Moving toward Nonchemotherapy-Based Approaches in Follicular Lymphoma

Nonchemotherapy-based approaches, including PI3K inhibitors and a more widespread use of allogeneic stem cell transplant, are being explored as treatments for patients with follicular lymphoma, according to Michael L. Grossbard, MD, who added that CAR T-cell therapy is also being evaluated. 

“As time has gone by, we have tried to move more toward nonchemotherapy brute force approaches to managing follicular lymphoma,” said Grossbard, a professor in the Department of Medicine, chief of the Hematology and Medical Oncology Inpatient Service at Tisch Hospital, NYU Langone Health’s Perlmutter Cancer Center.

Grossbard, who is also section chief of Hematology at NYU Langone Health’s Perlmutter Cancer Center, spoke with OncLive®, CancerNetwork®’s sister publication, about these recent developments in the field of follicular lymphoma. 

“Follicular lymphoma is easy to get into remission with a lot of the new therapies we have, but there is a continuous period of relapse. Patients are not cured with their initial therapy” Grossbard explained. “Maintenance rituximab (Rituxan) is very helpful because you can use a targeted monoclonal antibody to prolong remissions, which may not have an impact on long-term survival, but prolonging remissions for patients is really important. For a patient, not having disease means a lot-emotionally and psychologically-in terms of quality of life.”

According to Grossbard, minimal residual disease (MRD) may help measure the length of remission for a patient; however, there are no studies in follicular lymphoma that currently show that achievement of MRD is critical. 

“There are a lot of studies that have looked at MRD in follicular lymphoma. Some of those studies go back more than 20 years, which originally showed that the only modality we had to get patients to an MRD-negative state was transplant,” said Grossbard. “Now, with rituximab and other targeted therapies, we can actually achieve that MRD-negative state with more minimalist approaches.” 

Another treatment option that Grossbard highlighted were PI3K inhibitors, which are yet another targeted therapy for follicular lymphomas. 

“We understand more about B cells gone awry, which are the essence of what lymphoma is. The B-cell receptor pathway is triggered by the number of enzymes in a cascade,” Grossbard explained. “One of those [enzymes] is PI3K, and by blocking that particular enzyme, we can block the growth and proliferation of B cells and cause the killing of lymphoma cells.”

However, in order to determine which type of PI3K inhibitor a patient should receive, Grossbard indicated that there are no clear guidelines to be followed, as it depends on personal experience and comfort with the drugs. He recommends becoming familiar with 1 or more of them in order to see where they fit into a patient’s treatment course. 

For patients with heavily pretreated follicular lymphomas, Grossbard indicated that allogeneic transplant opens an option for potential cure, even in later stages and those with more advanced and refractory disease. However, this therapy option is typically not recommended unless a patient has been extensively pretreated.

“Patients who have been through multiple chemotherapy regimens, multiple biological therapy regimens, and still have a good performance status and a tolerable amount of comorbid disease would fall into that sweet spot of considering allogeneic stem cell transplant,” said Grossbard. “Still, even though we do a lot better with managing toxicities than we used to, there are significant potential adverse events of graft-versus-host disease and other complications of allogenic transplant.” 

When asked about the status of venetoclax (Venclexta) in follicular lymphoma, a BCL2 inhibitor, Grossbard suggested that there is still a lot that is unknown. Venetoclax is currently approved for use in chronic lymphocytic leukemia, small lymphocytic lymphoma, and acute myeloid leukemia. 

“In theory, venetoclax should be a marvelous drug for follicular lymphoma, but the response rates in follicular lymphoma with single-agent venetoclax have been a little more disappointing than we would have anticipated,” Grossbard said. “Venetoclax’s place in follicular lymphoma still remains to be defined.”

This article was adapted from an article that originally appeared on OncLive, titled “Follicular Lymphoma Moves Toward Chemo-Free Regimens.”