Steps for solving the HPD mystery
“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”
Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.
“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”
Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.
Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.
The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.
“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.
“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.
Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.
He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.
“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
Current treatment decision-making
Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.
For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.
“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.
Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.
Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).
“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”
A version of this article first appeared on Medscape.com.