What’s new in immunotherapy for prostate cancer?

One of the earliest immunotherapies approved by the Food and Drug Administration (FDA) for the treatment of cancer was a vaccine called sipuleucel-T. It’s been used to treat metastatic prostate cancer since 2010.

Since then, the introduction of immune checkpoint inhibitors has revolutionized the field of cancer treatment. And patients with some types of cancer — such as melanoma and lung cancer — have benefitted greatly from that discovery. Others, including those with prostate cancer, have not benefited as much.

At MD Anderson, we are working hard to understand why, and what can we do to change it.

Few T cells in prostate tumors help thwart immune checkpoint inhibitors

A major reason immune checkpoint inhibitors don’t work as well against prostate cancer is that the gland doesn’t contain a lot of T cells, which do much of the immune system’s heavy lifting when it comes to killing cancer. 

Melanoma (a skin cancer) and lung cancers generally have more T cells. So, an immune checkpoint inhibitor, which takes the brakes off of T cells and allows them to keep working, is much less effective in a cancer that doesn’t have many T cells to begin with.

New class of immunotherapy makes the most of existing T cells

But a new class of immunotherapy, called T cell bi-specifics, also known as T cell redirectors, could be changing that. These drugs bind one part of themselves to a tumor cell and the other part to a T cell. Forcing the two cells together has yielded some remarkable results. 

A recent clinical trial involving an experimental drug called AMG 509/Xaluritamig, saw a reduction in blood levels of prostate-specific antigen (PSA), a tumor marker, in nearly half of participating patients. A quarter of participating patients whose tumors could be measured saw shrinkage on scans. This drug targets a protein called STEAP-1 on prostate tumor cells and an antigen called CD3 on T cells. Several clinical trials involving that drug are now underway at MD Anderson.

Another just-launched study, led by my colleague Sumit Subudhi, M.D., Ph.D. in collaboration with Brian Chapin, M.D., and me, is providing a unique lens to study these drugs. This clinical trial is using a first-in-its-class drug called REGN5678, which binds the prostate-specific membrane antigen (PSMA) on tumor cells and the CD28 protein on T cells. 

Patients with prostate cancer who will undergo surgery will receive the experimental drug for six weeks, then have their prostate glands removed. Analyzing the entire gland will help us understand exactly what the drug is doing, how it’s working and how we might be able to combine it with other drugs in the future, to potentially improve effectiveness.

Learning about new therapy’s side effects

We’re also looking at side effects. Immunotherapies can be very effective at attacking tumors. But they can also sometimes cause unwanted side effects, where the immune system starts attacking the body’s tissues and organs. 

As with CAR T cell therapy, the two major side effects of T cell bi-specifics are:

• Cytokine release syndrome (CRS): This causes flu-like symptoms such as high fever, fatigue and body aches in milder cases, and blood pressure problems and other issues in more severe cases. We treat CRS with steroids and a drug called tocilizumab.
• ICANS: This side effect, which stands for immune effector cell-associated neurotoxicity syndrome, makes patients confused or disoriented. They may also temporarily lose the ability to speak. Steroids are the most effective treatment.

As T-cell bi-specific drugs are new, we are also seeing new kinds of immune side effects.  But we are actively studying how to find a balance between keeping a good immune response to these drugs and separating it from the unwanted side effects. We monitor the patients receiving these treatments very closely.

Our hope for the future of prostate cancer treatment: the possibility of immune memory

Prostate cancer feeds on testosterone. So, we’ve known for more than 70 years that if we reduce or eliminate testosterone levels using hormone-suppressing drugs, prostate cancer will initially shrink. Unfortunately, prostate cancer often learns how to grow despite the absence of testosterone, making it what’s called “castration-resistant.” 

The average lifespan of a patient after a diagnosis of metastatic castration-resistant prostate cancer is two to three years. Approximately 30,000 men die of this disease annually.

So, the possibility of immune memory makes this form of therapy exciting. Immune memory is why vaccines work, and why once you’ve had chicken pox, you won’t get it again. Your immune system learns how to fight off certain threats it’s seen before and destroy them if it ever encounters them again.

If we can successfully harness this therapy’s power to create immune memory for our prostate cancer patients, then they might finally be able to achieve long-term benefits. So, this is a really exciting time to be studying immunotherapy.

Clinical trials for prostate cancer are usually only open to patients who have advanced-stage, metastatic disease. That’s where the need is greatest. But there are also studies for patients who have early-stage prostate cancer with a high risk of recurrence. Talk to your oncologist if you’re interested in enrolling to see if one might be a good option for you.

Bilal Siddiqui, M.D., is a medical oncologist who specializes in the treatment of prostate cancer and other genitourinary cancers.

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