From the Guidelines
Multiple myeloma is diagnosed when a patient has at least one myeloma-defining event (end-organ damage including hypercalcemia, renal failure, anemia, or bone lesions) plus evidence of clonal plasma cells ≥10% on bone marrow examination or a biopsy-proven plasmacytoma, as per the International Myeloma Working Group (IMWG) diagnostic criteria 1.
Diagnostic Criteria
The diagnostic criteria for multiple myeloma include:
- 10% or more clonal plasma cells in the bone marrow (and/or a biopsy proven plasmacytoma)
- Any one or more myeloma defining events (MDE):
- End-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) attributable to the underlying plasma-cell disorder
- Bone marrow clonal plasma cells ≥60%
- Serum involved to uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC level is ≥100 mg/L)
- More than 1 focal lesion (5 mm or more in size) on magnetic resonance imaging (MRI)
Treatment Options
Treatment depends on transplant eligibility.
- For transplant-eligible patients, induction typically includes a triplet regimen such as bortezomib, lenalidomide, and dexamethasone (VRd) for 3-4 cycles, followed by autologous stem cell transplantation and maintenance therapy with lenalidomide.
- For transplant-ineligible patients, regimens include lenalidomide plus dexamethasone (Rd), or bortezomib, lenalidomide, and dexamethasone at reduced doses.
- Newer agents for relapsed disease include daratumumab, carfilzomib, pomalidomide, and isatuximab, often combined with other drugs.
Supportive Care
Supportive care is essential and includes:
- Bisphosphonates for bone disease
- Pain management
- Prophylaxis against infections
Monitoring Treatment Response
Treatment response is monitored through:
- Serum and urine protein electrophoresis
- Serum free light chain assays
- Periodic imaging The choice of therapy should be individualized based on patient factors including age, comorbidities, cytogenetic risk, and previous treatment responses 1.
From the FDA Drug Label
14 CLINICAL STUDIES 14. 1 Newly Diagnosed Multiple Myeloma
Combination Treatment with Lenalidomide and Dexamethasone in Patients Ineligible for Autologous Stem Cell Transplant MAIA (NCT02252172), an open-label, randomized, active-controlled trial, compared treatment with DARZALEX 16 mg/kg in combination with lenalidomide and low-dose dexamethasone (DRd) to treatment with lenalidomide and low-dose dexamethasone (Rd) in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant. Efficacy was evaluated by progression free survival (PFS) based on International Myeloma Working Group (IMWG) criteria.
The diagnostic criteria for multiple myeloma are not explicitly stated in the provided drug labels. However, the treatment options for multiple myeloma are mentioned, including:
- Daratumumab in combination with lenalidomide and dexamethasone (DRd) for patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant 2
- Elotuzumab in combination with lenalidomide and dexamethasone for adult patients with multiple myeloma who have received one to three prior therapies, or in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor 3 Key points to consider:
- The International Myeloma Working Group (IMWG) criteria are used to evaluate efficacy in multiple myeloma trials 2
- Treatment options may vary depending on patient eligibility for autologous stem cell transplant and prior therapies received 2, 3
From the Research
Diagnostic Criteria for Multiple Myeloma
- Multiple myeloma is diagnosed based on the presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia 4.
- Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 4.
- Serum protein electrophoresis (SPEP) is an easy-to-perform laboratory test that can be used for detection and quantification of monoclonal gammopathy and should be recommended as a preliminary test for suspected cases of multiple myeloma 5.
- The diagnosis of multiple myeloma requires increased numbers of immature, abnormal, or atypical plasma cells in the bone marrow; a monoclonal protein in the serum or urine; or characteristic bone lesions 6.
Treatment Options for Multiple Myeloma
- Standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (e.g., bortezomib), an oral immunomodulatory agent (e.g., lenalidomide), and dexamethasone, and is associated with median progression-free survival of 41 months 4.
- Induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients 4.
- High-dose therapy with autologous stem-cell transplantation remains the treatment of choice for patients under age 70 who are otherwise in good health 7.
- For patients who are not candidates for high-dose therapy or who have had a recurrence of multiple myeloma after prior high-dose therapy, there are a number of further conventional treatment options 7.
- Recent therapeutic advances have made the treatment of multiple myeloma both more complex and more costly, with targeted drugs such as proteasome inhibitors and immune modulators prolonging median survival 7.
Staging and Prognosis
- The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features to assess estimated progression-free survival and overall survival 4.
- At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82% 4.
- The staging system has been revised to combine both measures of tumor burden and disease biology, and advances in therapy have resulted in a marked improvement in overall survival 8.