Precision Medicine Research Aims to Overcome Resistance in Mantle Cell Lymphoma

Overcoming resistance and determining better treatment plans that address the underlying disease biology of mantle cell lymphoma (MCL) is important to better understand how to personalize treatment for patients, according to Jia Ruan, MD, PhD.

“If we could know [about mutations] ahead of time, we could have the treatment designed and tailored to maximize treatment effectiveness and minimize adverse events,” she added in an interview with OncLive, CancerNetwork’s sister publication. “It doesn't make sense to subject patients to all of the cytotoxicity associated with conventional intensive chemotherapy while other options, such as participation in clinical trials with novel agents, could be very effective.”

In particular, the use of BTK inhibitors have resulted in high overall response rates (ORRs), more complete remissions (CRs), and a lower number of adverse events (AEs) in patients with MCL. “So far, this class of agents has the best single-agent activity in MCL to date. For example, ibrutinib (Imbruvica) would give about a 65% to 67% ORR, and about 20% of that would be CRs. In contrast, lenalidomide would give you about a 30% ORR and up to about 8% CR,” said Ruan, a hematologist/oncologist at Weil Cornell Medicine.

Another BTK inhibitor, acalabrutinib (Calquence), has a narrower target spectrum, she added. As a result, the agent could cause less off-target adverse events (AEs), while being just as effective.

“…in the phase II study that led to the approval of acalabrutinib, the ORR was 81%, and over 40% of patients had a CR,” Ruan said. “That's quite remarkable for a single agent for patients who have relapsed/refractory MCL.”

In addition to BTK inhibitors, researchers are also evaluating a BCL-2 inhibitor, venetoclax (Venclexta), that has been approved to treat patients with chronic lymphocytic leukemia and other indolent B-cell non-Hodgkin lymphomas.

“Currently, it's being studied in combination with a variety of other agents, including BTK inhibitors. They seem to work very well and are helping to move treatment away from chemotherapy,” Ruan explained. 

Lastly, PI3K inhibitors have been studied, including idelalisib (Zydelig), copanlisib (Aliqopa), and duvelisib (Copiktra), but have had limited durations of response. 

Ruan noted that all of these agents are being introduced, tested, and approved in the setting of relapsed disease. 

“The treatment resistance continues to be a central issue with providing effective treatment for patients with MCL,” she added. “This is a very important issue [to consider] when treating MCL. We have to provide novel agents that sensitive to the disease at every stage of the evolution and come up with additional therapies that can overcome the resistance.

This article is adapted from an article that originally appeared on OncLive, titled “Expert Shares Insight on Precision Medicine Efforts in MCL.”