Every now and then, someone writes a comment, and my response to it goes on so long that it ends up being as long as some of my posts. In that case, I decide it's easier to just write a response as a post in the main blog, rather than in the comments.
This post is one of those responses.
Reader Shelly wrote a comment last week, asking if I'd heard about the combination of Ibrutinib, Obinutuzumab, and Venetoclax for treating Follicular Lymphoma. Someone in the FL Facebook group had written about his experience in a clinical trial with this combination. He said the trial oncologist estimated that the combination had knocked out his FL in about 3 weeks, confirmed by a PET scan three months later, though he continued in the trial for almost two years. He said he had stage 3 FL, with 10 high burden tumors.
It sounds like an excellent trial. I'm very happy that it was successful for that patient.
The combination of Ibrutinib, Obinutuzumab, and Venetoclax has already been pretty successful for Chronic Lymphocytic Leukemia (CLL), another slow-growing blood cancer. That doesn't mean it will work in all blood cancers, of course.
Obinutuzumab is a monoclonal antibody (like Rituxan) that has been approved for use on FL. Ibrutinib is a BTK inhibitor that has been very successful in treating several blood cancers, but it has never had a successful trial for treating FL. Venetoclax is similar, in that it has been successful in treating several blood cancers, but not FL.
If only one out of three has been successful in treating FL, is it worth trying them in combination?
Absolutely. Cancer is such a complex thing, it's hard to know what is going to work. Inhibiting or blocking one thing on its own might not work, but targeting and blocking several things at once might do the trick.
The Ibrutinib, Obinutuzumab, and Venetoclax combination for Follicular Lymphoma is in a phase 2 trial, which is probably the trial that the person from the Facebook group is a part of. I can only find one source discussing any results from the trial -- an article in the medical journal Blood from November 2022. In it, the authors discuss the early results of the trial. Eight patients were involved, with a 12 month follow-up. At that time, all 8 had shown a Complete Response, which is impressive. Side effects included fatigue, diarrhea, low white blood cell counts, rash, and low platelet counts. Two patients left the study by choice, and another had to leave because of side effects. The other 5 remained in the trial.
I'm not aware of any other published follow-up.
According to ClinicalTrials.gov, the trial is still ongoing, actively recruiting patients. The goal is to have a total of 40 patients in the trial, so if they are still recruiting, they probably haven't met that number yet, though the researchers estimated that they would finish recruiting in a few months.
It brings up an important question -- if a clinical trial had a 100% Complete Response Rate early on, why didn't it immediately get more patients?
I think one reason is purely practical. The trial is being conducted at four cancer centers in California. Many large trials are conducted in canters all over the country, and often in multiple countries. With lots of other options, I don't think many patients will travel to California. So the participants are likely limited to FL patients in that one state.
And another reason is one I just mentioned -- there are lots of other treatment options available. As I keep saying, CAR-T and bispecifics are what get lymphoma specialists excited these days. Treatment with a combination like this, especially if it requires travel, probably isn't something that oncologists will recommend.
And there could be a third reason, having to do with the combination itself. It's possible that some oncologists would say "One out of three isn't good enough," despite the early success of the trial.
All of that is just speculation from me -- I have no insights into why specific oncologists would or would not recommend a trial.
This seems like an excellent time to remind everyone that I am not a medical doctor, or even a cancer researcher. I'm just a Cancer Nerd -- a patient who reads a lot. The best person to talk to about treatment options is always your own oncologist.
So if the question is, would this trial be something to talk to my oncologist about?
The answer is, Absolutely, especially if you live in California. The published data from the trial is limited, and the lived experience of the person from the Facebook group is fantastic. But an oncologist would be the one to suggest whether or not it is worth looking into.
Shelly, I hope this answers your question. Thanks for the comment.
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