Lymphoma
Lymphoma is a heterogeneous group of malignancies originating from lymphocytes, a subset of white blood cells integral to the immune system. The disease is broadly classified as a hematologic neoplasm and is characterized by the clonal proliferation of lymphoid cells, which can occur in lymph nodes, spleen, bone marrow, or extranodal sites. The pathogenesis of lymphoma involves genetic mutations, chromosomal translocations, and dysregulation of signaling pathways that govern lymphocyte growth, survival, and differentiation, often resulting from cumulative genetic insults or viral infections such as Epstein-Barr virus or human T-cell lymphotropic virus. Lymphomas can disrupt normal immune function, leading to immunodeficiency, increased susceptibility to infections, and, in aggressive forms, rapid organ dysfunction. The health impacts range from asymptomatic lymphadenopathy to systemic symptoms such as fever, night sweats, weight loss (B symptoms), and, in advanced disease, multi-organ compromise and increased mortality.
Hodgkin lymphoma (HL) is a distinct type of lymphoma characterized histologically by the presence of Reed-Sternberg cells, which are large, abnormal multinucleated lymphoid cells. HL typically arises in lymph nodes and follows an orderly spread to contiguous nodal groups. The disease often presents with painless lymphadenopathy, frequently in the cervical region, and may be associated with systemic B symptoms. HL is further subtyped into classical Hodgkin lymphoma (including nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted) and nodular lymphocyte-predominant Hodgkin lymphoma, each with unique clinical and pathological features. HL is notable for its high cure rates, especially in early-stage disease.
Non-Hodgkin lymphoma (NHL) encompasses a diverse group of lymphoid malignancies that do not exhibit Reed-Sternberg cells. NHL is classified according to cell of origin (B-cell, T-cell, or natural killer [NK]-cell), morphology, immunophenotype, and genetic features. B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma, are the most common subtypes. NHL can present with nodal or extranodal involvement and demonstrates variable clinical behavior, from indolent forms with slow progression to aggressive subtypes with rapid clinical deterioration. The clinical course, therapeutic approach, and prognosis are highly dependent on the specific histological and molecular subtype.
Diffuse large B-cell lymphoma is the most prevalent subtype of NHL, accounting for approximately 30–40% of cases. DLBCL is characterized by the diffuse proliferation of large neoplastic B lymphocytes that disrupt normal lymph node architecture. The disease often presents with rapidly enlarging masses, systemic symptoms, and may involve extranodal sites such as the gastrointestinal tract, central nervous system, or bone. DLBCL is an aggressive lymphoma but is potentially curable with appropriate therapy. Molecular subtyping (germinal center B-cell-like versus activated B-cell-like) provides prognostic and therapeutic guidance.
Follicular lymphoma is an indolent B-cell NHL subtype characterized by the neoplastic proliferation of follicle center B cells (centrocytes and centroblasts) forming nodular or follicular patterns within lymph nodes. It often presents with painless, generalized lymphadenopathy and may remain asymptomatic for years. The disease is frequently associated with the t(14;18) translocation, resulting in BCL2 overexpression and resistance to apoptosis. While initially indolent, follicular lymphoma can transform into more aggressive forms, such as DLBCL.
Mantle cell lymphoma is a relatively uncommon and typically aggressive B-cell NHL that arises from the mantle zone of lymphoid follicles. It is characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Patients often present with advanced-stage disease, including lymphadenopathy, splenomegaly, bone marrow involvement, and gastrointestinal tract infiltration. Mantle cell lymphoma has a poorer prognosis compared to other indolent lymphomas.
Peripheral T-cell lymphomas are a heterogeneous group of aggressive NHLs derived from mature T lymphocytes. These lymphomas often present with advanced disease, extranodal involvement, and systemic symptoms. Subtypes include peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma. Prognosis is generally poor due to resistance to conventional therapies and frequent relapses.
Lymphoma is among the most common hematologic malignancies worldwide, with significant geographic and demographic variation in incidence and subtype distribution. Globally, non-Hodgkin lymphoma (NHL) accounts for approximately 4% of all cancers, with an estimated 544,000 new cases and 260,000 deaths annually according to the GLOBOCAN 2020 database. Hodgkin lymphoma (HL) is less common, comprising about 10% of all lymphomas, with an annual incidence of roughly 83,000 new cases and 23,000 deaths worldwide. NHL incidence increases with age, peaking in individuals over 60 years, while HL displays a bimodal age distribution, with peaks in young adults (ages 15–35) and older adults (>55 years). Males are generally at higher risk than females for both HL and NHL. Risk factors for lymphoma include immunosuppression (e.g., HIV/AIDS, organ transplantation), autoimmune diseases, certain infections (such as EBV, HTLV-1, HCV), family history, and exposure to specific chemicals or radiation. The overall survival rates have improved over recent decades due to advances in diagnosis and therapy, though outcomes vary widely by subtype and stage at diagnosis.
The diagnosis of lymphoma involves a combination of clinical evaluation, imaging studies, laboratory tests, and histopathological examination. The diagnostic process begins with a thorough history and physical examination, focusing on lymphadenopathy, organomegaly, and systemic symptoms. Laboratory tests may reveal cytopenias, elevated lactate dehydrogenase (LDH), and abnormal liver or renal function. Imaging modalities, including computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI), are employed to assess the extent of disease and identify involved sites. Definitive diagnosis requires excisional or core needle biopsy of an affected lymph node or extranodal tissue, followed by histopathological assessment to determine morphological subtype and immunophenotyping using immunohistochemistry and flow cytometry to characterize cell lineage (B-cell, T-cell, or NK-cell) and clonality. Molecular and cytogenetic analyses, such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), are performed to detect characteristic genetic abnormalities (e.g., translocations, gene rearrangements). Staging is conducted according to the Ann Arbor system, incorporating clinical, laboratory, and imaging findings to guide prognosis and treatment. Bone marrow biopsy is often performed for staging, particularly in advanced or indolent lymphomas. Additional assessments may include lumbar puncture for central nervous system involvement and viral serology for associated infections.
Zuberitamab is utilized as a therapeutic monoclonal antibody targeting specific antigens expressed on malignant lymphoid cells, contributing to direct cytotoxicity and immune-mediated tumor cell clearance. Golidocitinib hemi-ethyl acetate solvate functions as a selective Janus kinase 1 (JAK1) inhibitor, modulating cytokine signaling pathways implicated in lymphoid malignancies and reducing pathological lymphocyte proliferation. Pirtobrutinib is an oral, highly selective, reversible inhibitor of Bruton’s tyrosine kinase (BTK), providing targeted therapy for B-cell lymphomas by disrupting B-cell receptor signaling and tumor cell survival. Actalycabtagene autoleucel represents a chimeric antigen receptor (CAR) T-cell therapy, in which a patient’s own T cells are genetically modified to express a CAR targeting lymphoma-associated antigens, enabling potent and specific cytotoxicity against malignant cells. Epcoritamab is a bispecific antibody that simultaneously binds CD3 on T cells and CD20 on B cells, thereby redirecting T-cell cytotoxicity toward malignant B lymphocytes. Glofitamab is another bispecific antibody engaging both CD20 on B cells and CD3 on T cells, designed to facilitate T-cell–mediated lysis of lymphoma cells. Sugemalimab is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1), enhancing anti-tumor immune responses by blocking inhibitory signaling in the tumor microenvironment. Valemetostat tosylate is an oral dual inhibitor of enhancer of zeste homolog 1 and 2 (EZH1/2), epigenetic regulators implicated in the pathogenesis of certain lymphomas, resulting in reactivation of tumor suppressor genes and inhibition of malignant cell growth. Mosunetuzumab is a bispecific antibody targeting CD20 and CD3, promoting T-cell–directed killing of B-cell lymphoma cells. Liposomal mitoxantrone hydrochloride is a chemotherapeutic agent encapsulated in liposomes to enhance delivery and reduce systemic toxicity, providing cytotoxic effects through DNA intercalation and inhibition of topoisomerase II, thereby inducing apoptosis in lymphoma cells.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| zuberitamab | ||||
 | golidocitinib hemi-ethyl acetate solvate (USAN) | 2 C25 H31 N9 O2 . C4 H8 O2 | 1067.251 | |
 | pirtobrutinib (Rec INN; USAN) | 2101700-15-4 | C22 H21 F4 N5 O3 | 479.427 |
| actalycabtagene autoleucel | ||||
| epcoritamab (Rec INN; USAN); epcoritamab-bysp | 2134641-34-0 | |||
| glofitamab (Rec INN; USAN); glofitamab-gxbm | 2229047-91-8 | |||
| sugemalimab (Rec INN) | 2256084-03-2 | |||
 | valemetostat tosylate (Rec INNM) | 1809336-39-7 (free base); 1809336-93-3 | C26 H34 Cl N3 O4 . C7 H8 O3 S | 660.22 |
| mosunetuzumab (Prop INN; Rec INN; USAN); mosunetuzumab axgb | 1905409-39-3 | |||
| liposomal mitoxantrone hydrochloride; liposomal mitoxantrone hydrochloride injection; mitoxantrone hydrochloride liposome injection |
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