Sequencing bispecific antibodies and CAR T cells for FL

Abstract

Treatment for relapsed/refractory (R/R) follicular lymphoma (FL) has evolved over recent years with the introduction of multiple novel immunotherapies: anti-CD3 × CD20 bispecific antibody (BsAb) T-cell engagers and anti-CD19 chimeric antigen receptor T cells (CAR T). Both drug classes are highly active, and their adverse event profiles overlap considerably, with cytokine release syndrome, cytopenias, and infections being most common. However, key differences include accessibility and logistical considerations as well as distinct neurologic toxicities, which make recommending a BsAb or CAR T a nuanced decision for each patient with R/R FL. Notably, patients could receive both classes of therapies in sequence; however, data guiding this decision are sparse. Considering the 3 most advanced agents in each class, we generally favor BsAbs before CAR T as the standard-of-care third-line treatment for the typical patient with R/R FL without concern for aggressive histologic transformation (HT). This is based on a 3-year follow-up of the mosunetuzumab phase 2 trial in R/R FL highlighting durable complete responses after a time-limited therapy with an acceptable safety profile for patients of all ages and reasonable performance status. We generally prioritize CAR T before BsAbs for patients with proven or suspected HT given the curative-potential of this approach based on trial data from R/R diffuse large B-cell lymphoma; it is unknown whether BsAbs offer the same long-term benefit in transformed FL. Overall, with the ability to personalize the sequencing of BsAbs and CAR T, the recently expanding portfolio of highly effective immunotherapies for R/R FL is poised to offer considerable benefit to this patient population.

Graphical abstract

Figure 1.

Pros and cons of bispecific antibodies vs CAR T cells for R/R FL. Made with BioRender.

Figure 2.

Steps and time to first response assessment. Key phases of care before and after BsAb or CAR T treatment from referral to first response assessment. Note that timing of CAR T could be delayed or prolonged at several points, most commonly due to insurance authorization (eg, single-payer agreement negotiations) and the need for lead-in treatment in highly symptomatic patients. PET/CT, positron emission tomography/computed tomography; PFTs, pulmonary function tests; SW, social work; TTE, transthoracic echocardiogram.