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PD-1 inhibitors shine at ASH conference

New data suggests the immunotherapy class could be also used for haematological cancers
merck keytruda

The progress of the PD-1 inhibitor class in oncology continues apace, with new data suggesting they will add haematological cancers to the tally of diseases they can tackle.

Delegates at the American Society of Haematology (ASH) annual meeting said over the weekend that Merck & Co's Keytruda (pembrolizumab) and Bristol-Myers Squibb's Opdivo (nivolumab) have both shown efficacy in Hodgkin's lymphoma, a disease which accounts for around 7% of all haematological malignancies.

Hodgkin's lymphoma is one of the most common cancers in young adults, though it can occur in teenagers and older patients. Most are cured by moderately intensive chemotherapy or radiotherapy, although in a small proportion of patients the cancer is resistant to treatment.

At the ASH meeting, Merck reported the results of a phase I trial involving 29 heavily-pre-treated Hodgkin's lymphoma patients who had failed therapy with Seattle Genetics' Adcetris (brentuximab vedotin) and - in some cases - stem cell transplant.

After treatment with Keytruda every two weeks for up to two years, six patients (21%) went into complete remission, with another 13 patients (45%) achieving a partial remission.

Similarly, a 23-patient, phase I trial of bi-weekly Opdivo found an overall response rate of 87%, with complete remission seen in four patients (17%) and a partial response observed in another 16 (70%).

Once again, most patients in the trial had seen their lymphoma progress despite earlier treatment with Adcetris and stem cell transplant, according to the study, which has been published in the New England Journal of Medicine.

The lead investigator in the Keytruda study - Craig Moskowitz of Memorial Sloan Kettering Cancer Center in New York - said the data were compelling given that for many of the patients "this was their last chance."

"It will be important to further evaluate this drug in combination with others, or perhaps even as a maintenance treatment, to enhance the post-transplant immune response," he said.

Meanwhile, Philippe Armand of the Dana-Farber Cancer Institute in Boston said the Opdivo results "validate the scientific hypothesis that Hodgkin lymphoma relies heavily on the PD-1 pathway for survival."

An editorial accompanying the nivolumab study in the NEJM by Mario Sznol and Dan Longo notes that the response rate seen in the trial was "remarkably high" and suggest "a future in which anti–PD-1 therapy will become the foundation for the treatment of Hodgkin's lymphoma, possibly sparing patients both short and long-term toxic effects of combination chemotherapy."

Opdivo and Keytruda have already been approved to treat melanoma and have also shown efficacy in late-stage trials involving patients with non-small cell lung cancer (NSCLC), as well as earlier-stage studies in a range of other solid tumour types.

The new results suggest their action as immune checkpoint blockade agents could also be an effective approach for blood cancers. AstraZeneca (AZ) is looking in that direction with its anti-PD-1 candidate MEDI4736, which is being tested alongside Johnson & Johnson (J&J) and Pharmacyclics' Imbruvica (ibrutinib) in haematological cancers including diffuse large B-cell lymphoma and follicular lymphoma.

Article by
Phil Taylor

8th December 2014

From: Research

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