Why Epcoritamab for My CLL Clinical Trial?

In my earlier post, I discussed why I elected to start my clinical trial early rather than waiting for my counts to fall or my symptoms to worsen.

I will again make the point briefly that it isn’t a question of if I would need treatment but only how long I could postpone it. My lymphocytes, while still low, are doubling fast, my nodes are getting bigger and are already significantly enlarged on my imagining, and my hemoglobin and platelets, though still normal, are trending down. It’s not if; it’s when.

So why did I choose this epcoritamab trial to knock back my CLL?

Some background of the drug.

Epcoritamab is a new monoclonal bispecific T cell engaging antibody, a BITE. It is approved in “relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy.” It is experimental in CLL.

It is a form of cutting-edge immunotherapy.

Antibodies are an important weapon in our immune arsenal. Monoclonal antibodies are man-made therapies for cancer, infections, inflammation, and more that have revolutionized the care of several medical conditions. They are all Y-shaped. With a bispecific antibody such as epcoritamab, the two upper arms of the Y are directed at two different targets. One arm attaches to CD20, labeling as the enemy all my chronic lymphocytic leukemia cells and all my healthy antibody-producing normal B-lymphocytes; both express CD20. This is exactly how rituximab and obinutuzumab (Gazyva) work.

But wait, there’s more.

Unlike rituximab and obinutuzumab, where both arms of the antibody are identical and attach to CD20, the other arm of epcoritamab attaches to CD3, which is found on all my T-cells. This means the T-cells are pulled very close to their cancer target, and the killing can proceed quickly without waiting for a random T -cell to float by and notice the targeted CLL or B-cell. Think CAR-T in a bottle.

It’s an immune therapy because we harness our immune system to kill the cancer. No toxic chemotherapy. Not even an enzyme blocker like Bruton’s Tyrosine Kinase (BTK) inhibitors like ibrutinib and others.

I like that.

Resistance can only develop if the cancer stops expressing the target marker, in this case, CD20. Then there would be nothing for the antibody to attach to on the CLL cells. This is how many other blood cancers escape other monoclonal antibodies and CAR-T therapy. This can and does happen in CLL, but it’s rare.

Another way the treatment can fail is because chronic lymphocytic leukemia patients often have wimpy T-cells that can show an “exhausted” profile. CLL might be a cancer of the B-cells that make antibodies, but it can have a malevolent influence on all parts of the immune system. T-cells, the immune soldiers, often become lousy at their job of being a serial killers in CLL patients. The more active the CLL, the weaker the activity of the T -cells. BTK inhibitors can improve T-cell activity and would be a smart addition to this trial, but that was not an option at this time.

Finally, another significant issue with antibody therapies is the concept of drug-to-target ratio. The more drug to target, the better. Kick it while it’s down; shock and awe.

My logic is that if I was going to use an immune therapy, it was wise to use it very early when my immune system was less corrupted, and the odds were more in my favor. The lower disease burden also reduces the dangers from cytokine release syndrome, where toxic chemicals are released due to the cancer being disseminated, and tumor lysis syndrome, where too much cancer is killed too fast for the body to handle.

I had an extraordinarily durable and robust response to my other immune therapy, CAR-T, giving me another reason to believe that this trial might be a repeat of that success.

Convenience was a factor too. I wanted this trial simply because it was easy to access, available and local. Moreover, I will know quickly if it works or not, and my other options will still be available if and when I need them. The proper sequencing of trials is not a trivial decision. 

There is no guarantee I will have another chance to try such an immune therapy. It wasn’t now or never, but maybe it was now, or who knows?

Another practical advantage is that if it does work, and I am most optimistic it will, the trial will supply my expensive medication for the next five years.

So, there are all the reasons why I jumped into this early trial. My thinking is unique to my circumstances. Your situation will be different. We are all different.

Stay strong; we are all in this together.

Brian