By Paul Bildstein – Patient
I was diagnosed in 2009 at age 60 with CLL (Trisomy 12, unmutated) after a routine blood test. Initially on watch and wait, I was treated with FCR in 2012. The remission only lasted a year and by then I was also 17p deleted. Ibrutinib kept the disease under control until it became ineffective, then I went on to venetoclax. I obtained a consultation with Dr. Matthew Davids through the CLL Society’s Expert Access program who said that given my condition, the response to venetoclax was unlikely to be durable and I should be looking at other treatments, including CAR-T, if a trial was available. He also said that starting treatment sooner would be better than later because it is best to start while still relatively healthy. About this time, I was also following Dr. Brian Koffman’s experience with CAR-T therapy and was encouraged by his success. As anticipated, venetoclax began to fail and my options seemed to be, find a clinical trial now, or try a PI3K inhibitor which may get me through another year with potential side effects. I could be in the same position when it, too, failed and then a trial may not be available.
A CAR-T trial was available where I live, so I would not have to spend a month or more in another city during treatment which made the decision less daunting. The trial was part of a multi-center study (TRANSCEND CLL 004) for JCAR017 (liso-cel) which, from my research, appeared to be having good results and was a successor to Dr. Koffman’s treatment. Although the trial was recruiting and my disease was progressing, at first, I wasn’t “sick enough” to be enrolled because they wanted measurable disease to gauge the results. I went from the last ten years of seeing doctors and hoping that the disease hadn’t progressed to now hoping that it would, to become eligible for the trial while it was still recruiting. Finally, my platelets got low enough to qualify, and I was enrolled.
There were EKG and echo cardiograms to determine my general health and lots of bloodwork, a CT/PET scan, and bone marrow biopsy. I was in the ibrutinib arm of the trial and was given that in preparation for the CAR-T. Leukapheresis was done to collect the T cells in the beginning of July 2019 and the CAR-T cells were available at the end of the month. Chemotherapy (fludarabine and Cytoxan) was given Wednesday, Thursday, and Friday to make room for the new cells, with the weekend to rest. The CAR-T cells were given in two small injections on Monday, and I went home. There were doctor visits and bloodwork for the next three days to check progress. Part of the requirement for doing the trial as an outpatient was that I had to be within 60 minutes of the hospital. On Saturday night, I developed a fever greater than 100.4° and was admitted to the hospital where I spent the next several days feverish and physically miserable. I did not have the expected blood pressure drop, so the doctors spent a lot of time looking for an infection to explain the fever. It was finally concluded that the fever was due to the cytokine release and the doctor said I could have tocilizumab to relieve the symptoms, but he preferred I just let the fever run its course. By then the worst was over so I declined, and by Wednesday evening I was feeling better. I did not have the neurological problems that some people experience except for hand tremors that took about a month to subside. A bone marrow biopsy eleven days after the CAR-T infusion showed no evidence of CLL. I was discharged after six days in the hospital and was able to recuperate at home, although I had to be watched 24/7 for adverse reactions. It took about a month to get back to normal and now I feel fine, except that I get tired more easily than I think I should. At my 15-month checkup, there was still no CLL. I continue to have few B cells, so I need to be careful about infections and I receive monthly IVIG infusions to maintain my immune system. My doctor calls me a “success story” and says the results are “exciting” and, indeed, they are. When I ask about the prognosis, they say “We don’t know. This is so new there’s no data. When people in the future ask, we’ll tell them about you!” I hope to set a good example.
As for the cost, since this was a clinical trial, the sponsor picked up the expense for the treatment and testing. I was responsible for the doctor visits and hospitalization. I have a Medicare Advantage plan and the out of pocket costs were small compared to the ongoing cost of the CLL medications I had been taking. The physical cost was to undergo five bone marrow biopsies and eight PET/CT scans (so far), but that’s the price of admission for a clinical trial.
In talking with the trial coordinators, everyone’s experience with CAR-T is different. Success is not guaranteed, but in all, I believe CAR-T was the right decision for me.
Paul Bildstein is a retired mechanical engineer living in Pittsburgh. He was diagnosed with CLL in 2009.
Originally published in The CLL Society Tribune Q3 2021.