Bijal D. Shah, MD, shares the breakthroughs in the mantle cell lymphoma (MCL) treatment landscape that he found most promising at the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, including findings from the SIMPATICO and BOVen trials. 

Transcript: 

Hi, my name is Bijal Shah from the Moffitt Cancer Center in Tampa, Florida. Thanks for inviting me to share my thoughts on this year's American Society of Hematology 2023 meeting, specifically as it pertains to mantle cell lymphoma. I'm always excited when the meeting highlights the progress we're making in the space. I shared in another forum that I'm really excited to see major strides in terms of improving overall survival and duration of remissions in this disease space.

It wasn't long ago that we were talking about 2- and 3-year survivals for this disease, and now we're talking about how we extend beyond 10-year survival so that mantle cell lymphoma starts to more closely resemble follicular lymphoma. [These are] very exciting times. 

In terms of how I process some of the information from this year's meeting, I'm going to focus on 3 areas. The first is how we think about frontline therapy for mantle cell lymphoma, specifically as it relates to the integration of newer drugs. 

So, we have the updated SIMPATICO results---this is ibrutinib [plus] venetoclax versus ibrutinib [alone]. We have a study arising out of China using orelabrutinib with lenalidomide and rituximab. And, we have the BOVen trial results using zanabrutinib, venetoclax, and obinutuzumab. When you look at these, I think what we're seeing in terms of the questions that we're trying to answer is: can we target specifically higher-risk mental cell lymphoma with novel therapies and improve outcomes? Certainly, this seems to be the case looking at the BOVen [trial]---this is the zanu[brutinib], venetoclax, obinutuzumab combination, and the orelabrutinib-rituximab combinations.

It certainly seems that we're achieving that landmark. We're able to better generate remissions and patients we would otherwise consider chemo refractory, so, a high tendency for [tumor protein p53] (TP53) and high-risk mutations. With regards to ibrutinib-venetoclax data and also these other 2 trials, I think that we're also seeing the march of [Bruton tyrosine kinase inhibitors] (BTKs) in the frontline. Certainly, we saw early attempts at this with [the] SHINE [trial], with some questions about some of the toxicity of that particular combination. Now, as we start to pull bendamustine out of the mix and focus on what these pills, or these infusions, are able to accomplish, it seems like we're able to build further on that story. 

I think there are lots of encouraging things coming forward. We've got the acalabrutinib, lenalidomide, and rituximab story that is evolving. That was presented last year. We also, of course, have acalabrutinib, venetoclax, and rituximab also building steam.

So, lots of stuff to come, I think, as we talk about using novel agents in the frontline setting for mantle cell lymphoma in terms of the next piece [we ask], how are we better managing relapsed disease? I was excited by the mosunetuzumab and polatuzumab data set. Here, these are patients who are very high-risk, failing BTK inhibitors, failing [chimeric antigen receptor] (CAR) T-cell therapy in many instances, and treated with this novel combination of an antibody-drug conjugate and a bispecific, generating [complete response] (CR) rates upwards of 70% with meaningful duration of remissions upwards of a little over a year. [Progression-free survival] (PFS), again, also pushing almost a year and a half. [Overall survival] (OS) also pushes about a year and a half. 

A very meaningful combination, and I'm really hopeful to see this story build out further with other antibody drugs and bispecific combinations. As we move into the next category—I call that broad category "maintenance"—what are we doing and what are we learning?

One of the abstracts that really surprised me was the benefit of obinutuzumab over rituximab. Mantle cell lymphoma classically expresses a lot of CD20, and so I wasn't expecting there to be a big difference in terms of duration of permission or the like with the use of [obinutuzumab] over rituximab, but that's exactly what we've seen. It really seems to be a superior monoclonal for mantle cell lymphoma and, again, appears to be safe. I think now the big question is, are we going to start pivoting away from rituximab maintenance in this disease space, now that we have this pivotal frontline data? 

The other interesting observation was the use of [lenalidomide-rituximab] over rituximab. Again, another attempt to displace rituximab monotherapy or rituximab, I guess, broadly speaking, as a maintenance agent. Here, [rituximab-lenalidomide] was superior to rituximab, and I think this is important [because] we didn't see that same benefit when we use bendamustine or bendamustine-rituximab. Using less immunosuppressive regimens, we're starting to see the benefit of improved immunotherapy in this maintenance setting. 

Now, tolerability is another question. Certainly, it's been hard to incorporate [rituximab-lenalidomide], but, if this bears out, there may be opportunities for pulsing the [lenalidomide] maybe once every 3 months or something like that with novel trial designs, now potentially on obinutuzumab back up backbone, to allow us to extend disease-free remission for our patients.

Lots of very exciting data. Thanks for inviting my input. We'll see how things evolve as we go forward.

Source: 

Chen JMH, Zhang I, Wu JJ, et al. Matching-adjusted indirect comparison (MAIC) of brexucabtagene autoleucel (brexu-cel) and pirtobrutinib in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) previously treated with a covalent bruton tyrosine kinase inhibitor (cBTKi). Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 5136