William Wierda, MD, PhD: CLL14 demonstrated improvement in progression-free survival, no difference in overall survival of venetoclax, obinutuzumab versus chlorambucil, obinutuzumab; both oral agents were given for a year. And it was in a population with a high SEER [Surveillance, Epidemiology, and End Results] score, which tended to be an older population. So one question I have, and that people ask commonly is, are we willing to extrapolate that data into the younger, fitter patients? Is venetoclax, obinutuzumab a regimen that we consider for those patients? I wonder if you could give us your thoughts on that.

Shuo Ma, MD, PhD: Right. Even though the CLL14 has been on the relatively older patient population with comorbidities, I think the efficacy from the venetoclax plus obinutuzumab combination is definitely quite striking and comparable to what we’re seeing with the BTK [Bruton tyrosine kinase] inhibitors. And time-limited therapies are especially appealing for younger patients, those who would like to get started on the treatment but not to be on indefinite treatments, like a BTK inhibitor. So we’re happy. I think clinically we’re happy, definitely, extrapolating that potential benefit in younger patients. And we have seen, at least in the relapsed setting, we have done trials with venetoclax showing benefit in patients in all age groups, so I don’t think the age group would make a huge impact on the clinical benefit.

And so, another thing to consider when we’re choosing a BTK inhibitor versus venetoclax-based therapy is whether a patient is willing to devote the time to have a very time-intensive upfront therapy. When I’m discussing with my patients, I will say, “Choosing the venetoclax plus obinutuzumab combination, you almost have to devote a weekly commitment to come in for almost 2 months. You have to devote a certain amount of time in the clinic, and if you have good renal function, we can manage as an outpatient, if your disease burden is not high risk. If you have high risk for TLS [tumor lysis syndrome] or you have impaired renal function with relatively high disease burden, then we have to potentially admit you, at least for the first 2 weeks of dose ramp-up for venetoclax.”

I think it depends, when choosing treatment for the patient, it’s also up to the patient’s preference whether they’re willing to devote their upfront time to buy the time-limited therapy, versus with BTK inhibitors, it’s relatively easy, and doesn’t really require too much of the time monitoring from the patient. So, I think each treatment has its own appeal.

Stephen Opat, MBBS: Can I add, the venetoclax, obinutuzumab combination is going to be examined in the CRISTALLO study, which is comparing that combination with FCR [fludarabine, cyclophosphamide, rituximab] in fit patients or BR [bendamustine, rituximab] in patients who might not be suitable for FCR [fludarabine, cyclophosphamide, rituximab]. I think that study is about open or might have just opened, so it will take a few years before that reads out.

Carolyn Owen, MD: And then there’s the CLL13 study by the German group, which will also be looking at venetoclax versus chemoimmunotherapy. The only thing I say in reference to, I recognize for the patients there’s a lot more work, it’s very onerous, the initiation of a therapy on the venetoclax and obinutuzumab, particularly. It’s not an option that we have currently in Canada, but even just venetoclax on its own. But we need to remember, and this what I tell the patients, is that ideally every patient is going to receive both agents at some point. And it’s unlikely that the difficulty of coming into the clinic multiple times, the awkwardness of the intensity of the monitoring, is going to get any better with a subsequent line of therapy. The patient’s not going to get younger, fitter, or likely live any closer to the institution. So I usually remind them, “You are going to have to do this at some point. It’s a matter of deferring it to the next line of therapy, or just digging your heels in and starting now with the difficult one.” And a lot of patients actually hadn’t, nobody likes to think about the future, but ideally every patient will get both of the agents at some point.

Transcript Edited for Clarity