Tag: immunotherapy

New Immunotherapy Treatment Approved for Children and Adults with Hodgkin Lymphoma

On March 14, 2017, the Food and Drug Administration (FDA) approved pembrolizumab for the treatment of refractory Hodgkin lymphoma in children and adults who have been treated with at least three prior therapies.

Pembrolizumab is a type of immunotherapy called a checkpoint inhibitor. This drug consists of an antibody that binds to programmed death receptor-1 (PD-1), preventing the cancer cells from evading detection by the body’s immune system. Treatment with pembrolizumab allows T-cells (the fighter cells) to mount an immune response against the malignant cells.

Since 2014, Pembrolizumab has been FDA approved for the treatment of unresectable or metastatic melanoma, metastatic non-small-cell lung cancer, and recurrent or metastatic head and neck squamous cell carcinoma. The approval of pembrolizumab for the treatment of relapsed Hodgkin lymphoma was made under the FDA’s accelerated approval process.

This approval was based on data from a clinical trial of pembrolizumab in 210 adult patients with Hodgkin lymphoma who had relapsed or refractory disease after autologous stem cell transplant and/or treatment with brentuximab vedotin.  With a median follow up of 9.4 months, the overall response rate was 69%, including partial responses in 47% and complete responses in 22% of patients. The approval in pediatrics was based on known safety data and extrapolated efficacy based on the adult trial.

The most common adverse events in the trial were fatigue, fever, cough, musculoskeletal pain, diarrhea, and rash. Among 40 pediatric patients with advanced melanoma, PD-L1 positive tumors, or lymphoma, the side effects and overall safety profile was similar to adults.  A “warning and precaution” was added to the label describing the potential complications of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplant after treatment with pembrolizumab.  Death related to GVHD has occurred and physicians are advised to monitor for hepatic veno-occlusive disease and grade 3-4 acute GVHD including hyperacute GVHD.

The recommended dose of pembrolizumab for patients with Hodgkin lymphoma is 200mg every 3 weeks in adults and 2mg/kg (up to 200mg) every 3 weeks in children.

At the Weill Cornell and NewYork-Presbyterian Lymphoma Program, we offer pembrolizumab as one of many treatment choices available for people with Hodgkin lymphoma.

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.

Dr. John Leonard Discusses New Treatments for Follicular Lymphoma

OncLive recently reported on a presentation made by Lymphoma Program Director, Dr. John Leonard at the 2016 International Congress on Hematologic Malignancies on novel treatments that could improve the long term survival of patients with follicular lymphoma. In introducing this topic he noted,

“Most patients will not die from follicular lymphoma, and that’s very reassuring. About 80% of patients will die with their follicular lymphoma and not of their follicular lymphoma…That really tells you something. If 80% of patients are not going to die from their disease, we can make a patient feel a lot better and can guide how we treat the patient.”

The article than summarizes Dr. Leonard’s discussion of these potential new treatments. Some of these treatments for follicular lymphoma are currently being investigated in clinical trials at Weill Cornell Medicine. If you are interested in a trial for follicular lymphoma, please look to our Joint Clinical Trials listings.