A comprehensive analysis of the B-cell lymphoma treatment landscape reveals an unprecedented level of development activity, with over 295 companies actively advancing approximately 300 pipeline therapies, according to a new report from DelveInsight.
The report highlights significant momentum in clinical development, with multiple pharmaceutical companies launching pivotal trials in March 2025 that could reshape treatment paradigms for various B-cell lymphoma subtypes.
Key Clinical Trials Launched in March 2025
BeiGene has initiated a comparative study evaluating sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo in adults with relapsed/refractory mantle cell lymphoma (MCL). The trial aims to assess both efficacy and safety profiles of this novel combination.
Simultaneously, Celgene is conducting a study comparing golcadomide in combination with R-CHOP chemotherapy versus placebo with R-CHOP in previously untreated high-risk large B-cell lymphoma patients.
Hoffmann-La Roche has launched a trial comparing glofitamab in combination with polatuzumab vedotin plus R-CHP versus Pola-R-CHP alone in previously untreated CD20-positive large B-cell lymphoma patients.
Allogene Therapeutics is evaluating cemacabtagene ansegedleucel (cema-cel), an allogeneic CD19 CAR-T product, in patients with minimal residual disease (MRD) following first-line therapy for large B-cell lymphoma.
Emerging Therapeutic Approaches
The pipeline features diverse therapeutic modalities targeting B-cell lymphomas, with several innovative approaches showing promise in clinical development.
CAR-T Cell Therapies
Lisocabtagene maraleucel (Bristol Myers Squibb) is a CD19-directed CAR-T cell therapy with a 4-1BB costimulatory domain that enhances expansion and persistence of CAR-T cells. Currently in Phase III development, it has already received FDA approval for several large B-cell lymphoma indications.
Zamtocabtagene autoleucel (Miltenyi Biomedicine) represents an advancement in CAR-T therapy by targeting both CD19 and CD20 antigens. This bispecific approach aims to overcome resistance mechanisms associated with single-target therapies, particularly when tumors lose expression of one target.
MB-CART20.1 (Miltenyi Biomedicine) is an investigational CAR-T therapy engineered specifically to target CD20 protein on B-cells, currently in Phase I/II development.
Bispecific Antibodies
Glofitamab (Hoffmann-La Roche) is a CD20xCD3 T-cell engaging bispecific antibody with a novel 2:1 structural format. By simultaneously binding to CD3 on T-cells and CD20 on B-cells, it brings T-cells in close proximity to B-cells, activating the release of cancer cell-killing proteins. Currently in Phase III trials, it's being investigated both as monotherapy and in combination regimens.
Novel Targeted Therapies
NKTR-255 (Nektar Therapeutics) is a polymer-conjugated interleukin-15 receptor agonist designed to enhance the immune system's cancer-fighting capacity by boosting natural killer cells and memory CD8+ T cells. This mechanism may lead to long-term immunological memory and sustained anti-tumor response.
AVM0703 (AVM Biotechnology) works through a unique mechanism that induces production and release of endogenous bispecific gamma delta TCR+ and invariant TCR+ Natural Killer T-like cells. These immune cells target abnormal cells, including cancer cells, with a single dose triggering activation and mobilization of these specialized cells.
LBS-007 (Lin BioScience) inhibits cancer cell replication by interrupting the S phase of the cell cycle through inhibition of CDC7, a key regulator protein often upregulated in cancer cells compared to healthy cells.
Administration Routes and Molecule Types
The pipeline therapies utilize various administration routes, including intravenous, subcutaneous, oral, and intramuscular delivery. Molecule types span monoclonal antibodies, small molecules, peptides, and cell therapies, reflecting the diverse approaches being explored.
Market Implications
This robust pipeline signals significant industry investment in addressing unmet needs in B-cell lymphoma treatment. The development of dual-targeting therapies, allogeneic cell therapies, and novel immune-enhancing approaches suggests a trend toward more personalized and effective treatment options.
As these therapies progress through clinical development, healthcare providers and patients may soon have access to treatments with improved efficacy, reduced toxicity, and more convenient administration compared to current standards of care.
The advancement of these therapies could particularly benefit patients with relapsed or refractory disease, where treatment options have historically been limited and outcomes poor.
Looking Forward
The B-cell lymphoma treatment landscape is poised for significant evolution as these pipeline therapies advance through clinical development. With multiple Phase III trials underway, the next few years could see several new approvals that expand the therapeutic armamentarium for hematologists and oncologists.
The diversity of approaches being pursued—from targeted therapies to immune-enhancing treatments and cell therapies—suggests that future treatment paradigms may increasingly involve combination strategies tailored to specific disease subtypes and patient characteristics.
