Tag: Hodgkin Lymphoma

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.

Pembrolizumab Granted FDA Breakthrough Therapy Designation for Relapsed/Refractory Classical Non-Hodgkin Lymphoma

The Backstory

On April 18 the FDA granted the immunotherapy pembrolizumab (Keytruda) the Breakthrough Therapy Designation for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma (cHL). The Breakthrough Therapy Designation indicates that the FDA perceives the drug candidate may represent a substantial improvement over existing therapies and that it warrants additional resources to help expedite the approval process.

What is pembrolizumab?

Pembrolizumab is a humanized monoclonal antibody that binds to programmed death receptor-1 (PD-1). PD-1, also called programmed cell death protein-1, binds to programmed death ligand-1 (PD-L1), initiating inhibitory, immunosuppressive signals in T cells. Tumor cells, like Hodgkin lymphoma cells, often take advantage of this PD-1 by increasing expression of PD-L1, turning off the T cells and helping them to evade a potentially damaging immune response. Pembrolizumab acts by binding to PD-1, blocking its inhibitory actions, thereby activating the T-cell response against cancer cells, and initiating cell death.  Pembrolizumab is already approved by the FDA for treatment of patients with unselectable or metastatic melanoma and for patients with non-small cell lung cancer whose tumors express PD-L1.

Why did the FDA grant pembrolizumab a Breakthrough Therapy Designation?

The new designation is based on preliminary date from the KEYNOTE-013 trial, which was last presented at the 2015 meeting of the American Society of Hematology, and the KEYNOTE-087 trial. In KEYNOTE-013, 64% of patients with brentuximab vedotin-refractory cHL responded, including 16% achieving a complete response. Results from the KEYNOTE-087 trial are not yet public but will likely be presented soon.

Were there any side effects?

Side effects were considered manageable and the most common included hypothyroidism, diarrhea, nausea, and pneumonitis.

How can you access pembrolizumab now?

Although the FDA has approved pembrolizumab for melanoma and lung cancer, it has not yet approved pembrolizumab for Hodgkin lymphoma. Patients interested in receiving immune checkpoint inhibitors are advised to seek out clinical trial options. Please visit our clinical trials website or contact our office (646-962-2064) for additional information.

Dr. John Leonard Comments on the Use of Brentuximab Vedotin as a Monotherapy for Elderly Hodgkin Lymphoma Patients

The Oncology Times reported on results from a small prospective, Phase II open label study published in Blood, that found brentuximab vedotin may be of use for elderly Hodgkin lymphoma patients, who cannot tolerate harsher chemotherapy treatment options. From the 19 patients the objective response rate was 92% with 73% of patients achieving a complete response rate and 19% a partial remission rate. First author, Dr. Andres-Forero-Torres MD reported:

“We took patients who were older than 60 and not candidates for chemotherapy due to comorbidities or who did not want to receive chemotherapy, and we treated them with brentuximab vedotin as a single agent…We were able to show in this small but significant population of patients that older patients tolerated brentuximab vendotin very nicely. We found very high rates of response–almost everybody had a response, and a very good percentage had a complete remission.”

Lymphoma Program Director, Dr. John Leonard commented on the results:

“The issue is that the standard therapies in elderly and frail patients do have significant toxicity, so trying to come up with something that has less toxicity, if it can also be effective, is valuable…Brentuximab vedotin has less toxicity against the lungs, which is an issue with bleomycin, and less in the way of low blood count which you have in standard chemotherapy. It also avoids the cardiac toxicity of standard treatment as well.

Currently there are two trials comparing brentuximab vedotin to other treatment regimens open at Weill Cornell Medicine. The first trial is open to patients with advanced classical Hodgkin lymphoma and the second trial is open to patients with CD-30-positive mature T-cell lymphomas.