Novel treatment options in lymphoma and leukemia 1

Hello everyone. My name is Nishitha Reddy and I'm the Associate Professor of Medicine at Vanderbilt University Medical Center and the Director of the Lymphoma Program here. Today we'll be discussing the novel treatment options that are available for lymphoma and leukemia treatments.

So in the last decade, we have seen an emergence of several new drugs that have been approved for both Hodgkin and non-Hodgkin lymphoma, and most of these agents are targeted therapies that were designed to alter a specific pathway or antibodies that bind to a particular site. As we can see here, several novel agents have been approved since 2008 up until now. Starting in 2008, bendamustine was approved for relapsed indolent lymphomas. And following that, several new agents have been approved specifically obinutuzumab, which is one of the novel monoclonal antibody therapies for approval in CLL and relapsed follicular lymphoma in combination with bendamustine. Another agent is brentuximab, which was approved in 2011 for Hodgkin lymphoma. And more recently some of the novel agents such as PD-1 inhibitors, specifically nivolumab and pembrolizumab have been given accelerated approval for Hodgkin lymphoma. So in the next several slides, we will be discussing the mechanisms of action of these agents, the current indications, the side effects of novel agents used in the treatment of lymphomas and leukemias.

Here's an example of several new drugs that are in the development of lymphoma for various indications. Although, this slide does not cover all the novel targeted drugs, it at least gives us an idea to where we stand in drug development, and how these agents will shape in the future of therapy for lymphoma. For, example, some of the newer monoclonal antibodies directed towards CD20 are obinutuzumab and ofatumumab. And brentuximab is a CD30 antibody which has been recently approved for Hodgkin lymphoma. We will go further in detail of these drugs as we move further into the slides. Proteasome inhibitors are specifically targeting the NFkB pathway, and one such drug is bortezomib, that's been approved for mantle cell lymphoma. Other second generation proteasome inhibitors are also currently under development such as carfilzomib and ixazomib. HDAC inhibitors which are histone deacetylase inhibitors, romidepsin, vorinostat, and belinostat have also been approved in T-cell lymphomas. Another exciting area are Burton's kinase inhibitors such as ibrutinib, and acalibrutinib. While discussing tyrosine kinase inhibitors, we would also like to mention PI3kinase inhibitors which specifically inhibit the PI3kinase pathway and the mTOR pathway are the idelalisib, duvelisib, and copanilisib. Currently, idelalisib is the drug that's approved for treatment in indolent non-Hodgkin lymphoma. More recently, BCL2 inhibitors have been gaining interest. Specifically, the BCL2 inhibit the BCL2 pathway, and an example in that area is venetoclax. Immune checkpoint inhibitors which are mostly of interest in solid tumor oncology such as lung cancer and melanoma have recently gained interest in lymphomas as well. Nivolumab, and pembrolizumab are such examples, they are PD1 and PDL1 inhibitors, specifically. Fostamatinib is a splenic tyrosine kinase inhibitor, and second generation splenic tyrosine kinase inhibitors are currently underway. Certain drugs that are called immune modulators which really don't have any specific single mechanism of action but have a varied mechanism of action and are also anti-angiogenic are lenalidomide, and pomalidomide approved in multiple myeloma but also seem to have activity in lymphomas as well.