My CLL Hangs on by a Thread: Stopping Epcoritamab

As I said before, August 2025 marks two full years that I’ve enjoyed the benefits from my trial of epcoritamab, a bispecific T -cell engaging monoclonal antibody for my CLL. But the last remains of my chronic lymphocytic leukemia (CLL) have remained stubbornly persistent for about a year and half. I have been in a complete remission (CR) with normal blood counts, normal physical exam, and all my lymph nodes shrunken back to normal size when imaged since February of 2024. That was only six months after starting the trial for my high risk (del 17p, TP53 mutated, del 11q, complex karyotype, unmutated IGVH, NOTCH1, and more) relapsed CLL. This rapid response was reinforced when my testing for measurable residual disease (MRD) by next generation sequencing (NGS), specifically clonoSEQ testing showed only one or less clonal CLL cells per million in my peripheral blood and about 45 cells per million in the bone marrow. It seemed I was destined for a uMRD^-6 remission.

But the rapid fall in tumor burden has not continued. A year and half later, my CLL MRD testing in my blood stream remains the same. So have my routine blood counts and scans. I am still in a complete remission with detected measurable residual disease by clonoSEQ at the level of less than one per million cells (dMRD^-6). What’s new now is that the results are still unchanged through the end of July 2025. Four sequences were measured: 

·      one stayed the same at undetectable,

·      one stayed the same at less than one,

·      two moved from one per million to less than one per million. 

So essentially stable.  As far as know, I am the only one in the trial who has achieved a CR without also reaching uMRD^-6.  So close, but not there

I am not sure what benefit continuing to flog my T-cells with the bispecific antibody to kill my cancer cells will do. 

I am also not sure what harm it might be doing. 

I do know that my good B lymphocytes are missing in action as they are directly targeted by epcoritamab. I know my T lymphocyte subsets are low and that the ones that I do have are likely exhausted (and therefore ineffective) by two years of being called into action to kill all my B- cells, cancerous or not.

Not surprisingly with no B-cells and iffy T-cell counts and activity, early data shows infections are the leading cause of death in my trial.

I also know that once I go off the trial, it may be hard to restart epcoritamab “off label” as no bispecific is yet approved in CLL should I need it again. 

Psychologically, epcoritamab has been my security blanket. I feel I am doing something by staying in the trial, but am I really? It was hard for me to stop my ibrutinib, but when I did, I did fine for years. 

My past experience with relapses helps predict the future. Once my CLL reached one per million cells in the blood after my CAR-T, I was staring at a new treatment choice in less than two years. That treatment was epcoritamab. Will it take off faster this time? The timing of when I need treatment must be near prefect, as I almost certainly will be looking to a clinical trial for knocking back my recurring clone. Will there be a degrader or a new BCl2 inhibitor or dual inhibitor or combo trial that I could use when I need it? 

Still most bispecifics, when used for other lymphomas, are taking for a fixed duration such as two years, not forever. 

I thought last month would have been when I stopped. But I stopped the cordyceps instead on Dr. Danilov’s advice with a plan to recheck my T-cells. Regardless, I will be surprised if I continue epcoritamab any longer. 

Despite a rough take off with cytokine release syndrome (CRS) and adverse events over the first rocky two months, it has bought me two great years of a deep remission, and a chance for a long glide off therapy. I am very grateful for the trial and to the team that has cared for me led by Dr. Danilov, trial nurse Alex and GenMab for their flexibility and diligence in making this possible. I hope, but am uncertain, that others with CLL will be able to enjoy similar benefits.