Combining two treatment strategies for the treatment of B-cell lymphoma may be more effective than either strategy alone, according to a study published in Cell Reports (February 28, 2017;18[9]:2162-2174).
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The bromodomain and extraterminal (BET) family proteins act as inhibitors to switch off cancer-causing genes expressed within tumor cells. International clinical trials are in the process of assessing the use of BET-inhibitors for the treatment of blood cancers with a focus on the direct effects of the drugs in inducing cancer cell apoptosis and resistance development. However, the maximal therapeutic effects of BET-inhibitors in B-cell lymphoma require a strong host immune system, which suggests that immunotherapy may have a critical role in maximizing treatment.
Simon J Hogg, PhD, department of oncology, Peter MacCallum Cancer Center (Melbourne, Australia), and colleagues conducted a study to assess the efficacy of combining epigenetic and immune-based treatments for B-cell lymphoma. Investigators compared the effects of BET-inhibitors in immune-competent mice with immune-deficient mice.
Researchers found that the immune-competent mice with B-cell lymphoma had a far greater response to BET-inhibitors than immune-deficient mice. Additionally, BET-inhibitors were shown to switch off the programmed death-ligand 1 (PD-L1) pathway, which is used by tumor cells to evade the immune system.
Subsequently, immune-targeting drugs pembrolizumab and nivolumab, which are designed to target the PD-L1 pathway, were tested in combination with BET-inhibitors for efficacy and compared with BET-inhibitors or immune therapies alone. These tests later confirmed that combining BET-inhibitors with other immune therapies are more effective in treating B-cell lymphoma compared with either therapy alone.
“Our data provide compelling evidence for a functional interaction between [BET-inhibitors] and the host immune system that can be therapeutically exploited to mediate robust and prolonged anti-tumor responses,” authors of the study wrote.
Further research is being conducted to assess the efficacy of the cyclin-dependent kinase- (CDK) inhibitor dinaciclib in combination with pembrolizumab in relapsed lymphoma, myeloma, and chronic lymphocytic leukemia. Results are likely to lead to additional trials examining the combination therapy. – Zachary Bessette
