Dr Battiwalla on the Utility of Emerging Therapies for Aggressive FL Management

“We have a fair number of ways to target CD19 through CAR T-cell therapies as well as bispecific antibodies, EZH2, and [now] BTK inhibitors.”

Minoo Battiwalla, MD, MS, director, Blood Cancer Outcomes Research, Sarah Cannon Research Institute, TriStar Medical Group, discusses how emerging therapies, such as bispecific T-cell engagers (BiTEs), EZH2 inhibitors, and BTK inhibitor combinations, contribute to the treatment of patients with aggressive variants of follicular lymphoma (FL).

Emerging therapies are transforming the management of aggressive variants of FL, a condition traditionally considered indolent but with certain subtypes that demonstrate rapid progression, often defined as progression of disease within 24 months, Battiwalla begins. These aggressive cases demand more intensive therapeutic approaches and often involve multiple lines of treatment, he says.

Historically, anti-CD19 CAR T-cell therapies, such as axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah), have been established as options for refractory cases, Battiwalla expands. However, new agents and combinations are broadening the therapeutic armamentarium, according to Battiwalla. BiTEs, like mosunetuzumab-axgb (Lunsumio), provide a novel mechanism for targeting CD20-positive B cells, he explains. The EZH2 inhibitor tazemetostat (Tazverik) has shown efficacy in both EZH2-mutated and wild-type FL and demonstrates enhanced activity when combined with lenalidomide (Revlimid) plus rituximab (Rituxan). These combinations show promise in increasing potency and simultaneously maintaining manageable toxicity, Battiwalla adds.

BTK inhibitors, such as zanubrutinib (Brukinsa), are emerging as another cornerstone in FL management, Battiwalla expands. Their potential synergy with anti-CD20 agents offers an appealing therapeutic avenue with nonoverlapping toxicities, which may improve patient outcomes and tolerability, he emphasizes, stating that these therapies expand the toolkit for addressing aggressive FL and may minimize the burden of adverse effects.

Ultimately, the goal in treating patients with advanced FL is to prolong survival, as a cure is unlikely in these disease stages, Battiwalla reports. Selecting effective combinations of emerging therapies and mitigating toxicity is critical to achieving the best outcomes for patients with aggressive FL subtypes, Battiwalla concludes.