BTK Inhibitors Could Replace Chemotherapy in Mantle Cell Lymphoma Treatment

While chemotherapy is widely used in the frontline treatment of mantle cell lymphoma (MCL), earlier use of BTK inhibitors such as Imbruvica (ibrutinib) may soon make chemotherapy obsolete for some patients, according to new data presented at the 2019 American Society of Hematology (ASH) Annual Meeting.

Simon Rule, a professor of hematology at Plymouth University in the United Kingdom and ASH presenter, sat down with OncLive®, CURE®’s sister publication, at the meeting to discuss his recent findings, including research that could change the way some patients with this rare and aggressive type of lymphoma are treated.

OncLive®: Could you give us some background on your recent work in the MCL field, and what you’re presenting on here at ASH?

Rule: What we did was just a further follow up on a group of patients that we’ve been looking at for a while now. It’s three trials of patients receiving single-agent ibrutinib, and basically, it’s just long-term follow up to see whether with longer exposure to a drug, you’re developing side effects or whether the efficacy is still there. It’s basically an additional safety analysis.

What we found was that a portion of patients still remain on the drug, with a seven-and-a-half-year follow up, and there’s no emergence of new toxicity, which is very encouraging. But perhaps the most important bit of the analysis was, for the first time, we looked at how response to ibrutinib compared with prior therapies.

With MCL, when you use chemotherapy, each time you use a different chemotherapy, you get less of a response. This is a common thing you see with lymphomas. But with MCL, when you use ibrutinib, what we find is that the ibrutinib response is generally better than the prior chemotherapy. In one group, it’s spectacularly better, and that’s the patients that get the most benefit from the chemotherapy.

So that’s the group where people would be more inclined to use chemotherapy again, but actually that group gets the most benefit (from ibrutinib). In fact, the average benefit is more than a year from the second therapy compared with the first. This is against what one normally finds with chemotherapy. So, it just further encourages use of these drugs earlier in the treatment paradigm.

What are the next steps with ibrutinib and other BTK inhibitors in MCL?

It’s clear that the earlier you use the drugs, the better the outcome. So, the next steps are using the drugs up front. We’ve just seen a presentation just now of using ibrutinib, rituximab (Rituxan) in asymptomatic patients with high response rates; you can question whether you need to treat those patients at all, but nonetheless there are high response rates.

I’ve got a trial running in the UK comparing ibrutinib/rituxumab versus chemotherapy in the frontline for elderly patients. That’s really going to tell us whether it’s better than chemotherapy.

We’ve also got data looking at ibrutinib plus venetoclax (Venclexta). We’ve just seen relapsed data, and there was a poster yesterday from myself and my French colleagues looking at ibrutinib and venetoclax plus obinutuzumab (Gazyva) in the frontline, and having very, very impressive results: in 15 patients, 14 of them had MRD (minimal residual disease)-negative, complete remissions.

I think it’s very clear that early use of the drug, probably in combination, is the way we’re going to go with this disease, and chemotherapy may well become a thing of the past.