Hodgkin lymphoma responds to immunotherapy

Patients with classical Hodgkin lymphoma whose cancer had failed to respond to other treatments showed improvement in studies that tested the effect of two PD-1 inhibitors - immunotherapy drugs that help the immune system recognize and attack cancer.

The immunotherapy drugs tested in the trials helped the Hodgkin lymphoma patients' immune system T-cells attack their blood cancer.

The results of the two phase 1 trials are being presented at the 56th Annual Meeting of the American Society of Hematology in San Francisco, CA.

The trial investigators - including members from Memorial Sloan Kettering Cancer Center (MSK) in New York, NY - also report one of the trials in the New England Journal of Medicine.

Lymphoma is a disease where white blood cells or lymphocytes become cancerous and grow uncontrollably. 

There are two main types of lymphoma - Hodgkin lymphoma and non-Hodgkin lymphoma, the latter being far more common.

The American Cancer Society estimates for the US suggest there will be nearly 9,200 new cases of Hodgkin lymphoma and about 1,180 deaths in 2014.

Classical Hodgkin lymphoma is the most common form of Hodgkin lymphoma.

The two studies tested the effects of two PD-1 inhibitors - pembrolizumab and nivolumab - in patients with classical Hodgkin lymphoma. PD-1 inhibitors are an example of immunotherapy - drugs that help the patient's immune system fight disease.

Trials show immunotherapy holds promise for treatment of blood disorders

PD-1 inhibitors are drugs that block PD-1, a protein on the surface of T-cells that deactivates the cells. T-cells are a type of lymphocyte or white blood cell that help the immune system recognize and eliminate cancer cells and other potentially damaging material.

Some cancer cells - like those in melanoma and Hodgkin lymphoma - escape attack from the immune system by switching on PD-1 on T-cells - effectively sending these soldiers of the immune system to sleep. PD-1 inhibitors wake them up again so they can keep fighting the cancer cells.

The pembrolizumab trial found that 66% of the Hodgkin lymphoma patients who received the PD-1 inhibitor had a complete or partial response. In the trial that tested the other PD-1 inhibitor nivolumab, patients showed similar positive results.

The investigators believe the findings show immunotherapy - a relatively new approach to fighting cancer - holds huge promise for the treatment of Hodgkin lymphoma and a range of other blood disorders.

These results are quite extraordinary given the dire circumstances these patients were facing. Pembrolizumab has already been approved for patients with advanced melanoma and we're excited that the drug is producing responses in other cancer types.

Both PD-1 inhibitors showed promising results in classical Hodgkin lymphoma

For the pembrolizumab trial, the investigators enrolled 29 classical Hodgkin lymphoma patients whose cancer had not responded to treatment with brentuximab vedotin. Twenty of the patients had also relapsed after stem cell treatment.

After 12 weeks, six of the patients (21% of the group) showed a complete response and 13 patients (45%) showed partial remission.

The investigators say no serious side effects were reported and only one patient stopped having treatment after experiencing a moderate adverse effect.

In the second study, investigators enrolled 23 classical Hodgkin lymphoma patients whose cancer had not responded to treatment - including 18 who had also relapsed after stem cell treatment - and gave them nivolumab.

After 24 weeks, four patients (17% of the group) had a completed response and 16 (70%) had a partial remission. Three serious side effects were reported.

"These data are the first to be reported for a completed study of a PD-1 inhibitor in classical Hodgkin lymphoma. This is good news for Hodgkin lymphoma patients and for the advancement of immunotherapies."

The Food and Drug Administration has given nivolumab Breakthrough Therapy Designation in relapsed cHL as a result of these findings.

The teams are now planning further trials to test the drugs in larger groups of patients.

References:

1. PD-1 blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE-013), Craig H. Moskowitz, et al., presented at 56th American Society of Hematology Meeting, published online 6 December 2014, meeting abstract 290.
2. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma, Stephen M. Ansell, et al., NEJM, doi:10.1056/NEJMoa1411087, published online 6 December 2014, abstract.
3. Memorial Sloan Kettering Cancer Center news release accessed 7 December 2014.