefully start filling the treatment gap that occurs when patients become resistant to either or both Revlimid and Pomalyst.
  • Also of interest is the fact that iberdomide induces greater cancer cell death compared to Pomalyst at only one tenth the concentration of Pomalyst.
  • Iberdomide is an oral agent, just like Revlimid/Pomalyst.

 

Iberdomide is a compound that is starting to become more interesting for us, myeloma patients, to follow in the future. The clinical program still has quite a bit more to go but let’s keep our fingers crossed that the drug will give us another treatment option when we may be hitting a tough stretch some years from now.

 
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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