Novel Therapies for Indolent Lymphomas in the Cellular Therapy Era

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Background

Indolent B-cell non-Hodgkin lymphomas (iNHLs) account for approximately 40% of all NHL cases. The majority of iNHLs are mature B-cell lymphomas, including the most common subtype of follicular lymphoma (FL), accounting for approximately 25% of all NHLs, followed by marginal zone lymphoma (MZL), approximately 8-12% of all NHLs. 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. Although the majority of patients with advanced iNHLs who require treatment are expected to have relatively good long-term outcomes based on current treatment approaches, there is still around 20% of patients who have a persistent relapsing course with very difficult to treat disease. Although chemoimmunotherapy was the mainstay for the treatment of these patients for a long time, the past decade has seen a change in the treatment paradigm in this disease group.

With a better understanding of the genetic, epigenetic, and immunological landscape, several exciting therapies targeting the underlying biology and immune microenvironment have emerged. Most notable among them include the small molecule inhibitors and cellular therapies such as CAR-T and bispecific antibodies. 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 iNHLs in the coming years including with high-risk subsets.

In this Research Topic we welcome the submissions of Review, Mini Review, Perspective, Clinical Trial, and Original Research articles on the following, and related, subtopics:

• Newer immunotherapies for indolent lymphomas (bispecific antibodies, CAR-T cell therapy, immunoconjugates)
• Small molecule inhibitors for indolent lymphomas
• Newer diagnostic strategies for indolent lymphomas
• Predictive and prognostic biomarker studies to small molecule inhibitors and immunotherapies

Note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by in vitro or in vivo functional validation are considered out of scope of this section.

Topic Editor Dr. Narendranath Epperla received an honorarium from Novartis. Topic Editor Dr. Sairah Ahmed's institution received funding from Seattle Genetics, Merck, Xencor, and Tessa Therapeutics

Keywords: FL, MZL, CAR-T cell therapy, bispecific antibodies, immunotherapies, immunoconjugates, small molecule inhibitors.

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