New Possibilities and Advances in Mantle Cell Lymphoma Treatment: Part 5

In this expert roundtable series, Kami Maddocks, MD, The Ohio State University, Columbus, Ohio, leads a 5-part roundtable panel discussion on updates in mantle cell lymphoma with Jia Ruan, MD, PhD, Weill Cornell Medicine, New York, New York, and Krish Patel, MD, Swedish Cancer Institute, Seattle, Washington.

In the fifth video of the series, the members of the panel review new possibilities and the latest advances in the treatment of patients with mantle cell lymphoma. 

Transcript:

Kami Maddocks: Welcome to Oncology Learning Network. My name is Kami Maddocks from the Ohio State University James Comprehensive Cancer Center, and I will be moderating today's discussion on mantle cell lymphoma. I am joined today by a distinguished panel of experts in treating mantle cell lymphoma. 

Let's talk about some of the data in terms of new or ongoing clinical trials and future treatments. Maybe if both of you could touch on what you see as exciting, or what ongoing trials in the frontline or relapsed setting that you look to see results of.

Jia Ruan: Following up on the previous discussion, I think for the new study in the frontline setting, we talked about introducing some of the novel agents BTK inhibitor onto the chemoimmunotherapy backbone for younger patients [who are] physically fit. That is the TRIANGLE study, which is ibrutinib with induction and maintenance onto the backbone of R-CHOP or DHAP type of backbone. 

And then for patients who are more elderly, which is typical for the mantle cell lymphoma patient population, then the backbone that we predominantly use would be bendamustine-rituximab (BR). For that, ibrutinib addition was for the induction and maintenance and that's the SHINE study. I would be very eager to see if the similarly designed ECHO study, which is adding acalabrutinib, was similar. I think almost exact same design to BR induction and then maintenance, see if that would bring about either similar or different outcomes.

I think the dividing aspect could be just a balancing act of efficacy and also toxicity, whether some of the toxicity that we've seen with ibrutinib could be blunted by the acalabrutinib just because they're slightly different toxicity profile. Especially we like to think that acalabrutinib may be better tolerated in a more elderly population, which is typical, and that's what the ECHO study is targeting for. I think that that would be something that [would] help us to decide [about] adding a BTK inhibitor to a BR-based backbone. How much clinical benefit can we anticipate?

Krish Patel: Dr Ruan talked about the frontline setting, so maybe I'll take some of the trials that I think are exciting in the relapsed/refractory setting. We expect to see data from the SYMPATICO trial, I think at ASH. That's a combination of venetoclax with a covalent BTK inhibitor in this case, specifically ibrutinib. I think that's been a trial that has generated interest over time. Venetoclax has single-agent activity, but alone is not particularly durable. Whether the combination with the BTK inhibitor might not offer patients more durability is something I'm excited to see. 

I think the bispecific antibodies that are being studied in mantle cell lymphoma are very exciting. We've seen initial data from the use of glofitamab, which is now FDA-approved in diffuse large B-cell lymphoma (DLBCL). And I think those initial data tell us that there's a high response rate somewhere around 80% in patients, many of whom have had covalent BTK inhibitors.

I expect we'll see combinations of bispecifics with other agents, including potentially BTK inhibitors. These are all areas of excitement. And then we've done some work at our institution as have others on BTK degraders, so a third way of targeting BTK. Some of those trials are enrolling patients who have had both covalent BTK inhibitors and progression on non-covalent BTK inhibitors. Those trials will hopefully give us some clarity on whether there's a third way to target BTK, in patients who have already had 2 types of BTK inhibitor therapy. Lots happening and lots to look forward to.

Kami Maddocks: There is a lot of great things going on. Thank you both for those nice summaries. Maybe to end, I'll just put a little pressure on you both and ask you to tell me what you think the most exciting thing coming in mantle cell lymphoma is.

Jia Ruan: I'll take a shot. I'm very impressed with the bispecific antibody, and it seems to be very effective and some of which are having more finite duration of therapy, which is very welcoming. In fact, we look forward to seeing when that potentially can be introduced into our clinical practice and with that, in addition, to be combined with other novel agents. I'm looking forward to learning more about bispecific antibodies alone or in combination at this coming ASH.

Krish Patel: I'll echo that and say I think Dr Ruan mentioned earlier, we're increasingly looking for less toxic therapies for our patients. I think we have many therapies that have good single-agent activity, including bispecifics, including covalent, and now non-covalent, BTK inhibitors, potentially venetoclax. 

I'm excited to see what the potential rational combinations of these therapies might be in even the frontline setting to potentially give time-limited treatment without any chemotherapy to patients with mantle cell.

Kami Maddocks: Great. I'd like to thank you so much, Dr Ruan and Dr Patel. Thank you for taking the time to listen, and thank you to Oncology Learning Network for organizing this discussion.