Lymphoma Patients Respond to Pembrolizumab After Other Therapies Fail, Small Study Indicates

Lymphoma Patients Respond to Pembrolizumab After Other Therapies Fail, Small Study Indicates

Patients with NK-cell or T-cell lymphomas whose previous treatments failed showed remarkably good responses to the immunotherapy Keytruda (pembrolizumab) in a small trial.

The study, “PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase, indicated that the treatment could be an option for patients who had failed to respond to treatment. The report was published in the journal Blood.

Those with NK or T-cell lymphomas who fail to respond to a collection of therapies known as SMILE — for dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide — have had no other treatments to turn to.

Since these types of lymphomas are caused by the Epstein-Barr virus (EBV) — which triggers the expression of the checkpoint molecule PD-1 ligand — researchers at Queen Mary Hospital in Hong Kong figured that a PD-1 blocker might offer a new treatment approach.

They gave seven men with NK- and T-cell lymphomas, all of whom had failed to respond to L-asparaginase-containing treatments, the checkpoint inhibitor pembrolizumab. The therapy is approved under the brand name Keytruda for lung cancer, melanoma, and head and neck cancers.

All of the patients responded to the pembrolizumab treatment. Researchers assessed response by clinical examinations, imaging, microscopic tissue analysis, and measurements of virus and cancer DNA in the blood.

Two patients achieved a complete response on all parameters included in the study. Three more had no signs of cancer when examined by imaging and clinical methods. The last two had a partial response, with no virus left in the circulation, but cancer RNA was detected at tumor sites.

As this RNA later disappeared in one of the patients, researchers argued that the patients may have shown what is known as pseudo-progression — a state that looks like a treatment failure but is only a slower type of response. One patient died after two months because of a bleeding gastric ulcer. After a median follow-up time of six months, five of the patients were still in complete remission.

The only adverse event seen during the trial was a moderately severe rash, caused by an immune reaction. The side-effect could, however, be managed with corticosteroids and the man continued the pembrolizumab treatment.