Keytruda immunotherapy for cancer is better than chemo in the treatment of Merkel cell cancer. So says a recent clinical trial of this immune treatment at Johns Hopkins Medicine, Baltimore. It showed that more than half of the patients with this rare, but potentially deadly, skin disease had long-lasting responses to this new type of treatment.
A Merkel cell cancer usually appears as a single painless lump on sun-exposed skin. In the Keytruda trial, a quarter of such patients had a complete disappearance of their tumors. And 70 percent were still alive two years after starting Keytruda (which is also known as pembrolizumab).
More Effective Than Chemo
Although this was not a randomized trial, the overall survival rate with immune therapy for cancer was very favorable “compared with historical data from patients treated with first line chemotherapy,” the Baltimore scientists wrote.
According to senior author Suzanne Topalian, MD:
Keytruda immunotherapy for cancer is “more effective than…traditional therapies, like chemotherapy. [It] provides an effective treatment for patients with this rare cancer. [It also] does not directly target cancer cells but rather removes constraints on the immune system’s natural ability to find and destroy cancer cells.”
The Johns Hopkins Medicine study involved patients at 13 cancer centers across the U.S.. An earlier report had appeared in the New England Journal of Medicine in 2016. For the current study the authors added 24 more patients.
Merkel cell carcinoma is officially an “orphan disease.” That means that doctors diagnose this rare cancer in fewer than 2,000 people per year in the U.S. Older people, especially those who have suppressed immune systems, are typical. The Merkel cell polyomavirus causes about 80% of these tumors. And ultraviolet light exposure causes most of the rest.
Keytruda immunotherapy worked against both virus-positive and virus-negative Merkel cells. It yielded high response rates and long-lasting progression-free survival (PFS) in both types.
Key Findings About Keytruda Immunotherapy
- 64% of Merkel cell patients tested positive for the polyomavirus.
- The objective response rate to Keytruda was 56%
- The complete response rate was 24%.
- The partial response rate was 32%.
- The 24-month progression-free survival rate rate was 48.3%,.
- The median PFS time was 16.8 months.
- The 24-month overall response rate was 68.7%.
- Grade 3 or greater treatment-related adverse events in 28% of the patients.
- Treatment discontinuation in 14% of patients.
- There was one treatment-related death.
Is PD-L1 So Important?
Cancer cells frequently produce a substance called PD-L1 as a way of blocking the immune system. PD-L1 helps shut off the body’s effective response to a tumor. So, not surprisingly, patients whose tumors expressed a lot of PD-L1 had a more vigorous response to treatment.
However, the authors found that patients whose tumors did not express PDL1 also responded to Keytruda immunotherapy for cancer. This is a very important finding. You see, it contradicts a widely held belief that tumors that do not express PD-L1 will not respond to Keytruda immunotherapy for cancer. (Breast cancer patients take note!)
Obviously there is more to the action of Keytruda and similar drugs than just blocking PD-L1. And this is what Tibor Bakacs, MD, PhD, of DSc, of the Hungarian Academy of Sciences, Shimon Slavin, MD, of Tel Aviv, and I suggested over five years ago in an article in Pharmacological Research.
Because of studies like this Johns Hopkins trial, many scientists no longer consider PD-L1 a necessary precondition for giving patients immunotherapy for cancer.
In fact, the tide seems to be turning against assigning a key role to PD-L1. Last month, two influential doctors, David P. Ryan, MD, of Harvard Medical School, and Christopher G. Willett, MD, of Duke University Medical School, wrote at UpToDate.com (in reference to a different kind of cancer):
“In our view, PD-L1 over-expression should not be used to select patients for treatments targeting the PD-1 pathway.”
This represents a big change in how doctors choose candidates for Keytruda immunotherapy for cancer or other immune checkpoint inhibitors.
Along these lines, several months ago, I published a blog on how to predict if immune checkpoint inhibitors like Keytruda will work for any particular patient. You will notice that PD-L1 status was not on that list.
Finally, Merkel cell tumors can be caused by a particular virus. But some other more common cancers are also caused by viruses:
- EBV = Epstein-Barr virus can cause of B and T cell lymphomas, Hodgkin’s disease, leiomyosarcomas, and nasopharyngeal carcinomas
- HHV-8 = human herpes virus is a cause of Kaposi’s sarcoma
- HPV = human papillomavirus can cause of cervical cancer
- HTLV-1 = human T lymphotropic virus type 1 is a cause of adult T cell leukemias.
So, how does this relate to the latest findings with Keytruda immunotherapy for cancer? Well, according to William Sharfman, MD, an oncologist at Johns Hopkins Medicine:
“These findings could be a precursor to developing more effective treatments for other virus-related cancers, which account for about 20 percent of cancers worldwide.”
Therefore, people who are dealing with the above cancers should pay special attention to these results with Keytruda immunotherapy for Merkel cell cancer. This includes cervical, head and neck, leukemias and lymphomas.
Non-Virus Merkel Cell
But non-virus-related Merkel Cell Cancer also had a high number of genetic mutations. Sounds bad, right? But fortunately for us, a high rate of mutations (also called the “total mutational burden”) predicts a high rate of response to immunotherapy for cancer.
Toxicity of Keytruda
Overall, most patients tolerated this Keytruda immunotherapy for cancer well. However, in the study 28 percent did experience serious (grade 3 to 5) side effects.
Keytruda was even responsible for the death of one patient.
Thus, Keytruda immunotherapy for cancer is a two-edged sword. Yes, it unleashes powerful immune forces. But it can also backfire against the patient and even (rarely) result in a tragedy.
In fact, as early as 2012, my colleagues Dr. Tibor Bakacs, Jitendra N. Mehrishi, PhD, of Cambridge University, UK, and I suggested as much in an article in the journal Immunobiology. We recognized that use of the first such immune checkpoint drug, Yervoy, represented “an important therapeutic strategy against cancer.” But, at the same time, we warned of the possibility of widespread autoimmune toxicity in the patients.
At the time, many people thought we were being alarmists. But now it is universally known that many patients get sick, and some even die, from the various effects unleashed by this treatment.
This certainly does not mean we should abandon Keytruda immunotherapy for cancer or the use of other checkpoint drugs. Instead, doctors can make the toxicity of drugs like Keytruda manageable by giving combinations of drugs in much smaller amounts. Then, these small doses need to be merged into a comprehensive “holistic” treatment, which includes intense immune stimulation.
And, in fact, this is exactly how Ralf Kleef, MD of the Kleef Clinic in Vienna Austria, has achieved some remarkable remissions in advanced cancer.