Multiple myeloma is a malignancy of the plasma cells. Multiple myeloma develops when clonal plasma cells proliferate in the bone marrow or form extramedullary plasmacytomas. The malignant plasma cells produce high levels of monoclonal protein, generally immunoglobulin G (IgG), IgM, IgA, or, very rarely, IgD. Multiple myeloma is associated with typical signs of end organ damage — hypercalcemia, renal insufficiency, anemia, and bone lesions — which are collectively known as CRAB symptoms.1,2
Multiple myeloma is generally preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SM). MGUS is an asymptomatic condition characterized by low levels of serum monoclonal protein and fewer than 10% clonal plasma cells in the bone marrow. SM occurs when serum monoclonal protein levels increase to greater than 3 gm/dL, urine monoclonal protein levels increase to greater than 500 mg per 24 hours, or the bone marrow contains 10% to 60% clonal plasma cells. Approximately 1% of MGUS cases and 10% of SM cases per year progress to multiple myeloma, but it is not clear which factors determine whether a clonal plasma cell will become malignant.1–3
In 2023, an expected 35,730 people will develop multiple myeloma in the United States, reflecting an increase of more than 40% since 1990.4 This cancer is uncommon, making up approximately 1.8% of all cancer diagnoses and 10% of all hematologic malignancies in the United States. Multiple myeloma is slightly more likely to affect men than women, and it is most prevalent in non-Hispanic Black populations. It typically affects older adults, and the median age at diagnosis is 69.1,2,4
Multiple myeloma mortality rates have decreased by 18% since 1994 due to the development of new therapies and treatment regimens. Multiple myeloma is responsible for 2.1% of US cancer deaths.4 For the 4% of individuals who are diagnosed with localized disease, in which a solitary plasmacytoma is identified, the 5-year relative survival rate is 79.5%. The remaining 96% of patients have systemic multiple myeloma, which comes with a 5-year relative survival rate of 59%.1,4
Multiple Myeloma Treatment
Multiple myeloma treatment options include multiple drug types, such as1,5:
- The first-in-class proteasome inhibitor bortezomib
- The next-generation proteasome inhibitors carfilzomib and ixazomib, which induce fewer off-target effects and adverse events like peripheral neuropathy
- Immunomodulatory drugs (IMiD) such as lenalidomide, pomalidomide, and thalidomide
- The steroid drug dexamethasone
- Anti-CD38 monoclonal antibodies, including daratumumab and isatuximab
- Other monoclonal antibodies such as elotuzumab, which targets the SLAMF7 receptor
- The chimeric antigen receptor (CAR) T-cell therapies idecabtagene vicleucel (also called ide-cel) and ciltacabtagene autoleucel (also called cilta-cel), which target B-cell maturation antigen (BCMA)
- The bispecific T-cell engager (BiTE) teclistamab-cqyv
When choosing treatment for a patient with multiple myeloma, clinicians should consider the patient’s risk level, comorbidities such as renal disease or neuropathy, and whether the patient is a candidate for hematopoietic stem cell transplantation (HSCT).1
Patient risk level is often assessed using the Revised International Staging System (R-ISS). This system stratifies patients with multiple myeloma into the following stages6:
- Stage I: Serum ꞵ-2 microglobulin <3.5 mg/L, serum albumin ≥3.5 g/dL, serum lactate dehydrogenase (LDH) greater than or equal to the upper limit of normal, and standard-risk chromosomal abnormalities
- Stage II: Not R-ISS stage I or II
- Stage III: Serum ꞵ-2 microglobulin ≥5.5 mg/L and either serum LDH greater than the upper limit of normal or high-risk chromosomal abnormalities
High-risk chromosomal abnormalities include del(17p), translocation t(4;14), and translocation t(14;16). These abnormalities should be detected using fluorescence in situ hybridization (FISH).6
Other factors that may indicate more aggressive or high-risk disease include6:
- Other cytogenetic abnormalities, including monosomy 17p, 1q21 gain or amplification, trisomies, MYC translocation, TP53 mutations, or complex karyotype
- High-risk gene expression signature
- A high degree of plasma cell proliferation
- Circulating plasma cells
- High serum free light chain (FLC)
- Renal failure
- Extramedullary disease
Management of Multiple Myeloma in Transplant-Eligible Patients
Autologous hematopoietic stem cell transplant (HSCT) should be considered for all eligible patients. In general, a patient who undergoes HSCT should have sufficient cardiac, pulmonary, hepatic, and renal function.1,6
Patients generally receive induction therapy before undergoing HSCT. For standard-risk patients, standard of care consists of 4 cycles of the triplet regimen VRd, which includes1,2,6:
Alternate induction therapy regimens may be considered if lenalidomide is not an option due to renal failure, increased risk for thromboembolism, or other factors that may lead to a higher likelihood of complications. Clinicians may consider VTd (bortezomib, thalidomide, and dexamethasone) or VCd, also called CyBorD (bortezomib, cyclophosphamide, and dexamethasone). Low-dose dexamethasone leads to fewer adverse events and may improve survival.2
Younger patients or those who are not candidates for bortezomib may also be able to use additional treatment regimens, including VRd plus daratumumab, KRd (carfilzomib, lenalidomide, and dexamethasone), or DRd (daratumumab, lenalidomide, and dexamethasone). However, it is not yet clear whether these treatment options lead to improved outcomes compared with VRd.2
Two-drug regimens may also be considered for patients who have a low performance status or are frail based on fitness levels measured by a tool such as the International Myeloma Working Group’s frailty score calculator. This tool takes into account age, comorbidities, and ability to carry out activities of daily living. If a patient’s performance status improves over the course of treatment, an additional drug may be added to the regimen.6
Patients with high-risk disease should receive VRd plus daratumumab or KRd. KRd leads to higher rates of complete response (CR) and minimal residual disease (MRD) negativity for patients with high-risk features.1,7
Following initial cycles of induction therapy, stem cells are harvested. The cells can be transplanted immediately. Alternatively, the cells can be stored and used for a future autologous HSCT following a first relapse or after the patient’s performance status improves.1,2,6
Some small studies as well as clinical observations have indicated that immunotherapies like pembrolizumab may be useful when implemented quickly after HSCT. Preliminary trials analyzing combination therapy with ipilimumab and nivolumab have also reported improved outcomes for patients with high-risk or relapsed myeloma. However, some clinical trials have not found the checkpoint inhibitors nivolumab and pembrolizumab to be effective, and multiple trials combining immunotherapies with IMiDs have been discontinued after they resulted in increased mortality.8,9 Ultimately, the combination of pembrolizumab, an IMiD, and dexamethasone should not be used outside of a clinical trial.10
Induction therapy is typically followed by maintenance therapy with lenalidomide for standard-risk patients and a proteasome inhibitor such as bortezomib for high-risk patients.1,2
Multiple Myeloma Treatment in Transplant-Ineligible Patients
If HSCT is not an option, patients typically receive VRd, DRd, VCd, or VTd induction therapy for 8 to 12 cycles. Other recommended treatment options include KRd, VCd pus daratumumab, or a combination of daratumumab, bortezomib, melphalan, and prednisone.1,2,6
Research indicates that lenalidomide likely does not improve prognosis for patients with high-risk multiple myeloma. Patients in this category should seek out clinical trials, when available.6,7
Maintenance therapy consists of lenalidomide, with or without dexamethasone. Patients can also receive maintenance bortezomib or ixazomib. Frail patients may be treated with lenalidomide and dexamethasone until disease progression occurs.1,2
Managing Extramedullary Disease
In up to 5% of cases, multiple myeloma may spread to the lymph nodes, abdominal organs, skin, or upper airway. Because of the rarity of this condition, clinical data describing effective treatments for extramedullary disease are very limited.11
Very rarely, extramedullary disease may occur in the central nervous system (CNS) at diagnosis or during relapse. Most systemic therapies cannot effectively eradicate myeloma cells or are not generally capable of crossing the blood-brain barrier. However, limited data indicate that bendamustine and marizomib may be effective at treating CNS disease when combined with radiation therapy, thalidomide, and dexamethasone. HSCT, cranial radiation, or intrathecal hydrocortisone, methotrexate, and/or cytarabine may also be options for treating CNS disease.11
Treatment for Relapsed and Refractory Multiple Myeloma
Treatment decisions for relapsed myeloma are based on relapse timing, response to previous treatments, the degree of relapse aggressiveness, and patient performance status. In particular, a patient is considered to have high-risk relapsed disease if the relapse occurs within 1 year of induction therapy.1,2
Relapsed multiple myeloma may be treated with various triplet regimens, including2,6,8:
- VCd, with or without daratumumab
- Daratumumab, bortezomib, and dexamethasone
- Daratumumab, pomalidomide, and dexamethasone
- Carfilzomib, pomalidomide, and dexamethasone
- Carfilzomib, cyclophosphamide, and dexamethasone
- Ixazomib, lenalidomide, and dexamethasone
- Ixazomib, cyclophosphamide, and dexamethasone
- Elotuzumab, lenalidomide, and dexamethasone
- Elotuzumab, bortezomib, and dexamethasone
- Bendamustine, lenalidomide, and dexamethasone
- Bendamustine, bortezomib, and dexamethasone
- Liposomal doxorubicin, bortezomib, and dexamethasone
- Selinexor, bortezomib, and dexamethasone
The National Comprehensive Cancer Network (NCCN) recommends VRd and IRd as the preferred treatment regimens for patients with multiple myeloma following a relapse.6 The International Myeloma Working Group (IMWG) prefers DRd and KRd for patients with disease that is not refractory to lenalidomide.12
If relapse occurs more than 6 months after initial therapy, the induction therapy regimen can be used. Other treatment options for patients who experience a late relapse and have tried 3 prior therapies include high-dose or fractionated cyclophosphamide, or bendamustine as a single agent or in combination with dexamethasone and an IMiD or proteasome inhibitor.6
Patients with the t(11;14) translocation can also be treated with venetoclax, a BCL-2 inhibitor. Regimens containing anthracyclines may be considered when relapses are aggressive.2
The NCCN’s recommended treatment options for refractory multiple myeloma are described in Table 1.
Table 1. NCCN Recommended Regimens for Refractory Multiple Myeloma6
|New Refractory Disease||Refractory Disease Previously Treated With 1 Line of Therapy||Refractory Disease Previously Treated With 2 Lines of Therapy||Refractory Disease Previously Treated With 2 Lines of Therapy and With Disease Progression Within 61 Days of Initial Therapy|
|Bortezomib- refractory disease||DRd; KRd; a combination of daratumumab, carfilzomib, and dexamethasone; a combination of carfilzomib, pomalidomide, and dexamethasone; or a combination of isatuximab, carfilzomib, and dexamethasone||Daratumumab, pomalidomide, and dexamethasone||Isatuximab, pomalidomide, and dexamethasone||Ixazomib, pomalidomide, and dexamethasone|
|Lenalidomide- refractory disease||DVd; a combination of daratumumab, carfilzomib, and dexamethasone; a combination of carfilzomib, pomalidomide, and dexamethasone; or a combination of isatuximab, carfilzomib, and dexamethasone||Daratumumab, pomalidomide, and dexamethasone||Isatuximab, pomalidomide, and dexamethasone||A combination of pomalidomide, bortezomib, and dexamethasone; or a combination of Ixazomib, pomalidomide, and dexamethasone|
From the NCCN.6
A first or additional HSCT may also be considered during relapse or progression of multiple myeloma if the patient is a candidate. Either an autologous or allogeneic transplant may be considered.6
The US Food and Drug Administration (FDA) recently approved teclistamab-cqyv for the treatment of relapsed or refractory multiple myeloma. Teclistamab-cqyv is a BiTE that targets both CD3 on T cells and BCMA on B cells. It can be used by patients with multiple myeloma who have previously received 4 other therapies, including a proteasome inhibitor, an IMiD, and an anti-CD38 monoclonal antibody. Additional BiTEs are also being tested in clinical trials as single agents or in combination with an IMiD.8,13
Another option for patients with relapsed or refractory multiple myeloma who have received 4 or more lines of therapy is CAR T-cell therapy. Idecabtagene vicleucel and ciltacabtagene autoleucel tend to provide effective early responses, but these responses are not typically durable. Early studies show that CAR T-cell therapy may produce improved results when given early after HSCT or when paired with agents like IMiDs, monoclonal antibodies, or γ-secretase inhibitors; however, research is ongoing.8,14,15
Nearly all patients will eventually experience relapse or disease progression, regardless of initial risk stratification or treatment plan. Eventually, patients may face a lack of treatment options and begin or continue palliative care or hospice.6
When and How To Use Approved Pharmacotherapies for Multiple Myeloma
The administration and dosage information for various multiple myeloma medications are summarized in Tables 2-4.
Table 2. Management Guidelines for Chemotherapy for Multiple Myeloma
|Drug||Administration||Dose||Frequency of Administration|
|Bendamustine||IV infusion||Multiple doses can be used; see prescribing information for more details||Multiple cycles and schedules can be used; see prescribing information for more details|
|Cyclophosphamide||IV infusion||40-50 mg/kg for patients with no hematologic deficiency; alternatively, 10-15 mg/kg or 3-5 mg/kg||Divided doses over 2-5 d if giving 40-50 mg/kg dose; every 7-10 d if giving 10-15 mg/kg dose; twice per wk if giving 3-5 mg/kg dose|
IV = intravenous.
From FDA-approved prescribing information.16,17
Table 3. Management Guidelines for ImiDs for Multiple Myeloma
|Drug||Administration||Dose||Frequency of Administration|
|Lenalidomide||Oral capsule||25 mg||Once daily on days 1 to 21 of each 28-d cycle|
|Pomalidomide||Oral capsule||4 mg||Once daily on days 1 to 21 of each 28-d cycle|
|Thalidomide||Oral capsule||200 mg||Once daily|
From FDA-approved prescribing information.18–20
Table 4. Management Guidelines for Monoclonal Antibodies and Immunotherapy for Multiple Myeloma
|Drug||Administration||Dose||Frequency of Administration|
|Bortezomib||SC or IV injection; SC is preferred6||1.3 mg/m2||Once or twice per wk; once per wk is preferred6|
|Carfilzomib||IV injection given over 2-10 min||20 mg/m2/d for cycle 1 dose; increase to 27 mg/m2/d if tolerated||2 consecutive days each wk for three wk, followed by a 12-d rest|
|Ciltacabtagene autoleucel||Suspension for IV infusion||0.5-1 x 106 CAR-positive T cells/kg||Single administration|
|Daratumumab||May consist of IV infusion of daratumumab or SC injection of daratumumab and hyaluronidase-fihj6||16 mg/kg for an IV infusion||Various schedules are used; see prescribing information for details|
|Elotuzumab||IV infusion||10 mg/kg when administered with lenalidomide and dexamethasone; 10 mg/kg for the first 2 cycles and 20 mg/kg for subsequent cycles when administered with pomalidomide and dexamethasone||Once per wk for the first 2 cycles and once every 2 wk after when administered with lenalidomide and dexamethasone; once per wk for the first 2 cycles and once every 4 wk after when administered with pomalidomide and dexamethasone|
|Idecabtagene vicleucel||Suspension for IV infusion||300-400 x 106 CAR-positive T cells||Single administration|
|Isatuximab||IV infusion||10 mg/kg||Once per wk for the first 4 weeks and then once every 2 wk|
|Ixazomib||Oral capsule||4 mg||Days 1, 8, and 15 of a 28-d cycle|
|Marizomib||IV infusion given over 1 h||10 mg/kg||Once every 2 wk|
|Panobinostat||Oral capsule||20 mg||Days 1, 3, 5, 8, 10, and 12 of a 21-d cycle for 8 cycles|
|Teclistamab-cqyv||SC injection||Dosages are ramped; see prescribing information for details||Days 1, 4, and 7 for step-up dosing, followed by weekly injections starting 1 week after day 7|
|Venetoclax||Oral tablet||Dosages are ramped; see prescribing information for details||Daily|
CAR = chimeric antigen receptor; IV = intravenous; SC = subcutaneous.
From FDA-approved prescribing information.21–32
Monitoring Adverse Events and Drug-Drug Interactions for Multiple Myeloma Treatments
Adverse event monitoring of patients with multiple myeloma is imperative.
Supportive treatments may help prevent or manage these events. For multiple myeloma, supportive care may include1,6:
- Antithrombotic treatments such as aspirin, low-molecular-weight heparin, rivaroxaban, apixaban, fondaparinux, or warfarin
- Bisphosphonates or bone-stimulating agents for the prophylaxis or treatment of bone lesions and fractures
- Acyclovir treatments while receiving bortezomib to prevent viral infections
- Hydration or treatments for hypercalcemia, hyperuricemia, or other abnormalities for those experiencing renal toxicity
Treatment regimens can also be modified in the case of renal toxicity. Lower doses of lenalidomide and dexamethasone may be suitable for this patient population. If renal function improves, patients can switch to another treatment regimen.1,6
The following tables include information about common adverse events, drug-drug interactions, and considerations for use in special populations for multiple myeloma drugs.
Table 5. Side Effect Profiles for Chemotherapy for Multiple Myeloma
|Drug||Most Common Adverse Events||Side Effects That May Necessitate Treatment Discontinuation or Modification||Drug-Drug Interactions||Use in Special Populations|
|Bendamustine||Fever, fatigue, nausea, vomiting, diarrhea, constipation, anorexia, weight loss, cough, headache, shortness of breath, rash, stomatitis (oral mucositis), lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia||Myelosuppression, severe skin reactions||Inducers and inhibitors of CYP1A2||Contraindicated in pregnant or lactating individuals|
|Cyclophosphamide||Neutropenia, fever, alopecia, nausea, vomiting, diarrhea||Severe hemorrhagic cystitis||Protease inhibitors, ACE inhibitors, natalizumab, paclitaxel, thiazide diuretics, zidovudine, anthracyclines, cytarabine, pentostatin, trastuzumab, G-CSF, GM-CSF, amphotericin B, indomethacin, azathioprine, busulfan, etanercept, metronidazole, tamoxifen, coumarins, cyclosporine, depolarizing muscle relaxants||Contraindicated in those with urinary outflow obstruction and in pregnant or lactating individuals|
ACE = angiotensin-converting enzyme; G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor
From FDA-approved prescribing information.16,17
Table 6. Side Effect Profiles for ImiDs for Multiple Myeloma
|Drug||Most Common Adverse Events||Side Effects That May Necessitate Treatment Discontinuation or Modification||Drug-Drug Interactions||Use in Special Populations|
|Lenalidomide||Fatigue, neutropenia, nausea, constipation, diarrhea, muscle cramps, back pain, fever, peripheral edema, upper respiratory tract infection, shortness of breath, dizziness, tremor, rash, anemia, thrombocytopenia||Allergic reaction, hematologic toxicity, hepatotoxicity||Digoxin, erythropoietin-stimulating agents, estrogen therapies||Contraindicated in pregnant individuals|
|Pomalidomide||Fatigue, asthenia, nausea, diarrhea, constipation, shortness of breath, upper respiratory tract infection, back pain, fever, anemia, neutropenia||Hematologic toxicity||None indicated||Contraindicated in pregnant individuals|
|Thalidomide||Fatigue, asthenia, dizziness, shortness of breath, edema, muscle weakness, constipation, nausea, neuropathy, rash, dry skin, tremor, fever, anorexia, weight loss, weight gain, confusion, anxiety, hypocalcemia, leukopenia, neutropenia, thrombosis||Neutropenia, bradycardia, peripheral neuropathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, severe drowsiness||Opioids, antihistamines, antipsychotics, anti-anxiety agents, CNS depressants, drugs that cause bradycardia or peripheral neuropathy||Contraindicated in pregnant individuals|
CNS = central nervous system
From FDA-approved prescribing information.18-20
Table 7. Side Effect Profiles for Monoclonal Antibodies and Immunotherapy for Multiple Myeloma
|Drug||Most Common Adverse Events||Side Effects that May Require Treatment Discontinuation or Modification||Drug-Drug Interactions||Use in Special Populations|
|Bortezomib||Nausea, vomiting, diarrhea, constipation, fatigue, peripheral neuropathy, neuralgia, rash, fever, anorexia, thrombocytopenia, neutropenia, anemia, leukopenia, lymphopenia||Peripheral neuropathy, pulmonary toxicity, posterior reversible encephalopathy syndrome, severe gastrointestinal toxicity, hepatic toxicity||Strong inducers or inhibitors of CYP3A5||Contraindicated in pregnant and lactating individuals and in individuals with hypersensitivity to boron or mannitol|
|Carfilzomib||Fatigue, nausea, diarrhea, shortness of breath, fever, anemia, thrombocytopenia||Cardiac adverse reactions (including ischemia and heart failure), pulmonary complications (including pulmonary hypertension), hepatic toxicity, thrombocytopenia, tumor lysis syndrome||None indicated||If the patient is on dialysis, use carfilzomib after dialysis; contraindicated in pregnant and lactating individuals|
|Ciltacabtagene autoleucel||CRS, fever, chills, fatigue, dizziness, infection, musculoskeletal pain, cough, shortness of breath, upper respiratory tract infection, nausea, vomiting, diarrhea, constipation, anorexia, headache, edema, encephalopathy, coagulopathy, hypogammaglobulinemia, hypotension, tachycardia, thrombocytopenia, neutropenia, anemia, aminotransferase elevation, hypoalbuminemia||N/A||Contraindicated in pregnant and lactating individuals|
|Daratumumab||Infusion reactions, fatigue, nausea, diarrhea, muscle spasms, back pain, shortness of breath, cough, upper respiratory tract infection, fever, edema, peripheral neuropathy, neutropenia, thrombocytopenia||Infusion reactions, neutropenia, thrombocytopenia||Interferes with indirect antiglobulin test (Coombs test) and serum protein electrophoresis||None indicated|
|Elotuzumab||Fatigue, diarrhea, constipation, fever, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, anorexia, pneumonia, hyperglycemia||Grade 2 or higher infusion reactions, hepatotoxicity||Interferes with serum protein electrophoresis||None indicated|
|Idecabtagene vicleucel||CRS, infection, fatigue, musculoskeletal pain, nausea, diarrhea, cough, upper respiratory tract infection, encephalopathy, edema, anorexia, fever, headache, hypogammaglobulinemia, neutropenia, leukopenia, lymphopenia, thrombocytopenia, anemia||N/A||None indicated||Contraindicated in pregnant and lactating individuals|
|Isatuximab||Infusion reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, neutropenia, lymphopenia, thrombocytopenia||Infusion reactions, neutropenia||Interferes with indirect antiglobulin test (Coombs test) and serum protein electrophoresis||Contraindicated in pregnant and lactating individuals|
|Ixazomib||Diarrhea, constipation, nausea, vomiting, peripheral neuropathy, edema, back pain, thrombocytopenia||Thrombocytopenia, gastrointestinal toxicity, peripheral neuropathy, peripheral edema, cutaneous reactions||Strong inducers of CYP3A||Reduce starting dose in those with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease; contraindicated in pregnant and lactating individuals|
|Marizomib||Infusion reactions, headache, ARIA-edema||Infusion reactions, ARIA-hemosiderin deposition||None indicated||None indicated|
|Panobinostat||Fatigue, nausea, vomiting diarrhea, edema, anorexia, fever, hypophosphatemia, hypokalemia, hyponatremia, increased creatinine, thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia||Hepatotoxicity, cardiac toxicity, myelosuppression, moderate or severe diarrhea, infection||Strong inducers and inhibitors of CYP3A4, sensitive CYP2D6 substrates, anti-arrhythmic drugs/QT-prolonging drugs||Reduce dose in individuals with hepatic impairment; contraindicated in pregnant and lactating individuals|
|Teclistamab-cqyv||CRS, injection site reaction, fatigue, fever, headache, musculoskeletal pain, upper respiratory tract infection, pneumonia, nausea, diarrhea, lymphopenia, neutropenia, leukopenia, thrombocytopenia||Infection, hypersensitivity or other administration reactions, severe neurologic toxicity, hepatotoxicity, severe neutropenia||CYP substrates (particularly during initial step-up dosing)||Contraindicated in pregnant and lactating individuals|
|Venetoclax||Fatigue, nausea, vomiting, diarrhea, constipation, cough, shortness of breath, upper respiratory tract infection, pneumonia, musculoskeletal pain, back pain, abdominal pain, oropharyngeal pain, edema, fever, dizziness, hemorrhage, sepsis, rash, hypotension, neutropenia, anemia, thrombocytopenia||Severe neutropenia||Strong inducers and inhibitors of CYP3A, warfarin, P-gp substrates||Contraindicated in pregnant and lactating individuals|
ARIA = amyloid related imaging abnormalities; CYP = cytochrome P450; CRS = cytokine release syndrome; P-gp = P-glycoprotein.
From FDA-approved prescribing information.21-32
Monitoring Complications of Immune Therapies
Patients receiving treatment with CAR T-cell therapy or BiTEs should be monitored for cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), as these are potentially life-threatening complications that require immediate treatment.
CRS occurs when highly effective immune therapies trigger high levels of T-cell stimulation, an aggressive inflammatory response, and a cytokine storm. Potential signs of CRS include flu-like symptoms, fatigue, joint or muscle pain, nausea, vomiting, fever, rash, hypotension, tachycardia, arrhythmia, hypoxia, seizures, circulatory shock, and, eventually, multiorgan system failure.33
Clinicians should monitor for CRS by looking for elevated levels of C-reactive protein (CRP), creatinine, and liver enzymes as well as cytopenias and signs of coagulopathy. Some cases of CRS can be treated with increased fluids, antipyretic agents, and antihistamines. Severe CRS cases require tocilizumab or other anti-IL-6 monoclonal antibodies.33
TLS develops when multiple malignant cells are eliminated within a short amount of time. Symptoms of TLS include fatigue, nausea, vomiting, decreased appetite, numbness, arrhythmia, dark urine, decreased urine output, and seizures.34
Clinicians should monitor for TLS by evaluating for decreased levels of calcium or increased levels of uric acid, potassium, and phosphorus. TLS treatments include intravenous hydration, diuretics, and rasburicase.35
Multiple Myeloma Treatment Guidelines
Numerous organizations have established guidelines for the management of patients with multiple myeloma.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Multiple Myeloma — Version 3.2023
- Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Collection of Treatment Guidelines for Multiple Myeloma
- Treatment of Multiple Myeloma With High-Risk Cytogenetics: A Consensus of the International Myeloma Working Group
- Treatment of Relapsed and Refractory Multiple Myeloma: Recommendations from the International Myeloma Working Group
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Maureen McNulty studied molecular genetics and English at Ohio State University. She has spent more than a decade researching the genetic causes of — and possible treatments for — multiple types of cancer. Maureen is now a medical writer who is passionate about helping people use science to enrich their lives.