Adult T-cell lymphoma is a rare type of non-Hodgkin lymphoma (NHL) that affects T lymphocytes and natural killer (NK) cells. They are a group of heterogeneous malignancies that account for 12% of all NHL cases. The 5-year relative survival rate overall for patients with NHL is 69.1%; however, these rates vary depending on the T-cell lymphoma subtype.1 

This review will discuss treatment recommendations for adult T-cell lymphoma as outlined in the National Comprehensive Cancer Center (NCCN) Panel guidelines.2 NCCN provides guidance for several types of adult T-cell lymphomas. This article will offer an overview of each subtype, excluding peripheral T-cell lymphomas and the pharmacologic recommendations from NCCN. A discussion of cutaneous T-cell lymphomas will also be included.3 

The following adult T-cell lymphoma subtypes will be reviewed:

  • T-cell large granular lymphocytic leukemia
  • T-cell prolymphocytic leukemia
  • Extranodal NK/T-cell lymphoma
  • Primary cutaneous anaplastic large cell lymphoma
  • Lymphomatoid papulosis
Scaly erythematous patches on the chest and abdomen indicative of mycosis fungoides, the most common subtype of primary cutaneous T-cell lymphoma.
Figure. Scaly erythematous patches on the chest and abdomen indicative of mycosis fungoides, the most common subtype of primary cutaneous T-cell lymphoma.

T-Cell Large Granular Lymphocytic Leukemia

Large granular lymphocytic (LGL) leukemia is a rare lymphoproliferative disorder that affects T cells and NK cells. The most common subtype is T-cell LGL leukemia (T-LGL leukemia), which accounts for approximately 85% of cases; the NK subtype accounts for 10% of cases. LGL leukemia is primarily seen in older patients, with a median age at diagnosis of 66.5 years.4 

First-Line Therapies

Due to the rarity of T-LGL leukemia, there is a paucity of clinical trials to inform treatment recommendations. NCCN notes that their recommendations are based on retrospective studies. 

Common first-line treatments for T-LGL leukemia include5:

  • Low-dose oral cyclophosphamide (50-100 mg/d) ± corticosteroids
  • Oral cyclosporine (50-100 mg/d)
  • Low-dose oral methotrexate (10-15 mg/wk) ± corticosteroids 

If a patient has a concomitant active autoimmune disease, treatments should target immune system activity. Methotrexate may be useful in these patients. For those with anemia, cyclophosphamide or cyclosporine may be more suitable. NCCN recommends restricting oral cyclophosphamide treatment to 4 months if the patient does not improve due to an increased risk of mutagenesis, bladder toxicity, and leukemogenesis.2 

A response assessment should be performed after 4 months of treatment. Patients with a partial or complete response should continue treatment. If a patient does not respond to first-line treatment, NCCN recommends using another first-line treatment option. Studies show that patients whose T-LCL leukemia does not respond to methotrexate may have a response to cyclophosphamide or cyclosporine.2 

Second-Line Therapies

If all first-line treatment options fail to induce a partial or complete response, NCCN recommends the patient enroll in a clinical trial. Purine analogs including cladribine, fludarabine, and pentostatin have also shown some efficacy for T-LGL leukemia in small case reports and series.2 

Alemtuzumab is no longer commercially available due to the increased risk of infusion-related reactions, autoimmunity, and secondary malignancies. However, it may be obtained for clinical use through restricted distribution under a risk evaluation mitigation strategy (REMS) program use. Patients should be monitored for infections and cytomegalovirus reactivation while using alemtuzumab. 

T-Cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell leukemia that often has a poor prognosis.6 It is an aggressive cancer that progresses rapidly, and patients often experience symptoms at the time of presentation. T-PLL involves several areas of the body, including the lymphatic system, bone marrow, skin, and central nervous system. 

NCCN recommends that, based on the poor prognosis associated with T-PLL, patients initially enroll in a clinical trial. For those with symptomatic disease, the preferred first-line therapy for T-PLL is single-agent intravenous (IV) alemtuzumab. Dosing should be gradually escalated to 30 mg/wk to limit infusion-related reactions.7 

Patients with bulky disease, hepatic involvement, or splenomegaly are advised to undergo sequential therapy with fludarabine, cyclophosphamide, and mitoxantrone (FCM), followed by alemtuzumab maintenance.8 Dosing of FCM begins with 2 cycles in the following schedule:

  • Fludarabine 25 mg/m2 IV on days 1-3
  • Cyclophosphamide 200 mg/m2 on days 1-3
  • Mitoxantrone 8 mg/m2 IV on day 1

After restaging, patients who demonstrate a response to FCM may receive an additional 2 cycles for a total of 4 cycles. They can then start alemtuzumab within 1 to 3 months of completing FCM treatment. Patients who experience disease progression or who had stable disease may start alemtuzumab treatment immediately.

NCCN does not offer any official treatment recommendations for relapsed/refractory T-PLL due to the lack of clinical trial data. Alternate regimens that may prove effective include remaining first-line treatments not initially used, pentostatin, and alemtuzumab ± pentostatin.2

Adult T-Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is another type of lymphoproliferative neoplasm affecting T cells. ATLL is rare in the United States, accounting for approximately 2% of all T-cell lymphoma cases. ATLL is much more prevalent in Asia, particularly in Japan.2,9 ATLL is caused by infection with the human T-lymphotropic virus 1 (HTLV-1); the antiviral therapy zidovudine is crucial to controlling disease in symptomatic patients. 

There are 4 subtypes of ATLL: smoldering (10%), chronic (10%), acute (60%), and lymphoma (20%). The acute subtype of ATLL is aggressive and associated with rapid disease progression, leading to one of the poorest prognoses of all NHL types.2,9 

NCCN notes there currently are no optimal standard treatments for ATLL due to the lack of data. Patients are advised to enroll in a clinical trial. The subtype ultimately defines which regimens should be used, with information derived from small case series or reports. 

First-Line Therapies

Smoldering and chronic subtypes of ATLL typically do not require treatment and may be managed by watching and waiting until the patient begins experiencing symptoms. Patients with acute ATLL may be treated with high-dose zidovudine (750 mg/m2 twice daily) and interferon alfa (5 to 10 million units twice daily).10 However, this treatment is not recommended for patients with the lymphoma subtype, and combination chemotherapy is preferred instead for those patients. The duration of initial treatment is 2 months. 

There is insufficient research to provide data on an optimal chemotherapy regimen for the acute lymphoma subtype of ATLL. Recommendations from NCCN are outlined in Table 1. 

Table 1. Chemotherapy Regimens for Acute Subtype of ATLL

RegimenDosingDuration of Treatment 
Dose-adjusted EPOCHEtoposide 50 mg/m2/d, vincristine 0.4 mg/m2/d, and doxorubicin 10 mg/m2/d given as a 96-h infusion on days 1-4, followed by cyclophosphamide 750 mg/m2 IV on day 5 and prednisone 60 mg/m2 orally on days 1-5Treat for 21- or 28-d cycles for a minimum of 2 and maximum of 6 cycles 
CHOEPPrednisone 100 mg orally on days 1-5; doxorubicin 50 mg/m2 IV, vincristine 2 mg/m2 IV, and cyclophosphamide 750 mg/m2 IV on days 1-5; etoposide 100 mg/m2 IV on days 1 to 3None indicated

CHOEP = cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone; EPOCH = etoposide, prednisone, vincristine; cyclophosphamide, and doxorubicin; IV = intravenous.

From Ratner et al11 and Pfreundschuh et al.12

Patients with CD30-positive ATLL should undergo treatment with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone. The ECHELON-2 trial evaluated the following dosing schedule13:

  • Cyclophosphamide 750 mg/m2 IV and doxorubicin 50 mg/m2 IV on day 1 of each cycle, and
  • Prednisone 100 mg/d orally on days 1-5 of each cycle, followed by
  • Brentuximab vedotin 1.8 mg/kg on day 1 of each cycle. 

Second-Line Therapies

Patients with chronic or smoldering ATLL are advised to try combination chemotherapy regimens listed for acute and lymphoma subtypes. Patients with acute ATLL that has not responded to first-line treatment may receive an alternative treatment not previously used.2 

NCCN notes there are no optimal second-line therapies established with the support of clinical data. Preferred regimens listed in the treatment guidelines are based on institutional preferences. NCCN recommends that patients with relapsed/refractory ATLL enroll in a clinical trial as a first treatment option. 

Second-line single-agent treatments for ATLL include2:

  • Brentuximab vedotin (for patients with CD30-positive ATLL)
  • Lenalidomide
  • Mogamulizumab-kpkc

Second-line combination therapies for ATLL include2:

  • ESHAP (etoposide, methylprednisolone, and cytarabine) plus platinum-based chemotherapy (oxaliplatin or cisplatin)
  • ICE (ifosfamide, carboplatin, and etoposide)
  • GVD (gemcitabine, vinorelbine, and liposomal doxorubicin)
  • GDP (gemcitabine, dexamethasone, and cisplatin)
  • DHA (dexamethasone and cytarabine) plus platinum-based chemotherapy (carboplatin, cisplatin, or oxaliplatin)
  • GemOx (gemcitabine and oxaliplatin)

Extranodal NK/T-Cell Lymphomas

Extranodal NK/T-cell lymphomas (ENKL) are a rare type of NHL that affects the nasal passages. Patients may present with nasal bleeding caused by a mass or obstruction.14 Extranasal presentation is associated with more aggressive disease and poorer prognosis. Recent studies have determined that non-anthracycline treatment regimens have helped to significantly improve survival among patients with ENKL. 

Because ENKL are so rare, patients should be encouraged to enroll in a clinical trial or seek treatment at centers with knowledge and experience in treating ENKL. Currently, there is insufficient data to establish standardized therapies for ENKL. Treatment recommendations are based on the results of small prospective studies and retrospective analyses.2 

Induction Therapy

Conventional anthracycline-based chemotherapy regimens are ineffective in treating ENKL due to increased expression of P-glycoprotein. NCCN recommends asparaginase-based or pegaspargase-based chemotherapy regimens in place of conventional treatments. Combination therapies with radiation therapy and chemotherapy have proven to be the most effective option for treating ENKL.2 

Patients with stage I or II nasal disease are advised to undergo induction therapy with a combination of chemotherapy and radiation therapy (Table 2). 

Table 2. Induction Chemoradiation Regimens for ENKL

RegimenDosingDuration of Treatment
Concurrent radiation therapy and DeVICDexamethasone 40 mg/d, etoposide 100 mg/m2, and ifosfamide 1.5 mg/m2 on days 1-3, and carboplatin 300 mg/m2 on day 1Cycle every 21 d
Concurrent radiation therapy and VIPDRadiation therapy and cisplatin 30 mg/m2 weekly for 3-5 wk
Once initial therapy is completed, treat with etoposide 100 mg/m2, ifosfamide 1200 mg/m2, and cisplatin 33 mg/m2 on days 1-3 and dexamethasone 40 mg on days 1-4		3 cycles total
Sequential chemoradiation with modified SMILE regimenMethotrexate 2000 mg/m2 IV on day 1; dexamethasone 40 mg/d IV, ifosfamide 1500 mg/m2 IV, and etoposide 100 mg/m2 on days 2-4; pegaspargase 1500-2500 IU/m2 IV or IM on day 8Cycle every 21 d for 2-4 cycles total followed by chemoradiation
Sandwich chemoradiation with P-GemOxGemcitabine 1000 mg/m2 on days 1 and 8; oxaliplatin 130 mg/m2 on d 1; pegaspargase 2000-2500 U/m2 IM
Follow with radiation therapy, then treat with P-GemOx regimen again		Initial P-GemOx treatment for 2 cycles, followed by radiation therapy; then treat with 2-4 more cycles of P-GemOx

DeVIC = dexamethasone, etoposide, ifosfamide, and carboplatin; IM = intramuscular; IV = intravenous; P-GemOx = pegaspargase, gemcitabine, and oxaliplatin; SMILE = methotrexate, dexamethasone, ifosfamide, etoposide, and pegaspargase; VIPD = etoposide, ifosfamide, cisplatin, and dexamethasone.

From Hatayama et al,15 Kim et al,16 Qi et al,17 and Yan et al.18

Patients with stage IV nasal disease and stages I to IV extranasal disease are advised to receive combination pegaspargase-based (chemotherapy) regimens. Examples include:

  • Modified SMILE for 4 to 6 cycles;
  • P-GemOx; and
  • 6 cycles of DDGP (gemcitabine 800 mg/m2 IV on days 1 and 8, cisplatin 20 mg/m2 IV on days 1-4, dexamethasone 15 mg/m2 IV on days 1-5, and pegaspargase 2500 IU/m2 intramuscularly on day 1), cycled every 21 days.19

In cases of relapsed/refractory ENKL, clinical trials are recommended following first-line pegaspargase regimens. Studies show that monoclonal antibodies targeting programmed death-1 (PD-1) are effective for treating relapsed/refractory disease. Nivolumab and pembrolizumab are recommended as single-agent therapies.20,21 

The chemotherapy regimen GDP is also effective for relapsed/refractory ENKL and is associated with low toxicity.22 Dosing on a 21-day cycle is as follows:

  • Gemcitabine 1000 mg/m2 IV on days 1 and 8;
  • Dexamethasone 20 mg/d orally on days 1 to 4 and 11 to 14; and
  • Cisplatin 25 mg/m2 on days 1 to 3.

Patients with CD30-positive relapsed/refractory ENKL may benefit from treatment with brentuximab vedotin. However, the efficacy of this agent has only been studied in small case reports. 

Cutaneous T-Cell Lymphomas

Primary cutaneous CD30+ T-cell lymphoproliferative disorders encompass a spectrum of diseases. The most common is primary cutaneous anaplastic large cell lymphoma (ALCL), which represents approximately 8% of cutaneous lymphomas. This subtype is often indolent in nature, and patients have an excellent prognosis, even with cutaneous relapses. 

Lymphomatoid papulosis — a benign collection of lymphocytes that form skin nodules — accounts for 12% of cutaneous T-cell lymphomas. The nodules may become necrotic if untreated.3,23 

Primary Cutaneous Anaplastic Large Cell Lymphoma

Patients with primary cutaneous ALCL who are asymptomatic may be managed with observation and do not require treatment.  Solitary lesions are treated with surgical excision with or without radiation therapy.3 

Multifocal lesions are treated with systemic therapies, including brentuximab vedotin or multiagent chemotherapy with CHOP or CHOEP with or without radiation therapy. The US Food and Drug Administration (FDA) has also approved brentuximab vedotin in combination with CHP based on outcomes from the ECHELON-2 trial.3,13 

Relapsed or refractory primary cutaneous ALCL may be treated with the same regimen used previously. NCCN also recommends that patients enroll in a clinical trial for an experimental treatment.3

Lymphomatoid Papulosis

Patients with asymptomatic lymphomatoid papulosis are managed with observation. Those with limited disease may be treated with phototherapy or topical steroids. Systemic therapy is only necessary for patients with extensive lesions. Although low-dose methotrexate effectively clears skin symptoms of lymphomatoid papulosis, rapid recurrence is common following treatment.3 

Patients using topical corticosteroids should be monitored for any adverse side effects, including skin atrophy and bruising. The dose of topic corticosteroid should be tapered based on the patient’s initial response to an appropriate maintenance dose.3 Patients should undergo regular skin evaluations during and after treatment to monitor for second lymphoid malignancies. 

Monitoring Side Effects, Adverse Events, and Drug-Drug Interactions

Chemotherapy agents work by inhibiting DNA synthesis and replication to target rapidly dividing cells. Although these effects are beneficial for treating malignancies, including adult T-cell lymphomas, they are also responsible for numerous off-target effects and unwanted toxicities. Patients on a chemotherapy regimen should be monitored for common adverse events and given appropriate treatments to manage them. 

Antiemetic agents may be used to treat nausea and vomiting. Corticosteroids, antihistamine therapy, and epinephrine are recommended to treat infusion-related or allergic reactions. Liver function tests and complete blood count should be performed regularly to monitor for changes in liver enzymes or blood cell counts. If a patient experiences a severe adverse event, reduce the dose or discontinue therapy, as appropriate. 

Table 3. Side Effect Profiles of Chemotherapy for T-Cell Lymphoma

DrugMost Common Adverse EventsDrug-Drug InteractionsSpecial Population Considerations
CarboplatinAbdominal pain, back pain, constipation, cough, decreased appetite, diarrhea, fatigue and weakness, pyrexia, headache, joint pain, musculoskeletal pain, nausea, rash, upper respiratory infection, vomiting
Warnings: Infusion-related reactions		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients
CisplatinIncreased risk of infection, myelosuppression, nausea, peripheral neuropathy, pyrexia, vomiting
Warnings: Anaphylaxis, infusion-related reactions, nephrotoxicity, ocular toxicity, ototoxicity, secondary leukemia		Nephrotoxic or ototoxic drugsMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in patients with renal impairment
CyclophosphamideAlopecia, diarrhea, febrile neutropenia, nausea, neutropenia, pyrexia, vomiting
Warnings: Cardiotoxicity, immunosuppression, increased risk of serious infections, myelosuppression, pulmonary toxicity, renal toxicity, urinary tract toxicity, veno-occlusive liver disease		ACE inhibitors, G-CSF/GM-CSF, protease inhibitors, amiodarone, anthracyclines, azathioprine, busulfan, cytarabine, indomethacin, natalizumab, pentostatin, thiazide diuretics, trastuzumab, zidovudineMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in patients with hepatic and renal impairment
CyclosporineGum hyperplasia, hirsutism, hypertension, renal dysfunction, tremor
Warnings: Hepatotoxicity, hyperkalemia, nephrotoxicity, neurotoxicity, polyomavirus infections, secondary malignancies, serious infections, thrombotic microangiopathy		Drugs that may potentiate renal complications: Amphotericin B, azapropazone, cimetidine, ciprofloxacin, colchicine, diclofenac, fibric acid derivatives, gentamicin, ketoconazole, melphalan, methotrexate, naproxen, ranitidine, sulindac, tacrolimus, tobramycin, trimethoprim with sulfamethoxazole, vancomycin
Drugs that may increase cyclosporine concentrations: Allopurinol, amiodarone, azithromycin, bromocriptine, clarithromycin, colchicine, danazol, diltiazem, erythromycin, fluconazole, imatinib, itraconazole, ketoconazole, methylprednisolone, metoclopramide, nefazodone, nicardipine, oral contraceptives, quinupristin/dalfopristin, verapamil, voriconazole		May be harmful to fetus; avoid using in breastfeeding patients; use with caution in elderly patients 
CytarabineAbnormal gait, back pain, confusion, constipation, fatigue, headache, nausea, pyrexia, vomiting, weakness
Warnings: Chemical arachnoiditis, convulsions, neurotoxicity		Use caution when administering other cytotoxic agents intrathecally May be harmful to fetus; avoid using in breastfeeding patients
DoxorubicinAnorexia, constipation, decreased blood cell count, diarrhea, fatigue and weakness, hand-foot syndrome, nausea, pyrexia, rash, stomatitis, vomiting
Warnings: Cardiomyopathy, neutropenia, thrombocytopenia		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in patients with hepatic impairment
EtoposideAbdominal pain, constipation, dysphagia, nausea, neutropenia, pyrexia, vomiting
Warnings: Anaphylaxis, leukemias, myelosuppression, optic neuritis, secondary leukemias		WarfarinMay be harmful to fetus; avoid using in breastfeeding patients
FludarabineAnorexia, chills, fatigue, infection, malaise, myelosuppression, nausea, pyrexia, vomiting, weakness
Warnings: Fatal autoimmune hemolytic anemia, severe myelosuppression, trilineage bone marrow hypoplasia or aplasia		PentostatinMay be harmful to fetus; avoid using in breastfeeding patients
GemcitabineCytopenias, dyspnea, elevated liver enzymes, nausea, proteinuria, rash, vomiting
Warnings: Hepatotoxicity, infusion-related reactions, pulmonary toxicity, radiation toxicity, renal toxicity		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in patients with renal or hepatic impairment
IfosfamideAlopecia, cytopenias, hematuria, infection, nausea, vomiting
Warnings: CNS toxicity, cardiotoxicity, myelosuppression, neurotoxicity, pulmonary toxicity, secondary malignancies, serious infections, urotoxicity, veno-occlusive liver disease		CYP3A4 inhibitors and inducersMay be harmful to fetus; avoid using in breastfeeding patients; adjust dosing and monitor in geriatric patients; use with caution in patients with renal or hepatic impairment
LenalidomideConstipation, cough, cytopenias, diarrhea, fatigue, nausea, peripheral edema, pyrexia, rash
Warnings: Hepatotoxicity, infusion-related reactions, myelosuppression, secondary malignancies, serious infections, TLS, tumor flare reactions, venous thromboembolism		Digoxin, erythropoiesis-stimulating agents, estrogen therapiesMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in geriatric patients and those with renal impairment
Liposomal doxorubicinAlopecia, anorexia, asthenia, back pain, cough, diarrhea, dyspepsia, dyspnea, hand-foot syndrome, headache, infection, mucositis, nausea, pharyngitis, pyrexia, rash, stomatitis, vomiting
Warnings: Cardiomyopathy, hand-foot syndrome, infusion-related reactions, secondary oral neoplasms		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients; reduce dose in patients with hepatic impairment
MethotrexateAbdominal distress, chills, dizziness, fatigue, infection, leukopenia, nausea, pyrexia, ulcerative stomatitis
Warnings: Gastrointestinal, renal, and neurologic toxicity; hypersensitivity; infertility; myelosuppression; pulmonary and hepatic toxicity; secondary malignancies; serious infections; skin reactions; TLS		Anticoagulants, antifolate drugs, aspirin, folic acid, hepatotoxic drugs, nephrotoxic products, nitrous oxide, NSAIDs, oral antibiotics (neomycin, penicillin, sulfonamide), probenecid, protein-bound drugs, proton pump inhibitors, sulfa drugs, weak acidsMay be harmful to fetus; avoid using in breastfeeding patients; monitor patients with renal or hepatic impairment  
MitoxantroneAbdominal pain, alopecia, bleeding, cardiovascular side effects, cough, diarrhea, dyspnea, headache, increased risk of infections, mucositis, nausea, pyrexia, sepsis, vomiting
Warnings: Congestive heart failure, hypersensitivity reaction, secondary leukemias, severe myelosuppression		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients
OxaliplatinCytopenias, diarrhea, elevated liver enzymes, emesis, fatigue, nausea, stomatitis
Warnings: Hemorrhage, hypersensitivity, peripheral sensory neuropathy, PRES, pulmonary and hepatic toxicity, rhabdomyolysis, severe myelosuppression		Anticoagulants, drugs that prolong QT interval, nephrotoxic drugsMay be harmful to fetus; avoid using in breastfeeding patients; reduce dosing in patients with renal impairment
PegaspargaseAbnormal blood clotting, elevated liver enzymes, febrile neutropenia, hyperglycemia, hypersensitivity, infections, pancreatitis, sepsis
Warnings: Anaphylaxis and serious hypersensitivity reactions, glucose intolerance, hemorrhage, hepatotoxicity, pancreatitis, thrombosis		GlucocorticoidsMay be harmful to fetus; avoid using in breastfeeding patients 
PentostatinAbdominal pain, anorexia, asthenia, chills, cough, cytopenias, diarrhea, dyspnea, fatigue, headache, myalgia, nausea, pyrexia, rhinitis, skin rash, stomatitis, upper respiratory infection, vomiting
Warnings: Acute pulmonary edema, hypotension, myelosuppression, neutropenia, rashes, renal toxicity		Allopurinol, vidarabine, fludarabine phosphate, carmustine, etoposide, high-dose cyclophosphamideMay be harmful to fetus; avoid using in breastfeeding patients
PralatrexateAnemia, constipation, cough, edema, epistaxis,  fatigue, nausea, mucositis, pyrexia, thrombocytopenia, vomiting
Warnings: Hepatotoxicity, mucositis, myelosuppression, skin reactions, TLS		Probenecid, NSAIDsMay be harmful to fetus; avoid using in breastfeeding patients 
VincristineAnemia, constipation, decreased appetite, diarrhea, fatigue, febrile neutropenia, insomnia, nausea, peripheral neuropathy, pyrexia
Warnings: Extravasation tissue injury, hepatic toxicity, myelosuppression, neurotoxicity, severe constipation and bowel obstruction, TLS		P-gp inhibitors or inducers, strong CYP3A inhibitors or inducersMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in patients with hepatic impairment
VinorelbineAsthenia, constipation, cytopenias, elevated liver enzymes, injection site reaction, nausea, peripheral neuropathy, vomiting
Warnings: Extravasation and tissue injury, hepatotoxicity, myelosuppression, neurotoxicity, pulmonary toxicity and renal failure, severe constipation and bowel obstruction		CYP3A inhibitorsMay be harmful to fetus; avoid using in breastfeeding patients; use with caution in patients with hepatic impairment

ACE = angiotensin-converting enzyme; CNS = central nervous system; G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; NSAIDs = nonsteroidal anti-inflammatory drugs; P-gp = P-glycoprotein; PML = progressive multifocal leukoencephalopathy; PRES = posterior reversible encephalopathy syndrome; TLS = tumor lysis syndrome.

From FDA-approved prescribing information.24-43

Monoclonal antibody agents interact with various parts of the immune system to block lymphoma cell growth or activate the patient’s immune system against cancer. Because of this interaction, monoclonal antibodies may trigger a severe immune-related reaction or hypersensitivity reaction. 

Patients undergoing treatment with monoclonal antibodies should be closely monitored for: 

  • Stevens-Johnson syndrome;
  • Toxic epidermal necrolysis;
  • Sudden fever, chills, nausea, vomiting, or tachycardia;
  • Signs of serious infections; and 
  • Autoimmune complications affecting the heart, liver, lungs, and kidneys. 

Patients may be treated with prophylactic acetaminophen and diphenhydramine before infusions to limit reactions. 

It is important to note that alemtuzumab is no longer commercially available in the United States due to the increased risk of infusion-related reactions, autoimmunity, stroke, and malignancies. Patients should be monitored for 2 hours after infusion for any signs of an adverse reaction. Serious and fatal infections with cytomegalovirus, Epstein-Barr virus, and Pneumocystis jirovecii have been reported following treatment. Patients undergoing treatment with monoclonal antibodies should be monitored for any signs of infection. 

Table 4. Side Effect Profiles of Monoclonal Antibody Agents

DrugMost Common Adverse EventsDrug-Drug InteractionsSpecial Population Considerations
Alemtuzumab
Note: This medication is no longer available commercially; however, it can be obtained through a restricted program for clinical use		Abdominal pain, anxiety, chills, CMV infection and viremia, cytopenias, dyspnea, emesis, insomnia, nausea, pyrexia, rash, tachycardia, urticaria
Warnings: Infusion-related reactions, immunosuppression and increased risk of infection, cytopenias		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients
Brentuximab vedotinDiarrhea, fatigue, nausea, neutropenia, peripheral neuropathy, pyrexia, upper respiratory infection
Warnings: Anaphylaxis, gastrointestinal complications, hematologic toxicities, hepatotoxicity, hyperglycemia, increased risk of infection, peripheral neuropathy, infusion-related reactions, PML, pulmonary toxicity, serious dermatologic reactions, TLS		Contraindicated for use with bleomycin due to pulmonary toxicity; P-gp inhibitors; strong CYP3A4 inducers or inhibitorsMay be harmful to fetus; avoid using in breastfeeding patients; not recommended in patients with moderate to severe hepatic impairment or severe renal impairment 
Mogamulizumab-kpkcAnemia, constipation, cough, diarrhea, edema, fatigue, headache, hypertension, infusion related-reactions, mucositis, musculoskeletal pain, nausea, pyrexia, skin infection, skin rash, thrombocytopenia, upper respiratory infection
Warnings: Autoimmune complications, complications of allogeneic HSCT after treatment, dermatologic toxicity, infection, infusion reactions		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients
NivolumabAbdominal pain, arthralgia, constipation, cough, diarrhea, dyspnea, fatigue, headache, hypothyroidism, infusion-related reactions, musculoskeletal pain, nasal congestion, nausea, peripheral neuropathy, pneumonia, pruritus, pyrexia, rash, upper respiratory infection, vomiting
Warnings: Complications of allogeneic HSCT, infusion-related reactions, severe and fatal immune-mediated adverse reactions		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients
PembrolizumabAbdominal pain, cough, diarrhea, dyspnea, fatigue, headache, hypothyroidism, musculoskeletal pain, nausea, peripheral neuropathy, pneumonitis, pruritus, pyrexia, rash, upper respiratory infection, urinary tract infection, vomiting
Warnings: Infusion-related reactions, severe and fatal immune-mediated adverse reactions		None indicatedMay be harmful to fetus; avoid using in breastfeeding patients

CMV = cytomegalovirus; HSCT = hematopoietic stem cell transplant; P-gp = P-glycoprotein; PML = progressive multifocal leukoencephalopathy; TLS = tumor lysis syndrome.

From FDA-approved prescribing information.44-48

Zidovudine is a nucleoside transcriptase inhibitor often prescribed to treat HIV-1 infection. Most safety studies and reports of side effects come from HIV-positive patients. Still, it is imperative to monitor patients for any adverse events and treat them as they arise. 

Table 5. Side Effect Profiles of Targeted Therapy

DrugMost Common Adverse EventsDrug-Drug InteractionsSpecial Population Considerations
ZidovudineAnorexia, asthenia, constipation, headache, malaise, nausea, vomiting
Warnings: Hematologic toxicity, lactic acidosis and severe hepatomegaly with steatosis, symptomatic myopathy		Doxorubicin, ribavirin, stavudineMonitor patients with hepatic impairment; dose selection in elderly patients should take reduced organ function and concomitant drug use into consideration

From FDA-approved prescribing information.49

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Author Bio

Emily Wagner earned a bachelor of science degree in biotechnology from the Rochester Institute of Technology in 2018 and a master of science degree in biomedical sciences with a focus in pharmacology from the University of Colorado Anschutz Medical Campus in 2020. During her thesis work, she studied non-small cell lung cancer and how the immune system plays a role in response to different treatments. Emily currently lives in Colorado where she enjoys the mountains, spending time with her dog, baking, and reading a good book.

Topics:

DDI Lymphoma Treatment Regimens