Immunotherapy Targeting Immune Checkpoint Inhibitor with Durvalumab for the Treatment of Relapsed/Refractory Lymphoma or CLL

Picture2By Jia Ruan, M.D., Ph.D.

A functional immune system is vital to control the growth of many types of cancers. Tumors can grow when tumor cells evade the immune system by modulating the tumor microenvironment through expression of inhibitory molecules such as PD-1 and PD-L1. Interaction of PD-1 receptor on T-cells with its ligand PD-L1 on tumor cells leads to T-cell exhaustion, immune dysfunction, and tumor progression. Recently therapeutic targeting of inhibitory checkpoint molecules like PD-1 and PD-L1 have shown promise as effective immunotherapy across a number of tumor types including solid tumors and lymphomas. These immunotherapies work by augmenting the patient’s immune system. The first generation of these new inhibitors include anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab, which have gained FDA approval for the treatment of melanoma and non-small cell lung cancer.

Durvalumab, also known as MEDI4736, is a human immunoglobulin (Ig) G1к monoclonal antibody (mAb) that selectively binds to human PD-L1 with high affinity and blocks its ability to bind to programmed cell death-1 (PD-1) receptor on the T-cells. As a PD-L1 inhibitor, durvalumab activates the tumor-infiltrating T-cells, allowing them to destroy the tumor cells. Essentially durvalumab acts a catalyst to reactivate the body’s immune system and destroy cancerous tumor cells.

Clinical Trial Summary 

Weill Cornell Medicine has recently opened a clinical trial for patients with relapsed/refractory lymphoma or released/refractory chronic lymphocytic leukemia (CLL) previously treated with at least one systemic therapy. The purpose of this study is to test the safety and effectiveness of durvalumab, a monoclonal antibody against PD-L1, in combination with other specific anti-lymphoma therapies, including lenalidomide plus rituximab, ibrutinib, and bendamustine plus rituximab.

The study will consist of 3 parts: dose finding, dose confirmation, and dose expansion.  Four treatment arms will be investigated:

-Arm A (durvalumab plus lenalidomide and rituximab);

-Arm B (durvalumab plus ibrutinib);

-Arm C (durvalumab plus bendamustine and rituximab);

-Arm D (durvalumab monotherapy).

Study subjects will receive treatment for approximately one year and be in follow-up for anywhere from two to five years after treatment.



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