B-Cell Lymphoma Medication

Updated: Apr 09, 2020
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Medication Summary

The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.


Hematopoietic Growth Factors

Class Summary

These agents can induce an increase in reticulocyte counts, with a subsequent increase in hematocrit and hemoglobin levels.

Pegfilgrastim (Neulasta)

Pegfilgrastim is a long-acting filgrastim created by the covalent conjugate of recombinant granulocyte colony-stimulating factor (ie, filgrastim) and monomethoxypolyethylene glycol. As with filgrastim, it acts on hematopoietic cells by binding to specific cell surface receptors, thereby activating and stimulating the production, maturation, migration, and cytotoxicity of neutrophils.

Epoetin alfa (Epogen, Procrit)

This agent is a purified glycoprotein produced from mammalian cells modified with gene coding for human erythropoietin (EPO). Its amino acid sequence is identical to that of endogenous EPO. The biological activity of epoetin alfa mimics human urinary EPO, which stimulates division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from bone marrow into the blood stream.


Monoclonal Antibodies

Class Summary

The agents in this class target specific antigens in carcinoma cells and induce cytotoxicity.

Ibritumomab tiuxetan (Zevalin Y-90)

A murine monoclonal antibody that targets the CD20 antigen, ibritumomab tiuxetan is chelated to the radioisotopes indium-111 or yttrium-90. It is used in conjunction with rituximab to treat B-cell NHL or rituximab-refractory follicular NHL. The regimen consists of two low doses of rituximab, an imaging dose, two-three whole-body scans, and a therapeutic dose, all of which are delivered in an outpatient setting over 8 days.

Ofatumumab (Arzerra)

Ofatumumab is an anti-CD20 human monoclonal antibody that inhibits B-cell activation in early stages. It is indicated for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab.

Alemtuzumab (Lemtrada, Campath)

Alemtuzumab is a monoclonal antibody against CD52, an antigen found on B cells, T cells, and almost all chronic lymphocytic leukemia cells. It binds to the CD52 receptor of the lymphocytes, which slows the proliferation of leukocytes.

Rituximab (Rituxan)

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an immunoglobulin G1 (IgG1) kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences.



Class Summary

These drugs have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Dexamethasone (Decadron, Dexamethasone intensol)

A component of the m-BACOD (methotrexate, bleomycin, doxorubicin [Adriamycin], cyclophosphamide, Oncovin, and dexamethasone) regimen, dexamethasone is a glucocorticoid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability.

Dexamethasone is readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.

Prednisone (Prednisone Intensol, Rayos, Deltasone)

A component of several regimens, such as CHOP, prednisone is a glucocorticoid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability.

Prednisone is readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.


Antineoplastic Agents

Class Summary

These agents inhibit cell growth and proliferation and lead to cell death.

Chlorambucil (Leukeran)

Chlorambucil alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription. It is used mainly to treat indolent lymphomas, particularly chronic lymphocytic leukemia (CLL) and Waldenstrom macroglobulinemia. This agent may be preferable for elderly patients with serious comorbid medical problems who require treatment for lymphoma. It is well absorbed orally.


Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. This agent can be used alone but is mostly used as a component of multiple combination chemotherapy regimens.

Bendamustine (Bendeka, Treanda)

Bendamustine is an alkylating agent that is a bifunctional mechlorethamine derivative. It forms covalent bonds with electron-rich nucleophilic moieties that can lead to cell death. It is active against both quiescent and dividing cells and is indicated for chronic lymphocytic leukemia (CLL).


Cisplatin is a platinum-containing compound that exerts its antineoplastic effect by covalently binding to DNA, with preferential binding to the N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to cause cross-links. The platinum complex also can bind to the nucleus and to cytoplasmic protein. A bifunctional alkylating agent, once cisplatin is activated to the aquated form in the cell, it binds to DNA, resulting in interstrand and intrastrand cross-linking and denaturation of the double helix.

Doxorubicin (Adriamycin)

An anthracycline antibiotic that can intercalate with DNA, doxorubicin affects many of the functions of DNA, including synthesis. It forms DNA-cleavable complexes by interaction with topoisomerase II, which is responsible for the cytocidal activity of the drug. Doxorubicin is administered IV and distributes widely into bodily tissues, including the heart, kidneys, lungs, liver, and spleen. It does not cross the blood-brain barrier and is excreted primarily in bile. It forms an important part of multiple chemotherapeutic regimens for lymphomas, including cyclophosphamide, hydroxydaunomycin (doxorubicin), vincristine (Oncovin), and prednisone (CHOP).

Vincristine (Vincasar PFS)

The mechanism of action of vincristine is uncertain. It may involve a decrease in reticuloendothelial cell function or an increase in platelet production; however, neither of these mechanisms fully explains the effect in thrombocytopenic purpura and hemolytic-uremic syndrome. Vincristine is used in hematologic and nonhematologic malignancies. It is a component of CHOP and other regimens for lymphoma.


Fludarabine is a purine analogue that interferes with DNA synthesis by inhibiting ribonucleotide reductase. It is also incorporated into RNA, causing inhibition of RNA and protein synthesis; however, its primary effect may result from activation of apoptosis.

Nelarabine (Arranon)

Nelarabine is a prodrug of the deoxyguanosine analogue 9-beta-D-arabinofuranosylguanine (ara-G). It is converted to the active 5'-triphosphate, ara-GTP, a T-cell–selective nucleoside analog. Leukemic blast cells accumulate ara-GTP. This allows for incorporation into DNA, leading to inhibition of DNA synthesis and cell death


Cytarabine is converted intracellularly to the active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. It is cell cycle S phase specific and it blocks the progression from the G1 to the S phase, in turn killing cells that undergo DNA synthesis in the S phase of the cell proliferation cycle.

Gemcitabine (Gemzar)

Gemcitabine is a cytidine analog. It is metabolized intracellularly to an active nucleotide. It inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. It is cell-cycle specific for the S phase. Gemcitabine is indicated as first-line treatment for locally advanced (nonresectable stage II or stage III) or metastatic (stage IV) pancreatic adenocarcinoma.

Etoposide (Toposar)

Etoposide is a glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single- and double-strand DNA breaks. This causes cell proliferation to arrest in the late S or early G2 portion of the cell cycle.


Related to anthracyclines. Mitoxantrone intercalates into DNA. This results in cross-links and strand breaks. Binds to nucleic acids and inhibits DNA and RNA synthesis by template disordering and steric obstruction. Replication is decreased by binding to DNA topoisomerase II. Active through entire cell cycle.


Carboplatin is an analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to action of these drugs in the G1 and S phases. It has same efficacy as cisplatin, but with a better toxicity profile. The main advantages over cisplatin include less nephrotoxicity and ototoxicity, the lack of a need for extensive prehydration, and a smaller likelihood of inducing nausea and vomiting; however, it is more likely to induce myelotoxicity.


This agent is composed of a group of glycopeptides extracted from Streptomyces species. Each molecule has a planar end and an amine end; different glycopeptides of the group differ in their terminal amine moieties. The planar end intercalates with DNA, while the amine end facilitates oxidation of bound ferrous ions to ferric ions, thereby generating free radicals, which subsequently cleave DNA, acting specifically at purine-G-C-pyrimidine sequences.

Vorinostat (Zolinza)

Vorinostat is a histone deacetylase (HDAC) inhibitor. HDAC inhibition results in hypoacetylation of core nucleosomal histones, it condenses the chromatin structure, and it represses gene transcription. It is indicated for the treatment of progressive, persistent, or recurrent cutaneous T-cell lymphoma.

Belinostat (Beleodaq)

Belinostat is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibiting this action induces cell cycle arrest and/or apoptosis.


Antineoplastics, Tyrosine Kinase Inhibitor

Class Summary

Ibrutinib received accelerated approval from the FDA for marginal zone lymphoma following analysis of phase 2 data in 63 patients who had a median follow-up of 19.4 months. Of these patients, 3% (n=2) treated with ibrutinib achieved complete responses (CR) and 45% (n=27) achieved partial responses (PR). Overall, 78% of patients experienced tumor reduction. Median progression-free survival was 14.2 months. [29]

Ibrutinib (Imbruvica)

Bruton’s tyrosine kinase (BTK) inhibitor forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways.

BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. It is indicated for mantle cell lymphoma in patients who have received at least 1 previous therapy. It also indicated for marginal zone lymphoma (MZL) in patients who require systemic therapy and have received at least 1 prior anti-CD20-based therapy.


Antineoplastics, PI3K Delta Inhibitors

Class Summary

This drug class inhibits one or more of the phosphoinositide 3-kinase enzymes, which are part of the PI3K/AKT/mTOR pathway, an important signalling pathway for many cellular functions such as growth control, metabolism and translation initiation. Within this pathway there are many components, inhibition of which may result in tumor suppression.

Copanlisib (Aliqopa)

Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. By inhibiting several key cell-signaling pathways may induce apoptosis and inhibition of proliferation of premalignant B cells and in turn cause tumor cell death. It is indicated for relapsed follicular lymphoma (FL) in patients who have received at least 2 prior systemic therapies.

Idelalisib (Zydelig)

Idelalisib induces apoptosis and inhibits proliferation in cell lines derived from malignant B cells and in primary tumor cells; also inhibits several cell- signaling pathways, including B cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B cells to the lymph nodes and bone marrow. It gained accelerated approval by the FDA (ie, confirmatory clinical trials in progress) in July 2014 for relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies.


Antineoplastics, Angiogenesis inhibitor

Class Summary

These agents antagonize or inhibit the development of new blood vessels.

Lenalidomide (Revlimid)

Thalidomide analogue; inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells. Indicated for in combination with rituximab product for the treatment of previously treated follicular lymphoma or marginal zone lymphoma.


PD-1/PD-L1 Inhibitors

Class Summary

Monoclonal antibodies that bind the programmed cell death-1 protein (PD-1) ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production.

Pembrolizumab (Keytruda)

Indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.


CAR T cell Therapy

Class Summary

Chimeric antigen receptor (CAR) T cell therapy is a form of adoptive T-cell therapy in which T cells are genetically engineered to express a CAR. CAR T cells preparation begins with obtaining a blood sample from the patient. The CAR molecule is introduced into the patient’s T cells through viral or nonviral approaches. The cells undergo a brief round of expansion in the laboratory and are then infused back into the patient. T cells become activated when they recognize the target antigen on the surface of the tumor, in this case, CD19. When T cells are activated, they undergo massive expansion in the body. The cells start to produce multiple different cytokines and proliferate. These cytokines improve the T cells’ function, help them traffic to the tumor site, and start killing the tumor cells by expressing cytotoxic molecules (eg, granzymes and perforins).

In October 2017, the FDA approved axicabtagene ciloleucel (Yescarta) for large B-cell lymphoma after at least two other kinds of treatment have failed. Axicabtagene ciloleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.

FDA approval was based on results from the ZUMA-1 study, an open-label, multicenter trial enrolling 111 patients from 22 institutions. Patients in ZUMA-1 received the target dose of axicabtagene ciloleucel (2 x 106 cells/kg) after low-dose conditioning with cyclophosphamide and fludarabine for 3 days. The modified intention-to-treat population involved 101 patients who received axicabtagene ciloleucel. In adults with relapsed/refractory DLBCL, the response rates were approximately 60-80%, with complete responses seen in 40-70% of patients. Following axicabtagene ciloleucel, 40% of patients maintained their complete response at six-month follow-up. The trial had a median survival follow-up of 8.7 months. [30]

In May 2018, a second CAR T-cell therapy, tisagenlecleucel (Kymriah), was approved for adults with relapsed or refractory DLBCL who are ineligible for or relapsed after ASCT. Approval was based on the single-arm, open-label, multicenter, phase 2 JULIET trial in adults with relapsed or refractory DLBCL and DLBCL after transformation from follicular lymphoma. Eligible patients must have been treated with at least 2 prior lines of therapy, including an anthracycline and rituximab, or relapsed following ASCT. Patients received a single infusion of tisagenlecleucel following completion of lymphodepleting chemotherapy. The ORR for the 68 evaluable patients was 50% (95% CI: 37.6, 62.4) with a CR rate of 32% (95% CI: 21.5, 44.8). With a median follow-up time of 9.4 months, the duration of response (DOR) was longer in patients with a best overall response of CR, as compared to a best overall response of partial response (PR). Among patients achieving CR, the estimated median DOR was not reached (95% CI: 10.0 months, not estimable [NE]). The estimated median response duration among patients in PR was 3.4 months (95% CI: 1.0, NE). [31, 32]


Axicabtagene ciloleucel (Yescarta)

CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following the binding anti-CD19 CAR T cells with target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades which eventually leads to killing of CD19-expressing cells. It is indicated for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Tisagenlecleucel (Kymriah)

CD19-directed genetically modified autologous T-cell immunotherapy that involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. It is indicated in adults with relapsed or refractory large B-cell lymphoma (r/rDLBCL) including DLBCL not otherwise specified, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma after ≥2 lines of systemic therapy.