Potential to enhance efficacy of checkpoint blockade

A patient was on Yervoy for many months but progressed. A painful spinal lung met developed. The clinicians (Dr. James Allison's colleagues at Memorial Sloan in New York) decided to irradiate for pain relief. Amazingly, one month later, when Yervoy was resumed, all other progressing tumors regressed (not just the sole irradiated tumor). They documented this exciting finding in a case report.

Later, some oncologists at Stanford Cancer Center read that case report. The Stanford physicians decided to try the same strategy on one of their patients. They believe they were able to reproduce the effect and documented it in the following journal response.

As a result of this extremely exciting observation, there is now a trial of combination radiation + Yervoy for metastatic Stage IV Melanoma right up our backyard at Stanford Cancer Center . The thought is that the radiation or cryoablation damages the tumor, releasing antigen, thus priming the immune system (like a vaccination effect). However, by itself, this is usually insufficient to obtain an anti-metastatic abscopal effect. Now, with checkpoint blockade removing the brakes off the immune checkpoints, it is theorized that this may be a reliable way to obtain the abscopal effect. Hence the clinical trials.

The important implication for sarcoma patients and those with other cancers is that this strategy may very well apply to your cancer. Just because the trial is being done on metastatic melanoma does not imply the strategy may only work for melanoma. The reason for the Melanoma restriction, has to be because Yervoy was approved for Melanoma in 2011. This means the trial investigators can rely on insurance to cover the $100K cost per 4 infusions of Yervoy! 

The problem for rare cancers (like sarcoma) is it will be years before such a trial comes about. However, radiation and cryoablation are readily available a-la carte from any respectable cancer center. 

Combination cryo or radiation with anti-CTLA4 is available to you today—but you may need to sell the house... 

Yervoy is readily obtained off label. Cryoablation and radiation are established and should be easy enough to find an interventional radiologist to go along. Theoretically, one does not need full tumor kill with radiation or cryo. Just enough to release some antigen (theoretically). Personally, my strong preference is for cryoablation. The abscopal effect has been witnessed for decades with cryoablation alone (but effect is usually short lived). This implies greater immunogenicity as compared to radiation—somehow when cryoablation is done, the immune system is able to recognize live tumor cells as bad and go after them. It is theorized that this is because the dead frozen antigens remain in the body in-situ.

Also, radiation can have some serious side effects on the lung. Furthermore, if too much radiation is given to sensitive areas, there is the potential for long-lasting immunosuppression—which is counterproductive.

Unfortunately, as I have explained in this other post, unless you have melanoma, Yervoy (anti-CTLA4) can only be prescribed off-label for other cancers and will cost around $100K for 4 infusions. So, while this conceptual approach is available to any cancer patient, you may have to sell the house to make it a reality . . .