Is the MDM2 Gene Associated with Hyperprogression Post Immunotherapy?


Oncology researchers worldwide closely watch MDM2 (mouse double minute 2 homolog), a gene involved in the amplification of tumor checkpoint inhibitor who showed hyperprogression had the gene.

What is Hyperprogression?

Hyperprogression refers to accelerated tumor growth in cancer patients post immune checkpoint inhibitor treatment. In some cases the size of the tumor could increase up to 40X its’ original size reports Kim Yun-mi of Korea Biomedical Review.

Immunotherapies Help and in some Cases Hurt

Leading immunotherapies include:

  • Keytruda (pembrolizumab)
  • Opdivo (nivolumab)
  • Tecentriq (atezolizumab)
  • Imfinzi (durvalumab)

They have raised anticipation for better efficacy such as higher survival rates in various types of cancers.   However, as much as they have positively impacted significant survival rates in various cancer types, the ration of early deaths because of hyperprogression has risen according to Korea Biomedical Review.

MDM2 Association with Hyperprogression

In March 2019, a University of California, San Diego Moores Cancer Center researcher, Razelle Kurzock, articulated that MDM2 amplification was “very strongly correlated with hyperprogression.”  Dr. Kurzock noticed that two patients she was working with in her San Diego clinic showed hyperprogression also had MDM2 amplification.  In a follow up video Dr. Kurzock noted that MDM2 only shows up in 4% to 5% of cancer patients.

First Affiliated Hospital of Nanchang University Study

The research team in a presentation titled “Developmental Immunotherapy and Tumor Immunobiology” will reveal the outcome of an important study: “Association between MDM2/MDM4 amplification and PD-1/PD-L1 inhibitors-related hyperprogression disease: a pan-cancer analysis.”

The Chinese researchers reviewed extensive clinical trials of PD-1/PD-L1 inhibitors in advance of solid tumor patients updated to January 2019, estimated the incidence of hyperprogressive disease (HPD), which was defined as time-to-treatment failure (TTF) less than two months, and more than 50% increase in tumor burden compared with pre-immunotherapy imaging.

The team secured the proportions of MDM2/MDM4 amplification across different cancer types from the Cancer Genome Atlas (TCGA) and their database at the hospital.

Their analysis included 19 published clinical trials of 1,318 patients treated with PD-1/PD-L1 inhibitors, covering 12 types of solid cancer.

The Results

The results evidenced that incidences of HPD ranged from 1.58% in RCC to 24.3% in sarcoma. Correspondingly, the proportions of MDM2/MDM4 amplification for these cancer types in TCGA were .75% in RCC to 20.38% ins sarcoma.

Their findings suggest that MDM2/MDM4 amplification could possibly be associated with rapid disease progression in PD-1/PD-L1 inhibitors among various types of tumors.