Medication Summary
The goals of pharmacotherapy are to induce cancer remission, reduce morbidity, and prevent complications.
Antineoplastics, Other
Class Summary
These agents inhibit cell growth and proliferation.
Cyclophosphamide
Cyclophosphamide has antineoplastic activity mediated by its 2 active metabolites. These metabolites are alkylating agents that prevent cell division by cross-linking DNA strands. Cyclophosphamide is absorbed almost completely from the GI tract, making it bioavailable in either oral (PO) or intravenous (IV) forms. Excretion is primarily via urine.
Doxorubicin
Doxorubicin is an anthracycline antibiotic that can intercalate with DNA, affecting many of the functions of DNA, including synthesis. This agent is administered intravenously. Doxorubicin distributes widely into bodily tissues, including the heart, kidneys, lungs, liver, and spleen. It does not cross the blood-brain barrier, and it is excreted primarily in bile.
Vincristine (Vincasar PFS)
Vincristine is a vinca alkaloid that is cell cycle specific (M phase). The mitotic apparatus is arrested in metaphase via disruption of the microtubules. Absorption of vincristine through the GI tract is variable; therefore, administer the drug intravenously. It is metabolized extensively in the liver and excreted primarily via bile. Neurotoxicity is the limiting factor during therapy. Peripheral neuropathy is vincristine's most common adverse effect at usual doses.
Etoposide (Toposar)
Etoposide is an epipodophyllotoxin that induces DNA strand breaks by disrupting topoisomerase II activity.
Cisplatin
Cisplatin is a platinum-containing compound that exerts its antineoplastic effect by covalently binding to DNA with preferential binding to 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 cytoplasmic protein. Cisplatin is a bifunctional alkylating agent that once activated to an aquated form in the cell, binds to DNA, resulting in interstrand and intrastrand cross-linking and denaturation of the double helix.
Cytarabine
Cytarabine is converted intracellularly to the active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. It is cell cycle S phase specific. Cytarabine blocks the progression from the G1 to the S phase and, in turn, kills cells that undergo DNA synthesis in the S phase of the cell proliferation cycle.
Bleomycin
Bleomycin is 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.
Carboplatin
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.
Carboplatin has the same efficacy as cisplatin but with a better toxicity profile. The main advantages over cisplatin include less nephrotoxicity and ototoxicity, thus not requiring extensive prehydration, and it is less likely to induce nausea and vomiting; however, it is more likely to induce myelotoxicity.
Ifosfamide (Ifex)
Ifosfamide binds with nucleic acids and other intracellular structures, causing cross-linking of DNA strands. It inhibits DNA and protein synthesis.
Mechlorethamine (Mustargen)
This alkylating agent is a component of the MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen.
Methotrexate (Trexall)
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, which is necessary for conversion of folate to biologically active tetrahydrofolate.
Procarbazine (Matulane)
Procarbazine is an alkylating agent that inhibits DNA, RNA, and protein synthesis. It inhibits cell replication in all phases of the cell cycle.
Polatuzumab vedotin (Polivy, polatuzumab vedotin-piiq)
CD79b-directed antibody-drug conjugate. It is indicated in combination with bendamustine and a rituximab product for treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after ≥ 2 prior therapies.
Bendamustine (Bendeka, Treanda)
Alkylating agent indicated for treatment of indolent B-cell non-Hodgkin lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen. Included as part of a regimen containing polatuzumab vedotin and rituximab.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.
Prednisone
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 is metabolized in the liver. Inactive metabolites of prednisone are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose or duration dependent.
Dexamethasone
A component of the m-BACOD regimen (methotrexate, bleomycin, doxorubicin [Adriamycin], cyclophosphamide, Oncovin, and dexamethasone), dexamethasone is a corticosteroid 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 is metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.
Methylprednisolone (Depo-Medrol, Solu-Medrol, Medrol, A-Methapred)
A component of the ESHAP regimen (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), methylprednisolone is a corticosteroid 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.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies are antibodies targeted to specific antigenic determinants. They can be specific to growth factors, cytokines, and cell surface molecules found on tumor cells.
Rituximab (Rituxan)
The rituximab antibody is a genetically engineered chimeric mouse/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and neoplastic B lymphocytes.
The most common adverse reactions to rituximab are infusion reactions, some of which are fatal. Bowel perforation has been reported with rituximab. Patients reporting abdominal pain during therapy should be evaluated for perforation of the intestinal tract.
Reactivation of hepatitis B has been demonstrated; patients at high risk for hepatitis B should be screened prior to initiation of therapy. No studies have been conducted to determine if a dose adjustment is necessary in patients with hepatic or renal dysfunction.
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.
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).
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 including DLBCL not otherwise specified, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma after ≥2 lines of systemic therapy.
Lisocabtagene maraleucel (Breyanzi)
CD19-directed CAR T-cell therapy genetically modified autologous cell immunotherapy is administered as a defined composition to reduce variability in CD8-positive and CD4-positive T cell dose. CAR binding to CD19 expressed on tumor and normal B cells induces activation and proliferation of CAR T cells, release of pro-inflammatory cytokines, and cytotoxic killing of target cells. It is indicated for adults with R/R large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. It is not indicated for h primary CNS lymphoma.
Selective Inhibitors of Nuclear Export (SINE)
Class Summary
These agents act on tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). Inhibition of XPO1 leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins (eg, c‐myc, cyclin D1), cell cycle arrest, and apoptosis of cancer cells.
Selinexor (Xpovio)
Selinexor is the first oral selective inhibitor of nuclear export (SINE) compound. It is indicated for relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, in patients previously treated with at least 2 lines of systemic therapy.
Antineoplastics, Anti-CD19 Monoclonal Antibodies
Class Summary
The monoclonal antibody binds to human CD19, a transmembrane protein expressed on surface of cells of B-lineage origin.
Loncastuximab tesirine (Zynlonta)
Indicated for adults with relapsed/refractory large-B-cell lymphoma following 2 or more lines of systemic therapy. Indication includes disuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade lymphoma.
Tafasitamab (Monjuvi, Tafasitamab-cxix)
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It is indicated, in combination with lenalidomide for the treatment of adults with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are ineligible for autologous stem cell transplant (ASCT).
Colony-Stimulating Factors Growth Factor
Class Summary
These agents can induce an increase in reticulocyte counts with a subsequent increase in hematocrit and hemoglobin levels.
Epoetin alfa (Epogen, Procrit)
Epoetin alfa 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, and its biological activity 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.
Darbepoetin alfa (Aranesp)
Darbepoetin alfa is an erythropoiesis-stimulating protein closely related to erythropoietin, a primary growth factor produced in the kidneys that stimulates the development of erythroid progenitor cells. Its mechanism of action is similar to that of endogenous erythropoietin, which interacts with stem cells to increase red blood cell production. Darbepoetin alfa differs from epoetin alfa (recombinant human erythropoietin) in that it contains 5 N-linked oligosaccharide chains, whereas epoetin alfa contains 3. Darbepoetin alfa has a longer half-life than epoetin alfa (may be administered weekly or biweekly).
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)
Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of trimethoprim/sulfamethoxazole includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Vitamins
Class Summary
Vitamins are used to correct folic acid deficiency resulting from use of folic acid antagonists.
Leucovorin
Leucovorin is used with folic acid antagonists, such as methotrexate. It is a reduced form of folic acid that does not require enzymatic reduction reaction for activation. It allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. It is an important cofactor for the enzymes used in the production of red blood cells. Leucovorin (folinic acid, which reduces adverse effects) is given on alternating days with methotrexate, until there is a 15% decline in β-HCG over 2 days.
Antidotes, Other
Class Summary
These agents counteract the toxic effects of drugs.
Mesna (Mesnex)
In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. It inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. The adult dosage is 240 mg IV at 0, 4, 8 hours after the ifosfamide or cyclophosphamide dose.
Mesna may increase warfarin effects. Mesna does not prevent hemorrhagic cystitis in all patients (monitoring for hematuria in the morning prior to ifosfamide or cyclophosphamide dose is required). It does not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide. Common adverse effects include hypotension, headache, GI toxicity, and limb pain. Mesna is a pregnancy category B drug.
Antifungals, Other
Class Summary
An antifungal may be used in the ProMACE-CytaBOM regimen. The mechanism of action may involve the inhibition of pathways (eg, enzyme, substrate, transport) that are necessary for sterol and/or cell membrane synthesis.
Ketoconazole
Imidazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death.
Antiemetics
Class Summary
Antiemetics are always prescribed before and after the administration of chemotherapy, for the prevention of chemotherapy-induced nausea and vomiting.
Ondansetron (Zofran, Zuplenz)
Ondansetron is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.
Granisetron (Kytril, Granisol)
At the chemoreceptor trigger zone, granisetron blocks serotonin centrally and peripherally on vagal nerve terminals.
Palonosetron (Aloxi)
Palonosetron is a selective 5-HT3 receptor antagonist with a long half-life (40 h). It is a selective 5-HT3 receptor antagonist that blocks serotonin peripherally and centrally. It prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and whole-body radiotherapy.
Metoclopramide (Reglan)
The antiemetic effect of metoclopramide appears to be the result of its ability to block dopamine receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system (CNS). This agent also enhances gastrointestinal motility and accelerates gastric emptying time.
Prochlorperazine (Compro)
Prochlorperazine may relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and by depressing the reticular activating system.
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Biopsy of a cervical lymph node showing infiltration with a population of large cells (B cells) consistent with diffuse large cell lymphoma.
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Computed tomography (CT) scan of the abdomen showing mesenteric and retroperitoneal adenopathy in a patient with diffuse large cell lymphoma.
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Diffuse large B-cell lymphoma. Hematoxylin and eosin stain of a lymph node biopsy sample showing a mixture of large and small cells. The architecture of the node is lost, with a diffuse pattern of involvement.
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Patient with diffuse large B-cell lymphoma with extranodal involvement. This computed tomography (CT) scan shows an enlarged spleen and liver as a result of lymphomatous involvement.
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Patient with diffuse large B-cell lymphoma with extranodal involvement (same patient as in the previous image). This patient has an enlarged spleen and liver as a result of lymphomatous involvement. Extensive retroperitoneal lymphadenopathy is also present.
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This image depicts gallium scans performed as part of a staging workup for a patient with diffuse large B-cell lymphoma. The scans show extensive hepatosplenic and multiple sites of nodal involvement with a gallium-avid tumor.
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Role of B-cell receptor signaling in promoting proliferation and survival of DLBCL. BCR is the main factor in B-cell biology, playing a key role in B-cell development, antigen-driven clonal selection, and humoral immunity. B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling pathways. All these downstream pathways are essential for the survival of B cells. PIP3 is generated as a result of BCR-dependent PI3K activation. BTK also hydrolyzes PIP2 into DAG and IP3. IP3 induces release of calcium stores from the endoplasmic reticulum. Ca and DAG activate PKC, which leads to activation of NF-k B pathyway. PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-4,5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, Forkhead box transcription factors; GSK3b, glycogen synthase 3-beta; p21, inhibitor of cyclin-dependent kinases.
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Guidelines
- Medication
- Medication Summary
- Antineoplastics, Other
- Corticosteroids
- Monoclonal Antibodies
- Antineoplastics, PI3K Delta Inhibitors
- CAR T-cell Therapy
- Selective Inhibitors of Nuclear Export (SINE)
- Antineoplastics, Anti-CD19 Monoclonal Antibodies
- Colony-Stimulating Factors Growth Factor
- Antibiotics
- Vitamins
- Antidotes, Other
- Antifungals, Other
- Antiemetics
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