Precision Medicine and Personalized Treatments Shifting the Tide in Mantle Cell Lymphoma

While resistance can often make it a challenge to treat mantle cell lymphoma (MCL), therapies have come a long way in recent years thanks to the emergence of personalized treatment and the use of BTK inhibitors, according to Dr. Jia Ruan.

Ruan, a hematologist and oncologist from Weil Cornell Medicine in New York City, recently sat down with OncLive®, CURE®’s sister publication, to discuss the treatment trends in this disease space.

“We're moving toward precision medicine and personalized treatment (in MCL),” said Ruan. “The objective is to overcome resistance and come up with treatment plans that address the underlying disease biology and take personal factors about the patients into consideration.”

When asked about the novel agents that are currently showing promise in MCL, Ruan explained that BTK inhibitors have resulted in high overall response rates (ORRs), more complete remissions (CRs) and a lower number of side effects in this patient population.

Since the approval of Revlimid (lenalidomide) in 2013, a number of newer BTK inhibitors have been approved, with first-generation Imbruvica (ibrutinib) standing out as the top choice for many. “So far, this class of agents has the best single-agent activity in MCL to date,” explained Ruan. “For example, ibrutinib 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.”

A newer BTK inhibitor, Calquence (acalabrutinib), is considered just as effective as Imbruvica with an overall response rate of 81% and complete response in 40% of patients who took it during the phase 2 study that led to its approval. “That's quite remarkable for a single agent for patients who have relapsed/refractory MCL,” Ruan said.

The field continues to grow with the testing of new agents, including BCL-2 inhibitor, Venclexta (venetoclax), which is currently approved in chronic lymphocytic leukemia and other indolent B-cell non-Hodgkin lymphomas. “In MCL, we have data to suggest that it has promising activity as a single agent,” she said. “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.”

However, treating MCL can be challenging because of treatment resistance, explained Ruan. “All of the agents are being introduced, tested, and approved in the setting of relapsed disease,” said Ruan. “That is a big challenge for a sizable portion of patients who do not respond — maybe they have a genetic mutation that is not responsive to targeted therapy or they develop a secondary mutation in the process of being treated and then they become resistant.”

The issue of resistance is important to consider when treating MCL, according to Ruan. “We have to provide novel agents that are sensitive to the disease at every stage of the evolution and come up with additional therapies that can overcome the resistance,” she said.

In the future, Ruan predicts the shift toward precision medicine and personalized treatment will continue. “The objective is to overcome resistance and come up with treatment plans that address the underlying disease biology and take personal factors about the patients into consideration,” she said. “This is important for us to understand MCL individually.”

This precise approach would mean doing more genetic analysis to determine what type of disease is being treated in order to create a treatment plan that would provide the most benefit for the patient.

“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,” said Ruan.

“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.