Evolving therapeutic landscape in follicular lymphoma: a look at emerging and investigational therapies

Abstract

Follicular Lymphoma (FL) is the most common subtype of indolent B cell non-Hodgkin lymphoma. The clinical course can be very heterogeneous with some patients being safely observed over many years without ever requiring treatment to other patients having more rapidly progressive disease requiring multiple lines of treatment for disease control. Front-line treatment of advanced FL has historically consisted of chemoimmunotherapy but has extended to immunomodulatory agents such as lenalidomide. In the relapsed setting, several exciting therapies that target the underlying biology and immune microenvironment have emerged, most notable among them include targeted therapies such as phosphoinositide-3 kinase and Enhancer of Zeste 2 Polycomb Repressive Complex 2 inhibitors and cellular therapies including chimeric antigen receptor T cells and bispecific T cell engagers. There are several combination therapies currently in clinical trials that appear promising. These therapies will likely reshape the treatment approach for patients with relapsed and refractory FL in the coming years. In this article, we provide a comprehensive review of the emerging and investigational therapies in FL and discuss how these agents will impact the therapeutic landscape in FL.

Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways

“…Three different PI3K inhibitors have been approved by the FDA for the treatment of follicular lymphoma [ 164 ]. Following a successfully phase III clinical study [ 165 ], the FDA approved the first PI3K inhibitor, Piqray (alpelisib), for breast cancer patients with advanced disease and where their tumors have the PIK3CA mutation and are hormone receptor (HR) positive and HER2 negative in 2019.…”

A multicenter phase II study of bendamustine, rituximab, and cytarabine (BRAC) for relapsed or refractory patients with follicular lymphoma or mantle cell lymphoma

“…The combination of rituximab and chemotherapy has significantly improved outcomes for B-cell non-Hodgkin lymphoma (NHL) patients. However, conventional therapies cannot cure follicular lymphoma (FL) and mantle cell lymphoma (MCL) [ 1 , 2 ]. Bendamustine has demonstrated high efficacy as monotherapy and in combination with rituximab for relapsed or refractory indolent B-cell NHL and MCL [ 3 ].…”

Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma

“…Patients with FL whose disease progresses within 2 years of initial diagnosis or whose disease is double‐refractory to both rituximab and chemotherapy also typically have a poor prognosis [ 12 ]. The poor response to immunochemotherapy seen in patients with relapsed/refractory (R/R) disease has led to considerable interest in treatment approaches based on targeted therapy combinations [ 13 , 14 ].…”