Checkpoint Inhibition for Non-Hodgkin and Hodgkin Lymphomas

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Most non-Hodgkin lymphomas do not display the same genetic alteration as classical Hodgkin lymphoma, and are much less susceptible to PD-1 blockade.
Most non-Hodgkin lymphomas do not display the same genetic alteration as classical Hodgkin lymphoma, and are much less susceptible to PD-1 blockade.

Classical Hodgkin lymphoma (cHL) has a cure rate of about 75% with standard chemotherapy. Its nearly universal genetic alterations, furthermore, likely contribute to its unique sensitivity to PD-1 blockade.

Most non-Hodgkin lymphomas (NHL) do not, however, have the same genetic alterations as cHL, and are consequently much less susceptible to PD-1 blockade. A newly published overview on checkpoint blockades in cHL and NHL elaborates on these differences.1

Merryman et al discussed the rationale and clinical applications of immune checkpoint blockade in cHL and NHL, noting that most cHL tumors display increased PD-L1 expression on the cell surface and on tumor-infiltrating macrophages.

Immunotherapeutics show “significant therapeutic success” in hematologic tumors, the authors said. cHL tumors are uniquely vulnerable to this particular checkpoint blockade, but even so, patients are likely to progress on these treatments.

“Optimizing checkpoint blockade in lymphoma is very unlikely to have a uniform answer,” the authors wrote. “The successes to date, both in the laboratory and in the clinic,” warrant further research on both the biological basis of checkpoint blockade in lymphoma and “judicious clinical testing of this strategy.”

“If you select the right patients, you can get high response rates using a checkpoint blockade strategy that really targets using the patient's own immune system. Patients can avoid more cytotoxic chemotherapy,” said Brad S. Kahl, MD, professor of medicine at Washington University School of Medicine in St Louis, Missouri. “For example, among lymphomas, checkpoint inhibitors are most profoundly active in Hodgkin lymphoma, where there's an underlying genetic basis for increased PD-1 ligand expression in these tumor cells.”

Not all lymphomas will respond equally well, Dr Kahl added, and “that's one of the points of this review article. The work that's been done so far in the NHL subtypes has shown that the activity of checkpoint inhibitors is much more modest. While the response rates are close to 70% in cHL, the response rates in the different NHL seem to be substantially less” — somewhere in the range of 20% to 30%.

“Right now, the activity of this type of immunotherapy is relatively modest in NHL — and there is no role outside of clinical trials,” Dr Kahl said. “In cHL, the single-agent activity of the checkpoint inhibitor is very high and incredibly promising. I think we're about to see a whole generation of studies testing the use of these agents as part of front-line management strategy in cHL by combining these agents with conventional chemotherapy.”

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