Sequencing Therapies in Follicular Lymphoma Requires Multifaceted Approach

Myron Czuczman, MD

Follicular lymphoma (FL) is a slow-growing and typically asymptomatic disease, characterized by many relapses. These characteristics and the range of treatment options currently available or in development for FL may create complicated questions regarding how to best use and sequence these therapies.

Myron Czuczman, MD, chief of the Lymphoma/Myeloma Service and head of the Lymphoma Translational Research Laboratory at Roswell Park Cancer Institute addressed strategies in sequencing and effective therapeutic approaches February 20, 2015, in a session at the 19th Annual International Congress on Hematologic Malignancies.

OncLive had the opportunity to interview Czuczman in advance of the meeting, and he stressed that sequencing of agents for FL is not one-size-fits-all recipe.

“I’m not going to give [the audience] a recipe and say ‘this is how you’re going to sequence,’” said Czuczman, “You have a choice at each step.”

Currently, the most common treatment regimens for FL are rituximab with or without chemotherapy in the front line (R-CVP, R-CHOP, and R-bendamustine), rituximab or radioimmunotherapy drugs (RIT) as consolidation, and a clinical trial, chemoimmunotherapy, HDT/SCT, or RIT as salvage.

With these agents, Czuczman said a physician has the choice of a ‘gentle’ or an ‘aggressive’ approach upfront. An ‘aggressive’ approach uses rituximab with chemotherapy (CHOP or bendamustine) with or without maintenance in hopes of achieving a complete response or cure. The downfall of this approach is more toxicity upfront.

A ‘gentle’ approach uses biologic doublets or rituximab alone in hopes of controlling disease with less toxicity upfront. However, this approach is based on phase II data involving a small number of patients, making late toxicities unknown.

In either situation, treatment decisions may be different at each step and in each patient, according to Czuczman. Tumor attributes to consider include stage and bulk, FLIPI-1/FLIPI-2 scores, and grade/transformation. A physician must also consider the patient as a whole: sites of disease involvement, prior therapies, and comorbidities.

Quality of life and the toxicity of these agents also need consideration, according to Czuczman.

Rituximab, which is used in combination with several chemotherapies, itself can be associated with a higher incidence of infusional toxicity, neutropenia, infections, rash, cough, flushing, rigors, pruritus, and chest tightness, according to the agent’s label.

Idelalisib, which is approved for FL after two systemic therapies, can elicit grade 3/4 diarrhea (13%), neutropenia (27%), and increased alanine transaminase (13%), according to data from a phase II trial.

“Some of the newer drugs are giving us different side effects that we have not seen before,” Czuczman said. “We have to watch for these side effects.”

Czuczman believes that historically accepted regimens should be reviewed and retested and that new and old agents will need to be used in sequences together for now. Eventually, he said, sequences of entirely ‘new’ agents will be put into practice.

Czuczman said that every new piece of data and drug approval raises new questions regarding sequencing.

“[Sequencing] changes every time we get a new drug and get new studies out,” Czuczman said.

While the best sequence of agents in FL is unknown, Czuczman said in his final remarks, the answer looks to be an achievable goal.

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