Indication
XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.

A case discussion: Use of BTAs in the absence of bone pain

Watch two physicians discuss initiating a BTA for a patient with breast cancer and bone metastases who isn't experiencing bone pain.

See more videos like this

Expert insight: Watch two video discussions about the immediate and subsequent risk of bone complications in solid tumors and bone metastases

How do bone metastases from solid tumors lead to bone complications?

Watch to learn about the vicious cycle of bone destruction.

Now see how XGEVA® can help

Bone disease is an important diagnostic feature of multiple myeloma 10

Active multiple myeloma is defined as clonal bone marrow cells >10% or biopsy-proven bony or extramedullary plasmacytoma plus any one or more CRAB features or myeloma-defining event (MDE) biomarkers

  • CRAB
  • MDE biomarkers

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C

HyperCalcemia

Serum calcium >1 mg/dL above ULN or >11 mg/dL 10

19

of patients 11

R

Renal insufficiency

CrCl <40 mL/min or serum creatinine >2 mg/dL 10

40

of patients 12

A

Anemia

Hemoglobin >20 g/L below LLN or <100 g/L 10

39

of patients 11

B

Bone lesions

1 or more lesions on skeletal radiography, CT, or PET-CT 10, §

70

of patients 13,14

Bone lesions are the most prevalent CRAB feature present at diagnosis 13,14

Multiple myeloma directly harms the kidneys, potentially complicating bone-targeting treatment for patients with renal impairment. 12,14

§F-fluorodeoxyglucose PET with CT.

CrCl, creatinine clearance; CT, computed tomography; LLN, lower limit of normal; PET, positron emission tomography; ULN, upper limit of normal.

One or more MDE biomarkers is sufficient to make a diagnosis 10

These are defined as:

  • Bone marrow clonal plasmacytosis (≥60%)
  • Serum involved/uninvolved FLC ratio ≥100 (provided involved FLC is ≥100 mg/L)
  • >1 focal lesion on MRI

FLC, free light chain; MRI, magnetic resonance imaging.

9 out of 10

As many as 9 out of 10 patients

with multiple myeloma will develop lytic bone lesions, which often lead to bone complications 6,14

How do bone lesions in multiple myeloma lead to bone complications?

Watch how RANKL can lead to excessive bone resorption when overproduced by multiple myeloma cells. 15

Now see how XGEVA® can help

RANKL, RANK ligand.

Important Safety Information

Hypocalcemia

Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be closely monitored. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.

Hypersensitivity

XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.

Drug Products with Same Active Ingredient

Patients receiving XGEVA® should not take Prolia® (denosumab).

Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) has been reported in patients receiving XGEVA®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with cancer, the incidence of ONJ was higher with longer duration of exposure.

Patients with a history of tooth extraction, poor oral hygiene, or use of a dental appliance are at a greater risk to develop ONJ. Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections.

Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®. Consider temporarily interrupting XGEVA® therapy if an invasive dental procedure must be performed.

Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture

Atypical femoral fracture has been reported with XGEVA®. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.

Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone (GCTB) and in Patients with Growing Skeletons

Clinically significant hypercalcemia requiring hospitalization and complicated by acute renal injury has been reported in XGEVA®-treated patients with GCTB and in patients with growing skeletons within one year of treatment discontinuation. Monitor patients for signs and symptoms of hypercalcemia after treatment discontinuation and treat appropriately.

Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation

Multiple vertebral fractures (MVF) have been reported following discontinuation of treatment with denosumab. Patients at higher risk for MVF include those with risk factors for or a history of osteoporosis or prior fractures. When XGEVA® treatment is discontinued, evaluate the individual patient’s risk for vertebral fractures.

Embryo-Fetal Toxicity

XGEVA® can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA® is expected to result in adverse reproductive effects.

Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.

Adverse Reactions

The most common adverse reactions in patients receiving XGEVA® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.

For multiple myeloma patients receiving XGEVA®, the most common adverse reactions were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. The most common serious adverse reaction was pneumonia. The most common adverse reaction resulting in discontinuation of XGEVA® was osteonecrosis of the jaw.

Indication

XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.

Please see full Prescribing Information.

 

Important Safety Information

Hypocalcemia

Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be..

References:

  1. XGEVA® (denosumab) prescribing information, Amgen.
  2. Kuchuk I, Hutton B, Moretto P, et al. Incidence, consequences and treatment of bone metastases in breast cancer patients—experience from a single cancer centre. J Bone Oncol. 2013;2(4):137-144.
  3. Saad F, Eastham J. Zoledronic acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer. Urology. 2010;76(5):1175-1181.
  4. Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88(5):1082-1090.
  5. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;96:879-882.
  6. Melton LJ, Kyle RA, Achenbach SJ, Oberg AL, Rajkumar SV. Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res. 2005;20(3):487-493.
  7. Saad F, Lipton A, Cook R, Chen Y-M, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer. 2007;110(8):1860-1867.
  8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.7.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed August 8, 2021. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  9. McGrath LJ, Hernandez RK, Overman R, Reams D, Liede A, Brookhart MA. Patterns and predictors of initiation of intravenous bisphosphonates among patients with multiple myeloma in the United States. Blood. 2017;130(Suppl 1):534.
  10. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548.
  11. Yong K, Delforge M, Driessen C, et al. Multiple myeloma: patient outcomes in real-world practice. Br J Haematol. 2016;175(2):252-264.
  12. Knudsen LM, Hippe E, Hjorth M, et al; for the Nordic Myeloma Study Group. Renal function in newly diagnosed multiple myeloma—a demographic study of 1353 patients. Eur J Haematol. 1994;53(4):207-212.
  13. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21-33.
  14. Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomized, controlled, phase 3 study. Lancet Oncol. 2018;19(3):370-381.
  15. Roodman GD. Pathogenesis of multiple myeloma bone disease. Leukemia. 2009;23(3):435-441.
  16. Data on file, Amgen; 2021.