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

Figure. Photomicrograph of hematoxylin and eosin stain reflecting multiple myeloma.  Credit: Getty Images.
Figure. Photomicrograph of hematoxylin and eosin stain reflecting multiple myeloma. Credit: Getty Images.

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

Risk Stratification

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
  • Thrombocytopenia
  • Lymphopenia
  • Immunoparesis
  • Extramedullary disease
  • Frailty

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

  • Bortezomib
  • Lenalidomide
  • Dexamethasone

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:

  • VRd
  • VCd, with or without daratumumab
  • VTd
  • KRd
  • DRd
  • 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 DiseaseRefractory Disease Previously Treated With 1 Line of TherapyRefractory Disease Previously Treated With 2 Lines of TherapyRefractory Disease Previously Treated With 2 Lines of Therapy and With Disease Progression Within 61 Days of Initial Therapy
Bortezomib- refractory diseaseDRd; KRd; a combination of daratumumab, carfilzomib, and dexamethasone; a combination of carfilzomib, pomalidomide, and dexamethasone; or a combination of isatuximab, carfilzomib, and dexamethasoneDaratumumab, pomalidomide, and dexamethasoneIsatuximab, pomalidomide, and dexamethasoneIxazomib, pomalidomide, and dexamethasone
Lenalidomide- refractory diseaseDVd; a combination of daratumumab, carfilzomib, and dexamethasone; a combination of carfilzomib, pomalidomide, and dexamethasone; or a combination of isatuximab, carfilzomib, and dexamethasoneDaratumumab, pomalidomide, and dexamethasoneIsatuximab, pomalidomide, and dexamethasoneA 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

DrugAdministrationDoseFrequency of Administration
BendamustineIV infusionMultiple doses can be used; see prescribing information for more detailsMultiple cycles and schedules can be used; see prescribing information for more details
CyclophosphamideIV infusion40-50 mg/kg for patients with no hematologic deficiency; alternatively, 10-15 mg/kg or 3-5 mg/kgDivided 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

DrugAdministrationDoseFrequency of Administration
LenalidomideOral capsule25 mgOnce daily on days 1 to 21 of each 28-d cycle
PomalidomideOral capsule4 mgOnce daily on days 1 to 21 of each 28-d cycle
ThalidomideOral capsule200 mgOnce daily

From FDA-approved prescribing information.18–20

Table 4. Management Guidelines for Monoclonal Antibodies and Immunotherapy for Multiple Myeloma

DrugAdministrationDoseFrequency of Administration
BortezomibSC or IV injection; SC is preferred61.3 mg/m2 Once or twice per wk; once per wk is preferred6
CarfilzomibIV injection given over 2-10 min20 mg/m2/d for cycle 1 dose; increase to 27 mg/m2/d if tolerated2 consecutive days each wk for three wk, followed by a 12-d rest 
Ciltacabtagene autoleucelSuspension for IV infusion0.5-1 x 106 CAR-positive T cells/kgSingle administration
DaratumumabMay consist of IV infusion of daratumumab or SC injection of daratumumab and hyaluronidase-fihj616 mg/kg for an IV infusionVarious schedules are used; see prescribing information for details
ElotuzumabIV infusion10 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 dexamethasoneOnce 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 vicleucelSuspension for IV infusion300-400 x 106 CAR-positive T cellsSingle administration
IsatuximabIV infusion10 mg/kgOnce per wk for the first 4 weeks and then once every 2 wk
IxazomibOral capsule4 mgDays 1, 8, and 15 of a 28-d cycle
MarizomibIV infusion given over 1 h10 mg/kgOnce every 2 wk
PanobinostatOral capsule20 mgDays 1, 3, 5, 8, 10, and 12 of a 21-d cycle for 8 cycles
Teclistamab-cqyvSC injectionDosages are ramped; see prescribing information for detailsDays 1, 4, and 7 for step-up dosing, followed by weekly injections starting 1 week after day 7
VenetoclaxOral tabletDosages are ramped; see prescribing information for detailsDaily

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

DrugMost Common Adverse EventsSide Effects That May Necessitate Treatment Discontinuation or ModificationDrug-Drug InteractionsUse in Special Populations
BendamustineFever, fatigue, nausea, vomiting, diarrhea, constipation, anorexia, weight loss, cough, headache, shortness of breath, rash, stomatitis (oral mucositis), lymphopenia, anemia, leukopenia, thrombocytopenia, neutropeniaMyelosuppression, severe skin reactionsInducers and inhibitors of CYP1A2Contraindicated in pregnant or lactating individuals
CyclophosphamideNeutropenia, fever, alopecia, nausea, vomiting, diarrheaSevere 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 relaxantsContraindicated 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

DrugMost Common Adverse EventsSide Effects That May Necessitate Treatment Discontinuation or ModificationDrug-Drug InteractionsUse in Special Populations
LenalidomideFatigue, neutropenia, nausea, constipation, diarrhea, muscle cramps, back pain, fever, peripheral edema, upper respiratory tract infection, shortness of breath, dizziness, tremor, rash, anemia, thrombocytopeniaAllergic reaction, hematologic toxicity, hepatotoxicityDigoxin, erythropoietin-stimulating agents, estrogen therapiesContraindicated in pregnant individuals
PomalidomideFatigue, asthenia, nausea, diarrhea, constipation, shortness of breath, upper respiratory tract infection, back pain, fever, anemia, neutropeniaHematologic toxicityNone indicatedContraindicated in pregnant individuals
ThalidomideFatigue, 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, thrombosisNeutropenia, bradycardia, peripheral neuropathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, severe drowsinessOpioids, antihistamines, antipsychotics, anti-anxiety agents, CNS depressants, drugs that cause bradycardia or peripheral neuropathyContraindicated 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

DrugMost Common Adverse EventsSide Effects that May Require Treatment Discontinuation or ModificationDrug-Drug InteractionsUse in Special Populations
BortezomibNausea, vomiting, diarrhea, constipation, fatigue, peripheral neuropathy, neuralgia, rash, fever, anorexia, thrombocytopenia, neutropenia, anemia, leukopenia, lymphopeniaPeripheral neuropathy, pulmonary toxicity, posterior reversible encephalopathy syndrome, severe gastrointestinal toxicity, hepatic toxicityStrong inducers or inhibitors of CYP3A5Contraindicated in pregnant and lactating individuals and in individuals with hypersensitivity to boron or mannitol
CarfilzomibFatigue, nausea, diarrhea, shortness of breath, fever, anemia, thrombocytopeniaCardiac adverse reactions (including ischemia and heart failure), pulmonary complications (including pulmonary hypertension), hepatic toxicity, thrombocytopenia, tumor lysis syndromeNone indicatedIf the patient is on dialysis, use carfilzomib after dialysis; contraindicated in pregnant and lactating individuals
Ciltacabtagene autoleucelCRS, 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, hypoalbuminemiaN/AContraindicated in pregnant and lactating individuals
DaratumumabInfusion reactions, fatigue, nausea, diarrhea, muscle spasms, back pain, shortness of breath, cough, upper respiratory tract infection, fever, edema, peripheral neuropathy, neutropenia, thrombocytopeniaInfusion reactions, neutropenia, thrombocytopeniaInterferes with indirect antiglobulin test  (Coombs test) and serum protein electrophoresisNone indicated
ElotuzumabFatigue, diarrhea, constipation, fever, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, anorexia, pneumonia, hyperglycemiaGrade 2 or higher infusion reactions, hepatotoxicityInterferes with serum protein electrophoresisNone indicated
Idecabtagene vicleucelCRS, infection, fatigue, musculoskeletal pain, nausea, diarrhea, cough, upper respiratory tract infection, encephalopathy, edema, anorexia, fever, headache, hypogammaglobulinemia, neutropenia, leukopenia, lymphopenia, thrombocytopenia, anemiaN/ANone indicatedContraindicated in pregnant and lactating individuals
IsatuximabInfusion reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, neutropenia, lymphopenia, thrombocytopeniaInfusion reactions, neutropeniaInterferes with indirect antiglobulin test (Coombs test) and serum protein electrophoresisContraindicated in pregnant and lactating individuals
IxazomibDiarrhea, constipation, nausea, vomiting, peripheral neuropathy, edema, back pain, thrombocytopenia Thrombocytopenia, gastrointestinal toxicity, peripheral neuropathy, peripheral edema, cutaneous reactionsStrong inducers of CYP3AReduce starting dose in those with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease; contraindicated in pregnant and lactating individuals
MarizomibInfusion reactions, headache, ARIA-edemaInfusion reactions, ARIA-hemosiderin depositionNone indicatedNone indicated
PanobinostatFatigue, nausea, vomiting diarrhea, edema, anorexia, fever, hypophosphatemia, hypokalemia, hyponatremia, increased creatinine, thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemiaHepatotoxicity, cardiac toxicity, myelosuppression, moderate or severe diarrhea, infectionStrong inducers and inhibitors of CYP3A4, sensitive CYP2D6 substrates, anti-arrhythmic drugs/QT-prolonging drugsReduce dose in individuals with hepatic impairment; contraindicated in pregnant and lactating individuals
Teclistamab-cqyvCRS, injection site reaction, fatigue, fever, headache, musculoskeletal pain, upper respiratory tract infection, pneumonia, nausea, diarrhea, lymphopenia, neutropenia, leukopenia, thrombocytopeniaInfection, hypersensitivity or other administration reactions, severe neurologic toxicity, hepatotoxicity, severe neutropeniaCYP substrates (particularly during initial step-up dosing)Contraindicated in pregnant and lactating individuals
VenetoclaxFatigue, 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 neutropeniaStrong inducers and inhibitors of CYP3A, warfarin, P-gp substratesContraindicated 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.


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10. Pembrolizumab [package insert]. Merck & Co., Inc.; 2021. Accessed May 19, 2023.  

11. Egan PA, Elder PT, Deighan WI, O’Connor SJM, Alexander HD. Multiple myeloma with central nervous system relapse. Haematologica. 2020;105(7):1780-1790. doi:10.3324/haematol.2020.248518 

12. Moreau P, Kumar SK, San Miguel J, et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e105-e118. doi:10.1016/S1470-2045(20)30756-7 

13. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. US Food and Drug Administration. Published online October 25, 2022. Accessed May 11, 2023. 

14. Jaber N. Carvykti approval marks second CAR T-cell therapy for multiple myeloma. National Cancer Institute. Published March 30, 2022. Accessed May 11, 2023. 

15. Jaber N. FDA approves BCMA-targeted CAR T-cell therapy for multiple myeloma.  National Cancer Institute. Published April 14, 2021. Accessed May 11, 2023. 

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27. Leqembi [package insert]. Esai Inc.; 2023. Accessed May 22, 2023.  

28. Farydak [package insert]. Novartis Pharmaceuticals Corporation; 2015. Accessed May 22, 2023.

29. Venclexta [package insert]. AbbVie Inc.; 2018. Accessed May 22, 2023. 

30. Abecma [package insert]. Celgene Corporation; 2021. Accessed May 22, 2023.  

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32. Tecvayli [package insert]. Janssen Biotech, Inc.; 2022. Accessed May 19, 2023.  

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34. Gupta A, Moore JA. Tumor lysis syndrome. JAMA Oncol. 2018;4(6):895. doi:10.1001/jamaoncol.2018.0613 

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Author Bio

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.