Immunotherapy More Effective in Treating Aggressive Lymphoma than Chemotherapy

Dr. Adrienne Phillips
Dr. Adrienne Phillips

According to findings from a recent clinical trial, people with relapsed or refractory adult T-cell leukemia-lymphoma (ATLL) may have a promising new treatment option. This new option is mogamulizumab, an immunotherapy that augments the immune system in its fight against this aggressive form of lymphoma. The lead author of the study is Dr. Adrienne Phillips, an assistant professor of medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and an oncologist with the Bone Marrow and Stem Cell Transplant Program at NewYork-Presbyterian/Weill Cornell Medical Center.

The findings of a small clinical trial demonstrate that the antibody drug mogamulizumab, known as moga, induces tumor responses in nearly 28 percent of patients with a fast-growing and difficult to treat blood cancer called relapsed or refractory adult T-cell leukemia-lymphoma (ATLL). These response rates appeared better than the standard chemotherapy comparison results in this study. The investigators say moga may represent a breakthrough in treating ATLL, for which there are currently no drugs approved in the United States to specifically treat the disease. Mogalizumab binds to CCR4 proteins on tumor cells, allowing the immune system to better target them.

“In order to treat an aggressive cancer such as ATLL, you have to think outside the box,” said Dr. Adrienne Phillips…”By working with international collaborators to conduct the largest randomized trial ever in relapsed or refractory forms of this devastating cancer, we have been able to demonstrate the benefits of an innovative, immune based treatment approach and have taken a large step forward in efforts to make this treatment option available for ATLL patients here.”

Dr. Phillip’s findings were presented during the annual meeting of the American Society for Clinical Oncology (ASCO) on June 5th in Chicago. You can read more about her finding’s here.

Mathematical Analysis of Drug Resistance in CLL

landau
Dan Avi Landau, M.D., Ph.D.

According to a recent study published in Nature Communications by Weill Cornell Medicine investigator Dr. Dan Avi Landau the rate at which genetically mutated cancer cells grow could be a key to explaining why some CLL patients develop resistance to treatment. Dr. Landau’s findings demonstrate how an individual’s cell mutations can influence that individual’s response to treatment, leading to the development of resistance to treatments like ibrutinib. CLL patients who are treatment resistant require treatment strategies that take account of their treatment resistance. Using mathematical modeling researchers investigated how:

 “…some patients with chronic lymphocytic leukemia (CLL)…become resistant to the drug ibrutinib, which is used to treat the disease once other chemotherapy drugs have failed. They performed mathematical modeling of the growth rates of the sensitive and resistant cells, and discovered that a small cluster of cancer cells survived ibrutinib therapy due to a genetic mutation that was present prior to treatment, allowing these ibrutinib-resistant cells to multiply and the disease to progress unabated. The findings could offer scientists a framework to guide the development of combination therapies that overcome drug resistance in CLL and in other cancers.”

These findings could potentially allow for physicians to develop more precise treatment plans for patients. In theory physicians could be more easily able to treat their patients not just for their present conditions, but also take into account their future conditions.

Nivolumab Granted Accelerated Approval for the Treatment of Classical Non-Hodgkin Lymphoma

The Backstory

On May 14, 2014, the immunotherapy drug nivolumab (Opidivo) received the FDA Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma whose disease relapsed after autologous stem cell transplant and treatment with brentuximab vedotin. Almost exactly two years later, on May 17, 2016, the FDA granted nivolumab accelerated approval for the treatment of people with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin

What is nivolumab?

Nivolumab is the first PD-1 blocking antibody approved for the treatment of a hematologic malignancy. Nivolumab inhibits a protein called PD-1. PD-1 primarily functions as an immune checkpoint, reducing the body’s natural immune response. PD-1 blockers like nivolumab interfere with PD-1 function and allow a person’s own immune system to destroy cancer cells; i.e., PD-1 blockers help the immune system to kill cancer.

Why did the FDA grant nivolumab the accelerated approval designation?

Nivolumab was granted an accelerated approval by the FDA based on results from two clinical trials in adults with relapsed or refractory Hodgkin lymphoma. In one study of 95 patients that had previously undergone autologous stem cell transplantation and brentuximab vedotin, 65% of people responded to nivolumab, with this response lasting almost 9 months on average. The FDA evaluated the safety of nivolumab in 263 patients treated on the second study. As is the case with all accelerated approvals, continued approval will be contingent upon the confirmed clinical results of a randomized phase III trial.

Were there any side effects?

Immune-mediated side effects occurred in 1% to 5% of patients and included rash, pneumonitis (inflammation of the lung), hepatitis (inflammation of the liver), hyperthyroidism, and colitis (inflammation of the intestine). Serious side effects were reported by 21% of patients. Additionally, the FDA issued a “Warning and Precaution” notice for patients who receive nivolumab followed by an allogeneic stem cell transplant. This was due to an increase in complications after allogeneic transplant that may be related to nivolumab. The FDA advises health care professionals to closely follow patients who receive nivolumab followed by allogeneic stem cell transplant for any complications. They have also required further study on the safety of allogeneic HSCT after nivolumab by the drug sponsor.

How can you access nivolumab now?

As an FDA approved drug, nivolumab can be prescribed by any qualified health care professional.

In addition to standard clinical use, at Weill Cornell Medicine we are continuing to study nivolumab and other immunotherapy drugs. For more information about nivolumab or immunotherapy drugs in general, please contact us at 212-746-2919 to make an appointment or with any questions regarding clinical trials or sign up for our newsletter.