Lori A. Leslie, MD

Lori A. Leslie, MD, lymphoma attending, John Theurer Cancer Center, discusses the approval of tazemetostat in the follicular lymphoma setting and the data that that led to its FDA approval.

Leslie says that tazemetostat is an oral EZH2 inhibitor. The first designation for this agent was in epithelioid sarcoma in January 2020. On June 18, 2020, tazemetostat was approved for use in patients with relapsed or refractory follicular lymphoma (FL).

Although there is activity with this agent in both 

 wild-type FL, the label is for patients with relapsed/refractory disease with an 

 mutation or who have no other appropriate options. Because of this indication, there's some room in terms of the label based on the data that led to the approval, according to Leslie.

The results used for the approval were from a multicenter phase 2 trial that looked at the use of this agent in 99 patients. Leslie explains that one cohort enrolled patients with 

-mutant relapsed/refractory FL, and the other was made up of patients with 

 wild-type disease. The dosing for tazemetostat was 800 mg twice a day until patients experienced disease progression or unacceptable toxicity.

In terms of the primary end point of the trial, the objective response rate in patients with 

-mutant disease was higher, at 69%, according to Leslie. Twelve percent of patients achieved complete remission. There was also activity with this drug in those with EZH2 wild-type disease; for this cohort, the objective response rate was 34%, with a complete remission rate of 4%.

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Lori A. Leslie, MD, discusses the approval of tazemetostat in the follicular lymphoma setting and the data that that led to its FDA approval.

Exploring the Tazemetostat Approval in R/R Follicular Lymphoma

Lori A. Leslie, MD, lymphoma attending, John Theurer Cancer Center, discusses the current treatment options for patients with mantle cell lymphoma (MCL).

MCL is a very complicated lymphoma, Leslie says. In the upfront setting, physicians should consider factors like age, comorbidities, and what is driving the lymphoma, such as a P53 abnormality. The treatment options in this setting include high-dose chemotherapy and autologous stem cell transplant.

For patients with MCL who are older and less fit, options include bendamustine/rituximab (Rituxan)-like regimens. In a rare subset of patients with MCL, the watch and wait approach could be appropriate, but this is less common in MCL than in other indolent lymphomas.

Overall, Leslie says that she encourages participation in clinical trials for MCL. There are many ongoing studies right now evaluating novel agents, BTK inhibitors, BCL2 inhibitors, combination regimens, and more.

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Lori A. Leslie, MD, discusses the current treatment options for patients with mantle cell lymphoma.

Expert Reviews Treatment Landscape for Patients With Mantle Cell Lymphoma

Lori A. Leslie, MD, a medical oncologist at the John Theurer Cancer Center, discusses options for patients with relapsed/refractory mantle cell lymphoma (MCL).

Leslie says that this setting is rapidly evolving in a good way with many new targeted therapies, including cellular therapy entering as a treatment option. Usually the most important choice when a patient comes in with relapsed/refractory disease depends on what they received in the frontline setting and the length of their remission. If she had a patient who had already received chemoimmunotherapy and transplant and had a 10-year remission, she would treat them differently than a patient who was given chemoimmunotherapy and relapsed while still on maintenance treatment.

For a patient with relapsed MCL, whether they are higher-risk or not, the standard of care is to consider targeted therapies. This includes Bruton kinase inhibitors (BTK), venetoclax (Venclexta), lenalidomide (Revlimid) with rituximab (Rituxan), and bortezomib (Velcade)-based therapies. Bortezomib is not as preferred now that BTK inhibitors are available, according to Leslie.

Patients who have experienced multiple relapses have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy; Leslie thinks this is one of the most exciting things in that space at the moment. The recent data looking at this type of agent in patients with relapsed MCL who are resistant or refractory to BTK inhibitors have shown a high overall response rate and about two-thirds of patients achieving complete responses that seem durable.

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Lori A. Leslie, MD, discusses options for patients with relapsed/refractory mantle cell lymphoma.

Discussing How to Treat Patients With Mantle Cell Lymphoma

Lori A. Leslie, MD, a lymphoma oncologist at the John Theurer Cancer Center at Hackensack University Medical Center, discusses chimeric antigen receptor (CAR) T-cell therapy as a treatment for diffuse large B-cell lymphoma (DLBCL) and the positive results demonstrated for this agent in patients with relapsed/refractory disease.

This is an exciting space, Leslie says. CAR T-cell therapies have shown long-term remissions of about 40%. Leslie is particularly interested in the mechanisms of resistance because even though CAR T-cell therapies are effective, she wants to know why certain patients are progressing or having a lack of response. This may be because of the loss of CD19 or different CD19 epitopes, Leslie suggests.

Further development of CAR T-cell therapy will bring up other questions, such as what other therapies can be combined with it and how we can create different targets for CAR T-cell therapy in order to increase efficacy and produce more long-term complete responses, according to Leslie.

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Lori A. Leslie, MD, discusses chimeric antigen receptor T-cell therapy as a treatment for diffuse large B-cell lymphoma and the positive results demonstrated for this agent in patients with relapsed/refractory disease.

Lori A. Leslie, MD | Authors

Articles

Exploring the Tazemetostat Approval in R/R Follicular Lymphoma

Expert Reviews Treatment Landscape for Patients With Mantle Cell Lymphoma

Discussing How to Treat Patients With Mantle Cell Lymphoma

Questioning Future Combinations and Targets for CAR T Cell in DLBCL