A new drug recently approved for the treatment of patients with multiple myeloma is now being tested for its ability to fight central nervous system (CNS) lymphoma, a deadly cancer of the immune system that can affect the brain, spinal cord and fluid, and eyes. The disease carries a poor prognosis.
The clinical trial, now open at the three campuses of Mayo Clinic ? in Florida, Minnesotaand Arizona? follows successful testing of the drug, pomalidomide (Pomalyst?; Celgene) , in mouse models of CNS lymphoma. Details of the preclinical testing are available in the science journal PLOS ONE.[1]
Approximately 5,000 patients are diagnosed with the disease every year in the United States.
…Our preclinical study suggests pomalidomide is very promising treatment options and significantly improved the survival and suppressed the tumor growth…
In previous studies, the researchers noted that pomalidomidecrosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations further showed that the drug had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival. Another benefit observed by the researchers was thatpomalidomidehad a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status.
Potential benefit for patients
Commenting on the importance of these results and what they mean for patients,Han Tun, M.D., an oncologist at Mayo Clinic in Florida, explained:”We believe pomalidomide could be beneficial in patients with this cancer because it does two things that most anti-cancer drugs do not do. The drug has excellent brain penetration, which is a requirement in treatment of brain tumors. The other interesting thing is that it is not only active directly against lymphoma cells but also alters the tumor microenvironment.”
Tun is the principal investigator for the clinical trial, which is accruing patients, and one of the authors of the study published in PLOS ONE. “Our preclinical study suggests pomalidomide is very promising. Treatment with pomalidomide in mouse models for CNS lymphoma significantly improved the survival and suppressed the tumor growth,” he says. “The phase I clinical trial was developed based on these preclinical results.”
Pomalidomide belongs to a class of drugs called immunomodulatory agents.[3] Thalidomide was the first drug in this class and was approved in 2006 for treatment of multiple myeloma, a bone marrow cancer. Pomalidomide was approved for use in multiple myeloma in February.
For more information:
[1] NCT01722305 – Study of Pomalidomide for Treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma and Newly Diagnosed or Relapsed/Refractory Intraocular Lymphoma [Clinical Trial]
[2] Li Z, Qiu Y, Personett D, Huang P, Edenfield B, et al. (2013) Pomalidomide Shows Significant Therapeutic Activity against CNS Lymphoma with a Major Impact on the Tumor Microenvironment in Murine Models. PLoS ONE 8(8): e71754. doi:10.1371/journal.pone.0071754 [Article]
[3] Highlights of Prescribing Information Pomalyst? (pomalidomide) capsules, for oral use Initial US Approval: 2013.[Prescribing Information]
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