Novel Developments in the Frontline and Relapsed/Refractory Mantle Cell Lymphoma Treatment Landscape

Tycel Phillips, MD, City of Hope, Duarte, California, reviews the latest updates and developments in both the frontline and relapsed/refractory treatment landscape for patients with mantle cell lymphoma (MCL).

Transcript:

Hi, my name is Dr Tycel Phillips from City of Hope in Duarte, California. Some of the more exciting things that are in the field of mantle cell lymphoma—I think we'll start twofold. In the frontline setting, we have the TRIANGLE study that has been discussed at several meetings, which is a study that moved the BTK inhibitor ibrutinib into the frontline setting in combination with a regimen that alternated R-CHOP [rituximab with cyclophosphamide, doxorubicin hydrochloride, and vincristine sulfate] and R-DHAP [(rituximab, dexamethasone, cytarabine, cisplatin].

Patients were subsequently randomized to receive that plus auto transplant plus 2 years of maintenance, or just 2 years of ibrutinib maintenance without an auto transplant, compared to what our standard of care had been historically, which is chemotherapy followed by auto transplant. From this trial, it indicated a substantial benefit especially in patients with high-risk features with the addition of a ibrutinib to the study population. I think more exciting is that, at least early on, it did not necessarily show a benefit of auto-transplant in the patients who receive the ibrutinib.

In this situation it suggests that we can probably eliminate autologous stem cell transplantation from some patients in the frontline setting, which is very important because of the toxicity that comes from an auto-transplant, which is secondary cancers, pulmonary toxicity, and cardiac toxicity. Not to mention patients have to stay in the hospital for 10 to 14 days as we monitor, and then while they recover from the transplant complication. As we move forward we'll look for longer follow-up from this trial to support whether or not we can completely eliminate auto-transplant in the frontline setting for patients with mantle cell lymphoma.

In the relapsed/refractory setting I think CAR-T, which is chimeric antigen receptor therapy, has been the biggest thing that has come into the relapsed/refractory setting. These treatments, which are 1-term treatments that take the patient's T-cells, modify them, and infuse them back, has shown to be the first and most effective agent that we have available in the post-BTK space. Bruton’s tyrosine kinase inhibitors, or BTK inhibitors have become the mainstay of second-line therapy, but we struggle quite a bit when patients relapse on these drugs, as most of the other approved agents have very little if any durable response in this patient population.

With CAR-T, specifically with brexu-cel, we saw a very high overall response rate. There appears to be some durable progression-free survival in this patient population, which suggests that this will be a good salvage for these patients post-BTK. More recently we did have some information that came out about liso-cel, which is another CAR T-cell therapy. The biggest benefit to liso-cel that has an improved safety profile compared to brexu-cel, less neurological complications, less cytokine release syndrome. It does appear that brexu-cel [brexucabtagene autoleucel] is probably more efficacious than liso-cel [lisocabtagene maraleucel], but as we get more data, we'll hope to be able to tease out how to choose between these 2 CAR-T products, and which is best for our patients.

And then lastly, the bispecific antibodies, more specifically, glofitamab or mosunetuzumab in combination with polatuzumab, has shown to be effective at least in clinical trials. Moving forward, we would hope to see if these bispecifics will get approval in this patient space, because it'll allow us to treat these patients with these agents outside of CAR-T centers, because bispecifics don't necessarily require to be sort of fact-certified, because it's not a cellular therapy. It is an off-the-shelf antibody that functions very similar to CAR T-cell therapies and has an improved safety profile, especially in regards to neurological complications as compared to CAR-T. At least very early on, the efficacy and the duration of response of these drugs appears to be quite favorable.

We still need more long-term follow-up to see how they outwardly long -term compare to CAR-T, but at least early on these are encouraging results from these trials. As we get more indication from these drugs, these ages may move up as far as line of therapies, and may be something we can utilize in the frontline setting to improve outcomes for all patients with mantle cell lymphoma.