Scientists identify germline signature that predicts side effects from anti-PD1/PDL1 checkpoint therapy

Date:
February 3, 2022
Source:
University of California - Los Angeles Health Sciences
Summary:
Investigators have identified a germline biomarker signature that
successfully predicts which patients will suffer serious side
effects that occur in up to 3 in ten patients on anti-PD1/PDL1
therapy, a promising new approach to treating cancer.



FULL STORY ========================================================================== Investigators from UCLA Jonsson Comprehensive Cancer Center have
identified a germline biomarker signature that successfully predicts
which patients will suffer serious side effects that occur in up to 3
in ten patients on anti-PD1/ PDL1 therapy, a promising new approach to
treating cancer.


========================================================================== Checkpoint inhibitors that enhance the immune system against PD-1 and
PD-L1 show great promise, having substantially improved the prognosis
for patients with several advanced cancers, including melanoma, renal
cell carcinoma, non- small cell lung cancer, Hodgkin lymphoma, and head
and neck cancer.

As promising as they are, these therapies are also associated with
a unique set of side effects, called immune-related adverse events
(irAEs), believed to be the result of an immune system overstimulated
by the therapy. While these side effects are generally treatable, they
can in rare cases be very serious, even fatal. In addition, there's
currently no way to predict which patients will develop irAEs before
starting treatment, requiring clinicians to watch and wait after treatment begins. Notably, the toxicity from checkpoint therapy does not appear to
be associated with a patient's cancer or their response to the treatment, supporting the idea that it is a patient-specific reaction.

With a growing need to identify which patients are at risk for irAEs, investigators led by Joanne B. Weidhaas, MD, PhD, MSM, of UCLA Jonsson Comprehensive Cancer Center, vice chair Department of Radiation Oncology,
and director Division of Molecular and Cellular Oncology at UCLA Health, examined DNA signatures in 99 patients, looking for patterns that would indicate if inherited DNA biomarkers would predict toxicity. In findings published in Journal for Immunotherapy of Cancer, they report that they
were able to identify a biomarker panel that predicts toxicity with 80% accuracy.

"These findings represent an important step toward personalizing
checkpoint therapy, the use of which is growing rapidly," said
Dr. Weidhaas. "While we are still at the early stages of understanding
the mechanisms by which these germline mutations regulate immunity and the systemic stress response, our repeated findings that these variant panels
can predict systemic toxic responses to cancer therapy are potentially paradigm-shifting." The authors of the study say applying these findings
may improve clinicians' ability to offer truly personalized cancer
therapy by enabling consideration of toxicity along with other data that
can predict patients' response to treatment. "As the efficacy of cancer
therapy improves, resulting in higher and higher rates of long-term cancer control," they write, "cure without harm will only become an increasingly important endpoint." Funding: JW was supported by NCI Grant CA238998.

Competing interests: JW has created intellectual property that was
patented at Yale University and licensed to MiraDx, a company that
she cofounded. MiraDx has developed miRSNP panels that were applied to
blinded samples in this analysis.

========================================================================== Story Source: Materials provided by University_of_California_-_Los_Angeles_Health_Sciences.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Joanne Weidhaas, Nicholas Marco, Aaron W Scheffler, Anusha Kalbasi,
Kirk
Wilenius, Emily Rietdorf, Jaya Gill, Mara Heilig, Caroline Desler,
Robert K Chin, Tania Kaprealian, Susan McCloskey, Ann Raldow, Naga
P Raja, Santosh Kesari, Jose Carrillo, Alexandra Drakaki, Mark
Scholz, Donatello Telesca. Germline biomarkers predict toxicity
to anti-PD1/PDL1 checkpoint therapy. Journal for ImmunoTherapy of
Cancer, 2022; 10 (2): e003625 DOI: 10.1136/jitc-2021-003625 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220203083604.htm

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