Multiple myeloma is a cancer of plasma cells and is responsible for about 10% of all blood cancers. It is more common in black population and males than females. It is a disease of the elderly and the median age of onset is 66 years, with only 2% cases less than 40 years of age. Multiple myeloma almost always arises from monoclonal gammopathy of undetermined significance and progresses to multiple myeloma at a rate of 1% per year. Smoldering or asymptomatic multiple myeloma is another intermediate stage that has a faster rate of progression of about 10% per year to multiple myeloma.
What Is The Latest Treatment For Multiple Myeloma?
The last decade has seen a lot of advancement in the treatment of multiple myeloma, thus improving the survival of the patients. Chemotherapy and stem cell transplantation are the mainstay of treatment. The commonly used drugs are thalidomide, lenalidomide, bortezomib, melphalan, cyclophosphomide, prednisone, and dexamethasone. In the past few years, newer drugs including pomalidomide, carfilzomib, ixazomib, daratumumab, elotuzumab, and panobinostat have been approved by FDA, which have increased the horizon of multiple myeloma treatment. These drugs can be given as a single therapy or combination therapy. (1)
The common combination therapies are bortezomib, lenalidomide, dexamethasone (VRD), bortezomib, thalidomide, dexamethasone (VTD), bortezomib, cyclophosphamide, dexamethasone (VCD), lenalidomide plus dexamethasone (Rd), melphalan, prednisone, thalidomide (MPT), bortezomib, melphalan, prednisone (VMP), carfilzomib, lenalidomide, dexamethasone (KRd).
The phases of multiple myeloma treatment included initial therapy, stem cell transplantation (if patient is eligible) and maintenance therapy, in addition to treating relapse cases.
Initial Therapy: Earlier melphalan based combination therapy was prevalent; however, it has not been replaced by bortezomib and lenalidomide based drug combinations. Initial therapy is given for 4 cycles before the patient is considered for stem cell transplantation. Patients who are not eligible for stem cell transplantation are given additional 8-12 cycles of initial therapy. VRD or VTD are the preferred regimen for standard and intermediate risk patients; KRd is the preferred regimen for high risk patients, while Rd is the preferred regimen for standard risk and VCD for intermediate risk frail or elderly patients who are ≥75 years of age. (2)
Maintenance Therapy- Lenalidomide is the preferred choice for maintenance in standard risk patients; while bortezomib or bortezomib based maintenance therapy for 1-2 years is preferred for intermediate risk patients. High risk patients are given carfilzomib or bortezomib based maintenance therapy for 2 years. (3)
Treatment For Relapse- Treating relapsed cases of multiple myeloma is complicated. Different combinations and regimens have to be tried. Almost all patients relapse after initial therapy, stem cell transplantation and maintenance therapy after 4 years and approximately after 2.5 years without stem cell transplantation. Relapsed and refractory cases can be treated with bortezomib and lenalidomide based regimens or newer drugs based regimens, which include carfilzomib, pomalidomide, elotuzumab, panobinostat, ixazomib and daratumumab.
Although, these drugs are FDA approved, the treatment of multiple myeloma varies from country to country and depends on the availability of the drugs in that particular country.
Diagnosis For Multiple Myeloma
The diagnostic criteria of multiple myeloma include:
- Clonal bone marrow plasma cells ≥10% or bony or extramedullary plasmacytoma proven by biopsy and
- Clonal bone marrow plasma cell ≥60% and/or
- Involved: uninvolved serum free light chain (FLC) ratio ≥100 and/or
- >1 focal lesions on MRI (size should be ≥5 mm) and/or
- Evidence of end organ damage (CRAB criteria)
- Hypercalcemia: Serum calcium >1 mg/dl higher than upper limit of normal or >11 mg/dl
- Renal insufficiency: Creatinine clearance <40 ml/min or serum creatinine >2 mg/dl
- Anemia– Hb >2 g/dl below the lower limit of normal or Hb <10 g/dl
- Bone lesions- One or more bony lesions on skeletal radiography, CT, PET-CT
The work up required for multiple myeloma include CBC, serum calcium, serum creatinine, serum FLC assay, serum and urine protein electrophoresis with immunofixation, and bone marrow examination. Imaging techniques used are CT, FDG-PET/CT, and MRI.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223450/\ Rajkumar SV, Kumar S. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc. 2016;91(1):101–119. doi:10.1016/j.mayocp.2015.11.007
- Rajkumar SV, Harousseau JL. Next-generation multiple myeloma treatment: a pharmacoeconomic perspective. Blood. 2016;128(24):2757–2764. doi:10.1182/blood-2016-09-692947 http://www.bloodjournal.org/content/128/24/2757
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