Tuesday, August 1, 2017

Cures

A cure for cancer is like an alchemist's dream of turning lead into gold: basically a category error. You can't cure cancer because cancer is not one thing. There are lots of cancers, and each one is different in exactly the way you might hope to cure it. There are themes in cancer treatment, though, and right now the hot one is immunotherapy. Even that term hides a lot of variation, because our immune systems are really quite varied in their triggers and modes of action, and trying to get them to respond to an attack from within, when they have demonstrably failed to do so in the first place, is hard.

So right now, here is an incomplete list of promising immunotherapy approaches to cancer: 1) monoclonal antibodies; 2) checkpoint inhibitors; 3) chimeric antigen receptor T cells (CAR-T); 4) vaccines. Since every cancer is different (even every cancer called by the same name, like multiple myeloma) they don't all work on every cancer or even everybody with the same "type" of cancer.

Myeloma and other cancers that originate in the bone marrow (mostly leukemias and lymphomas) seem to be a little more responsive to all of these approaches than "solid" tumors like colon cancer or breast cancer. But everybody's cancer is a snowflake and some of them will just do stuff that defies the conventional wisdom. Recently there have been news reports about immunotherapy successes with myeloma and other cancers (and some major failures as well). Here's a status report, from my own perspective.

Monoclonal antibodies. Right now, two of these have been approved by the FDA for myeloma, Darzalex (daratumumab) and Empliciti (elotuzumab). [Every drug has a generic name (lowercase) and a brand name (Uppercase)]. At the moment, Darzalex looks like the more promising of the two, with some good long-term results.

Checkpoint inhibitors. The idea here is to defeat the mechanism that many tumors use to evade attack by the immune system. The most famous of these drugs is probably Keytruda, which has been very successful in treating melanoma (see Jimmy Carter) and has been the first drug ever approved by the FDA for a specific pattern of genetic mutations regardless of the tissue in which the tumor originates. Sadly, for those of us with myeloma, Keytruda trials have been halted by the FDA because of  a recent spate of patient deaths.

CAR-T. These are the current cutting edge of "personalized" cancer treatments. T-cells harvested from a patient (by apheresis) are engineered in a lab so that they have receptors for the specific antigens expressed by the patient's own tumor cells, and are then infused back into the patient. This can have spectacular results, but sometimes causes really severe reactions including sudden death. In myeloma, two recent (small) studies have had great results. I'm thinking hard about this option.

Vaccines. The idea here is to train the immune system to something that triggers a response against the tumor, so it's kind of like CAR-T, except it's in vivo. Early days here, stay tuned.

I am (we'll call it) lucky enough to be responding to the treatment I'm getting now (Ninlaro-Revlimid-dexamethasone), so there is no obvious reason to do something rash at the moment. There is a CAR-T trial at Mayo that is currently recruiting patients, and I think I qualify, so we will discuss this with the docs when we visit at the end of August. There are a few other trials that might be worth looking at, too. Some of these have nothing to do with immunotherapy, and that's not necessarily a bad thing.

Drifting off the point a bit: John McCain has been a warrior in real life, but he shouldn't be judged on his "fight" with cancer on the basis of how long he survives now that he has been diagnosed. As I've said before, a cancer patient isn't a combatant--he or she is the battlefield. We survive or not (not; it's only time that varies) largely as a function of things that we have no role or agency in: our genetic underpinnings; the accumulation of random mutations in single cells; exposure to environmental toxins that we can't see/hear/feel/smell/taste and that are not currently known to do us harm; exposure to things that we do know can cause harm but we can't possibly avoid (like cosmic rays and radiation from the earth's surface).