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Superresolution image of T-cells (green and red) surrounding a cancer cell (blue, center). Photo: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths/National Institutes of Health

A team of scientists say a biomarker test in development has shown a higher success rate than currently available tests at determining which patients with metastatic melanoma will respond to a certain type of immunotherapy, according to a new study published in Nature Medicine Monday.

Why it matters: Checkpoint inhibitors, which help the body's immune T-cells recognize and destroy tumors, have shown a range of success in treatments but also often come with serious side effects. Being able to predict if an individual's targeted cancer would respond to the immunotherapy is key to helping patients select their best treatment.

"Immunotherapy has made considerable strides in the past few years, with the advent of both checkpoint and cell-based therapies (e.g., cancer vaccines and CAR-T therapies).  These are truly exciting and encouraging, but there is a continuing mission and challenge to increase the efficacy of the treatments, extend them to more cancer types, and further increase their efficacy and the number of patients that can benefit from them."
— Eytan Ruppin, study author, University of Maryland

Background: Checkpoint inhibitors have been approved for treating metastatic melanoma but have had varied success. Their side effects can be life threatening, including inflammation of the lung, heart or neurologic problems.

What they did: The researchers used clinical data from 9 prior studies, plus they tested another 41 new patients (31 patients treated with anti-PD-1 and 10 with anti-CTLA-4, which are the two main types of checkpoint inhibitors for melanoma). This allowed them to evaluate a total of 297 samples.

  • In creating the biomarker (a characteristic that indicates the responses to a therapeutic intervention) they decided to target a gene signature found in a type of cancer found mostly in young children. Such tumors, known as neuroblastomas, often show spontaneous regression, disappearing partially or fully.
  • They took the gene expression featured in regression and created what they called an IMmuno-PREdictive Score (IMPRES) for each patient sample and ran it against the 297 samples.

What they found: IMPRES had a 83% accuracy rate, "outperforming existing predictors [which Ruppin says is just over 60%] and capturing almost all true responders while misclassifying less than half of the non-responders," the study states.

What they're saying: Mario Sznol, co-director of the cancer immunology program at Yale Cancer Center who was not part of this study, says the new research doesn't really address how IMPRES would work with patients who receive a combination of therapies, which is increasingly common. Plus, he adds:

"Although it appears to perform better than other predictive tests, there is still a small number of false negatives (depending on the threshold selected), which means that if you use this test, a small number of patients  who might benefit from treatment would still be excluded from treatment."
"Regardless, the new analysis could be a very useful tool in drug development, to divide groups much more accurately into very high versus very low response rates to anti-PD-1 alone, so combinations could be tested with much more precise historical response rates."

What's next: Ruppin says more research is needed "to test the utility of these scores in a controlled clinical trial that should be designed accordingly, prospectively."

Sznol says the field still needs a "comprehensive analysis" that would involve multiple biomarkers "to produce the most accurate discriminator of response and non-response."

Go deeper

Collins helps contractor before pro-Susan PAC gets donation

Sen. Susan Collins during her reelection campaign. Photo: Scott Eisen/Getty Images

A PAC backing Sen. Susan Collins in her high-stakes reelection campaign received $150,000 from an entity linked to the wife of a defense contractor whose firm Collins helped land a federal contract, new public records show.

Why it matters: The executive, Martin Kao of Honolulu, leaned heavily on his political connections to boost his business, federal prosecutors say in an ongoing criminal case against him. The donation linked to Kao was veiled until last week.

How cutting GOP corporate cash could backfire

Illustration: Aïda Amer/Axios

Companies pulling back on political donations, particularly to members of Congress who voted against certifying President Biden's election win, could inadvertently push Republicans to embrace their party's rightward fringe.

Why it matters: Scores of corporate PACs have paused, scaled back or entirely abandoned their political giving programs. While designed to distance those companies from events that coincided with this month's deadly siege on the U.S. Capitol, research suggests the moves could actually empower the far-right.

9 hours ago - Politics & Policy

Scoop: Kaine, Collins pitch Senate colleagues on censuring Trump

Sen. Tim Kaine speaks with Sen. Susan Collins. Photo: Andrew Harnik/AP via Getty Images

Sens. Tim Kaine and Susan Collins are privately pitching their colleagues on a bipartisan resolution censuring former President Trump, three sources familiar with the discussions tell Axios.

Why it matters: Senators are looking for a way to condemn Trump on the record as it becomes increasingly unlikely Democrats will obtain the 17 Republican votes needed to gain a conviction in his second impeachment.