CLL Treatment | How Standard of Care Therapy Has Evolved

Transcript:

Jeff Folloder:  Back when I started this CLL thing, FCR was referred to as the gold standard of care, and I know we’re not doing chemo so much anymore. I guess that the gold standard now is the combination of venetoclax (Venclexta) and ibrutinib (Imbruvica). Dr. Wierda, just how effective is that gold standard, and more importantly, what comes next when that gold standard fails? 

Dr. William Wierda:   Yep. So, maybe just back up a little bit. I would say that in terms of first treatments, we have two gold standards. One is maintenance treatment with a second-generation BTK inhibitor. That’s a continuous treatment. It’s extremely effective. We know from our work with ibrutinib that the average duration that that treatment will work, although patients have to stay on the treatment all the time, is about nine years, and it’s probably better with the second-generation drugs, acalabrutinib (Calquence), zanubrutinib (Brukinsa).

And so, that is a gold standard. It’s a maintenance. It comes with specific side effects and toxicities, and it requires the patient to stay on treatment continuously, but it’s extremely effective and would be considered one gold standard. The other gold standard is time-limited therapy. And particularly, venetoclax-based therapy, venetoclax plus obinutuzumab (Gazyva), which is an IV medicine.

The venetoclax is given in that combination – one year. The IV medicine, obinutuzumab, is given for the first six months. And we’ve done work with other combinations, as you indicated, that are venetoclax-based treatment. Ibrutinib plus venetoclax, acalabrutinib plus venetoclax, acalabrutinib plus venetoclax plus obinutuzumab. And then we’ve most recently done a trial with pirtobrutinib (Jaypirca), venetoclax, obinutuzumab.

Those combinations are very active, very effective. We’ve been able to put those combinations, venetoclax plus ibrutinib and venetoclax plus acalabrutinib, into the NCCN guidelines. So, one would consider them the gold standard because they are in the NCCN guidelines. However, they’re not FDA-approved. We can get access to them for our patients because they’re in the NCCN guidelines. But most of the clinical trials now and the new data that we’ll see relate to those combinations of targeted therapies.

And I expect that we will eventually have not just two gold standards or – that being BTK inhibitors and venetoclax combination with obinutuzumab – but multiple gold standards as first treatment. And those being venetoclax or a new drug that will likely get approval in the next few years, sonrotoclax, that works similar to venetoclax combined with a BTK inhibitor with or without a CD20 antibody. So, that tends to be the challenge. There’s more than one gold standard. There are different strategies that we can take with our patients, and optimizing and selecting therapy for individual patients is more the discussion these days with regard to getting the best outcome for our patients.