ASH 2016: Myeloma Patients With High c-MYC Expression May Fare Better on Ixazomib, Lenalidomide and Dex.
Posted: Nov 26, 2016
ASH 2016: Myeloma Patients With High c-MYC Expression May Fare Better on Ixazomib, Lenalidomide and Dex. image

In an abstract to be presented at the upcoming American Society of Hematology (ASH) conference in two weeks, Dr. Philippe Moreau and colleagues show that patients with high c-MYC expression may fare better with ixazomib added to lenalidomide and dex than lenalidomide and dex alone. Ixazomib (Ninlaro), the first oral proteasome inhibitor  was approved by the FDA this time last year based on results from the phase III TOURMALINE-MM1 study. In the study, some patients did much better with the addition of ixazomib, so the researchers looked more deeply into the reasons why, looking at a cancer-causing gene called c-MYC. C-MYC increases cell proliferation, growth, protein translation, metabolism and cell death. Higher c-MYC expression is also related to myeloma progression.

The researchers performed whole RNA sequencing of CD138 cells using the Illumina Truseq test and matched the results to patient outcomes.
The RNA sequencing data was available for 59% of the patients; 213 had high c-MYC expression and 219 had low c-MYC expression. Patients who had received 2-3 therapies had higher c-MYC expression than patients having only received one prior therapy.
Both high and low c-MYC expression groups had similar progression free survival, but the only significant treatment effect of the triple combo was primarily seen in the high c-MYC group.
After a 15 month follow up, progression free survival was:
  • Patients with 1 prior therapy: 20.6 months (IRd) vs. 16.6 months (len/dex)
  • Patients with 2-3 prior therapies: Not reached (IRd) vs. 12.9 months (len/dex)

The study results show that in advanced myeloma, genetic alterations may be contributing to greater ixazomib sensitivity.

In an abstract to be presented at the upcoming American Society of Hematology (ASH) conference in two weeks, Dr. Philippe Moreau and colleagues show that patients with high c-MYC expression may fare better with ixazomib added to lenalidomide and dex than lenalidomide and dex alone. Ixazomib (Ninlaro), the first oral proteasome inhibitor  was approved by the FDA this time last year based on results from the phase III TOURMALINE-MM1 study. In the study, some patients did much better with the addition of ixazomib, so the researchers looked more deeply into the reasons why, looking at a cancer-causing gene called c-MYC. C-MYC increases cell proliferation, growth, protein translation, metabolism and cell death. Higher c-MYC expression is also related to myeloma progression.

The researchers performed whole RNA sequencing of CD138 cells using the Illumina Truseq test and matched the results to patient outcomes.
The RNA sequencing data was available for 59% of the patients; 213 had high c-MYC expression and 219 had low c-MYC expression. Patients who had received 2-3 therapies had higher c-MYC expression than patients having only received one prior therapy.
Both high and low c-MYC expression groups had similar progression free survival, but the only significant treatment effect of the triple combo was primarily seen in the high c-MYC group.
After a 15 month follow up, progression free survival was:
  • Patients with 1 prior therapy: 20.6 months (IRd) vs. 16.6 months (len/dex)
  • Patients with 2-3 prior therapies: Not reached (IRd) vs. 12.9 months (len/dex)

The study results show that in advanced myeloma, genetic alterations may be contributing to greater ixazomib sensitivity.

The author Jennifer Ahlstrom

about the author
Jennifer Ahlstrom

Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can contribute to cures by joining HealthTree Cure Hub and joining clinical research. Founder and CEO of HealthTree Foundation.