Immunotherapy for Hodgkin lymphoma: breakthrough results

7 Dec 2014

Scientists report that 87% of Hodgkin lymphoma patients who participated in an early-phase immunotherapy clinical trial experienced cancer remission. The results provide evidence of the potential of therapies that help the immune system to kill cancer cells.

While clinical trials of such immunotherapies in other cancers have shown them to be highly effective in a subgroup of patients, the new study stands out because nearly all patients benefited from the treatment.

The success of the agent, nivolumab, in this study has prompted the U.S. Food and Drug Administration to designate it a "breakthrough therapy" for treating relapsed HL, and a large, multinational Phase 2 trial is now under way.

Details of the study involving 23 patients

The study involved 23 patients with relapsed or treatment-resistant Hodgkin Lymphoma, a cancer of white blood cells called lymphocytes. Although relatively uncommon, it is one of the most frequent cancers in children and young adults. While the disease can often be treated successfully with current therapies, up to a quarter of all patients eventually have a relapse.

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In the current study, almost 80% of the patients had undergone a previous stem cell transplant. More than a third had received at least 6 prior lines of therapy without lasting success.

The patients received biweekly infusions of nivolumab, which is an antibody that blocks a protein called PD-1 on the surface of immune system T cells. T cells are key actors in the body's defenses, identifying foreign or diseased cells and leading an assault on them. But when PD-1 binds to proteins called PD-L1 and PD-L2 on the surface of certain cancer cells, the T cells essentially become paralyzed: the immune attack on cancer is called off. By blocking PD-1, nivolumab allows the attack to proceed.

"This is a treatment that, rather than targeting cancer cells themselves, targets the immune response, reactivating the T cells in the neighborhood of the tumor cells," Shipp remarked.

Positive study results

Twenty of the 23 patients had a measurable response to the treatment, with four achieving a complete response -- in which no detectable tumor was left (and 16 having a partial response) in which their tumors shrank to less than half their original size. Six months after completing therapy, 86% of the patients were alive with continued responses. Most patients continue to do well a year after their treatment.

Side effects mirrored those that have occurred in tests of nivolumab in patients with solid tumors. About 20% experienced a serious treatment-related adverse effect but none was life-threatening.

Study author: "the kind of result that you get to see once in your career"

"What makes these results especially encouraging is that they were achieved in patients who had exhausted other treatment options," said the study's co-senior author, Margaret Shipp, MD, chief, Division of Hematologic Neoplasia at Dana-Farber. "We're also excited by the duration of responses to the drug: the majority of patients who had a response are still doing well more than a year after their treatment."

Although this was a relatively small, phase 1 trial, the investigators involved believe the results are compelling. "For someone like myself, in this kind of work, this is the kind of result that you get to see once in your career," said study co-senior author Philippe Armand, MD, PhD, medical oncologist in the Hematologic Oncology Treatment Center at Dana-Farber.

Source: Science Daily

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