Yesterday, the FDA granted accelerated approval for the combination of Zanubrutinib and Obinutuzumab for Relaped/Refractory Follicular Lymphoma patients who have had at least two previous treatments. this is good news -- we have another option.
Zanubrutinib is an inhibitor. It's different from the PI3K inhibitors that have been approved (and then pulled) in the last few years. But it works on the same very general principle of inhibiting (or stopping) a process from happening that cancer cells need to grow and live.
Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor. BTK is an enzyme that plays an important role in B cells developing. B cells are of course the cells that turn cancerous in Follicualr Lymphoma and a bunch of other blood cancers. So stopping their development is a way of holding off the cancer from growing.
Obinutuzumab is a monoclonal antibody, like Rituxan, but with some differences. It's the "O" in a treatment like B-O or O-CHOP, and probably the most successful attempt at an alternative to Rituxan.
The accelerated approval is based on the results of a phase 2 trial known as the ROSEWOOD trial. In this trial, patients were given the Zanubrutinib-Obinutuzumab combination and the results were compared to patients who were given just Obinutuzumab. The comparison involved looking at two statistics -- Overall Response Rate and Duration of Response.
The researchers found that 69% of the Z-O patients had a response (whether it was Complete or Partial), compared to just 46% of patients who had just O. As for Duration of Response (DOR), after a median 19 months, the median DOR was not yet reached for the Z-O combination. In other words, more than half of the patients in the trial were still getting a response after that time. For the O patients, the median DOR was just 14 months.
As for side effects, there were no surprises. Zanubrutinib had already been approved for other blood cancers, and the Z-O combination didn't result in any new or worse side effects than have already been reported. These include diarrhea (18.2% in the Z-O patients and 16.9% in the O patients), fatigue (15.4% and 14.1%), and fever (13.3% and 19.7%).
As I have said before, there are several BTK inhibitors already approved for other blood cancers, but this is the first for Follicular Lymphoma. It's interesting -- it would make sense that a BTK inhibitor would work on FL, but so far, none have been successful, including Ibrutinib, which was a game-changer for CLL patients. Not sure why. But this combination seems to be working for some patients.
And it needs to be noted that this comes form an accelerated approval. Obviously, OS was not even considered as a primary endpoint or way of measuring success. That's likely because this is an approval for R/R FL, and finding a treatment that keeps patients from needing further treatment is the priority. But as an accelerated approval, the combination will still need further clinical trial testing to get permanent approval. We'll keep an eye on that.
No one is really talking about it much online just yet, maybe because Zanubrutinib is already pretty well known, so there's less excitement. But it will be interesting to see how often this gets prescribed from here. If any of you have a conversation with your oncologist about this, please let me know. I'd love to hear what an expert thinks.
Stay well.
2 comments:
Hi Bob! I hope you're well and continued thanks for the work you do on your blog! So I just had four rounds of BO (Oct-Jan) for my refractory FL. It was successful and I had a full response. Something I haven't ever had with R only since I was diagnosed. More importantly, the fatigue that has plagued me since diagnosis is now gone. Truly feel like a different version of myself.
My doc and I discussed ZO as a possible treatment for my next line (which hopefully will be in 3-5 years or more out!). CAR-T will also be an option at that point to consider. I'm definitely interested in ZO because the side effect profile seems less frightening to me. We'll see where things are when I need another round of treatment.
Just as a side note, I tolerated Obinutuzumab much better than Rituxin. They still went at the slowest infusion rate but no reactions and was able to complete in one day. Not always the case for Rituxin that often took multiple days for me to complete.
Hello, Terrilyn! So nice to hear from you! I'm glad you're doing well, and very happy that you had success with the BO. It sounds like the O is ticket for you, so the ZO makes sense. I hope it's a long, happy time before you even need to think about it, but great that the option is there and you feel good about it. I hope you're still writing.
Take care.
Bob
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