Hyperprogressive Disease: A Potential Effect of Immunotherapy

Many people living with skin cancer have received immunotherapy treatment, or may receive it at some point in their lives. This course of treatment aims to stop the spread of cancer by destroying cancer cells in the body. Immunotherapy is different from chemotherapy which is used to fight cancer but also kills good immune system cells in the process. However, since the rise of immunotherapy, chemotherapy is used less as a course of treatment for patients with melanoma.1 With the new era of immunotherapy and the promising results it has for treating skin cancer, it still has a few risks. According to new research, hyperprogressive disease may be a potential effect of immunotherapy.2

Immunotherapy and melanoma

Immunotherapy along with targeted therapies is now commonly used in patients with metastatic melanoma and Merkel cell carcinoma.1 These immune checkpoint inhibitors (ICI’s) have shown great promise in the skin cancer community where survival rates have increased for those with late-stage melanoma.1 Immunotherapy, like other treatments, is meant to improve skin cancer outcomes and stop the spread of cancer. However, clinical trial results have shown there is a small percentage of people who actually encounter worsened symptoms after receiving immunotherapy treatment. This has been linked to the acceleration of the cancer progression known as hyperprogressive disease.2

What is hyperprogressive disease?

Hyperprogressive disease (HPD) is a new phenomenon that has been linked to patients that have received immunotherapy. HPD is the sudden acceleration of tumor growth after the use of immune checkpoint inhibitors (ICI’s). Research is currently underway to understand if the rapid tumor growth is caused by immunotherapy or by a failure of antitumor efficacy.3

In the largest research study to date, Ferrera and colleagues compared the prevalence of HPD in lung cancer patients receiving immunotherapy vs chemotherapy. Results from this study showed that 14% of patients that received immunotherapy ended up with HPD and had “significantly worse overall survival in those with HPD compared to those with slower rates of progression (3.4 months vs 6.2 months)."3 Across all other studies, the incidence of HPD among those using immunotherapy treatment ranges from 10–30%.2 These studies are typical of smaller sample sizes, and HPD, being so new, may create differences in the definitions. Hopefully, in the near future, more research on HPD and skin cancer will be conducted.

As of right now, there have been mixed reviews on what variables impact hyperprogressive disease. One study of a small cohort found that twelve patients (7% of the research participants) had HPD, and ten of those participants were female.2 However, this needs to be validated in a larger cohort study.

Closing remarks

There still seems to be some inconsistencies between research studies and if hyperprogressive disease truly stems from receiving immunotherapy, but it is a phenomenon that should not be ignored. HPD may not necessarily be exclusive to immunotherapy, but from studies, HPD seems to be much more prevalent in patients receiving this form of treatment. Hopefully, throughout the next decade or so, larger cohorts can be used so more information on HPD will come to light.

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