PD-1 checkpoint inhibitors

The recent discussion of immunotherapy under “Going Commando” has rekindled my experience of Pembrolizumab, a PD-1 checkpoint inhibitor.

Our immune systems have T cells that help fight off diseases. Cancer cells that express PD-L1 escape this by binding to PD-1 receptors on the T cells. By doing this they are able to hide from the immune system, using the same mechanism the body uses to create immune privileged zones around critical organs.

PD-1 checkpoint inhibitors are offered to patients who have tumours that meet a threshold percentage of at least 10% of PD-L1 cells within the tested sample (plus other criteria). In my case, TNBC, they are available in the metastatic setting or for advanced presentation of early stage primary cancer. I had it in the metastatic setting, with spread to my liver.  The immunotherapy removes PD-1, thus allowing the immune system to ‘see’ and work on the cancer. Of course it also removes the immune privileged zones around critical organs too. As such, it can be both a game changer in cancer treatment, and also life threatening. 

I started Pembrolizumab in May 23. It was a relatively recent authorisation for TNBC, so my breast oncology consultant was new to it. I was one of 2 patients starting on it. I was sufficiently worried about the adverse effects to arrange to speak to an oncologist working in melanoma, where it has been in use for much longer. Her own experience was consistent with the patient leaflets, with skin rash being a frequent issue, there being some cases of colitis, but most other adverse events being very rare.  The user reviews on the American drugs.com site showed the usual bias towards people who had suffered adverse effects with a typical review being “it killed my dad but the cancer had also been killed”. 

The first 3 infusions were trouble fee. Infusion 4 led to a rash, easily treated with topical steroid, emollient and antihistamine. Infusion 5 was crunch point. The first inkling I had was a raging thirst on the day I had my bloods done for the chemotherapy I was due to have the next day. (For TNBC they kickstart it with Paclitaxel or NAB-Paclitaxel alongside). By the evening I had been admitted to hospital with acute kidney nephritis. Thyroid function had also failed. Started on high dose steroids, which I am still using via a slow weaning programme, more issues emerged as the steroid dose reduced. Pneumonitis. Low level colitis. Inflammation in my spine affecting nerves in my left side limbs. Some 6 months on I am still managing these consequences. On the other hand a scan just after my last treatment showed my larger tumour had shrunk to a seventh of its volume and the smaller one to a third. A scan 3 months after that showed them still dormant and unchanged in size. I have subsequently had the residue ablated. I am realistic to know this isn’t the end of it but I appear to have survived both the upside and downside of the treatment, albeit with ongoing health consequences. I have no regrets but would be wary of recommending the treatment to others.