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Future of MCL Treatment May Lie in Combinations, CAR T-Cell Therapy

Angelica Welch
Published: Wednesday, Nov 14, 2018

Robert Dean, MD

Robert Dean, MD

Experts are hard-pressed to find impactful, long-lasting treatment regimens for patients with mantle cell lymphoma (MCL). Moreover, Robert Dean, MD, said that BTK inhibitors and chimeric antigen receptor (CAR) T-cell therapy may address the unmet needs of the difficult-to-treat patient population.

“We still face the problem of these patients having a very high risk of mortality at the time that they relapse. Initial remissions and survival have improved, but what we can do for patients after they relapse still leave a lot of room for improvement,” said Dean. “We need drugs that are going to be active against the hard cases to treat—we need drugs that will work well in tandem [with BTK inhibitors].”

In an interview during the 2018 OncLive® State of the Science Summit™ on Hematologic Malignancies, Dean, a staff physician at Cleveland Clinic, discussed the promise for new therapies in MCL.

OncLive: Could you discuss the current treatment landscape of MCL?

Dean: The treatment of [patients with] MCL has evolved in a step-wise manner over the past 20 years. Studies have gradually incorporated the monoclonal antibody rituximab (Rituxan) into frontline therapy. Our approaches to frontline therapy have diverged into a more intensive route that is more appropriate for younger, fit patents who receive combination chemotherapy, followed by consolidation with high-dose chemotherapy and autologous stem cell transplant (ASCT). Now, rituximab maintenance follows that course of treatment.

On the other hand, a pathway that is appropriate for patients who are less medically fit or older involves less intensive initial chemotherapy, typically with bendamustine and rituximab, and then rituximab maintenance without consolidation with ASCT. For those respective patient groups, frontline outcomes with the sequential improvements in those approaches have continued to [improve] over the years.

A number of drugs have been approved for the treatment of patients with relapsed MCL in particular. [These include] bortezomib (Velcade) and lenalidomide (Revlimid) here in the United States, temsirolimus (Torisel) over in Europe, and more recently, the BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence) [in the United States]. Both ibrutinib and acalabrutinib appear to be more active in patients with MCL than the earlier drugs that were approved in the relapsed setting. There is a slightly higher rate of significant adverse events (AEs) with ibrutinib, particularly issues related to atrial fibrillation and bleeding—most of which are minor, but can be clinically serious. Those 2 types of toxicities are relatively rare with acalabrutinib.

We have now seen some improvement in frontline treatment over time, but also gradual improvements with the advent of these drugs for our patients in the relapsed setting. We do not yet know whether combining these drugs in new ways or moving them earlier in the treatment course can provide better outcomes and longer remissions, or prevent relapse. If you look at the activity of bortezomib with lenalidomide and compare it with the activity of ibrutinib and acalabrutinib, the 2 former drugs have already been put to the test in a large phase III trial. Everyone wants to know about testing ibrutinib or acalabrutinib upfront because, in the relapsed setting, they work better. It stands to reason that they may do more if you move them to the frontline setting. We want to see studies that test that.




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