What is the diagnostic workup and prognosis for multiple myeloma?

From the Guidelines

Multiple myeloma workup should begin with laboratory tests and imaging studies, including whole-body low-dose CT or FDG-PET/CT, as recommended by the NCCN guidelines 1. The initial diagnostic workup for patients with suspected multiple myeloma (MM) should include laboratory tests such as complete blood count, comprehensive metabolic panel, serum protein electrophoresis, immunofixation, serum free light chain assay, and 24-hour urine protein electrophoresis. Imaging studies should include either whole-body low-dose CT or FDG-PET/CT, as recommended by the NCCN guidelines 1. Bone marrow biopsy is essential to confirm the diagnosis and assess plasma cell percentage. Cytogenetic testing (FISH) helps identify high-risk features like t(4;14), t(14;16), or deletion 17p. Prognosis is determined using the Revised International Staging System (R-ISS), which incorporates serum albumin, beta-2 microglobulin, LDH levels, and cytogenetic abnormalities, as supported by the ESMO clinical practice guidelines 1. Some key points to consider in the workup and prognosis of multiple myeloma include:

• The importance of identifying high-risk cytogenetic abnormalities, such as t(4;14), t(14;16), or deletion 17p, which are associated with a poorer outcome 1
• The use of the Revised International Staging System (R-ISS) to determine prognosis, which takes into account serum albumin, beta-2 microglobulin, LDH levels, and cytogenetic abnormalities 1
• The role of treatment in improving outcomes, including combination therapy with proteasome inhibitors, immunomodulatory drugs, and dexamethasone, as well as autologous stem cell transplantation and maintenance therapy with lenalidomide 1
• The importance of regular monitoring of disease markers, renal function, and bone health, as well as prophylaxis for infections, thrombosis, and bone disease 1

From the FDA Drug Label

14 CLINICAL STUDIES 14.1 Multiple Myeloma

A prospective, international, randomized (1:1), open-label clinical study (NCT00111319) of 682 patients was conducted to determine whether bortezomib administered intravenously (1. 3 mg/m2) in combination with melphalan (9 mg/m2) and prednisone (60 mg/m2) resulted in improvement in time to progression (TTP) when compared to melphalan (9 mg/m2) and prednisone (60 mg/m2) in patients with previously untreated multiple myeloma Table 10: Summary of Efficacy Analyses in thePreviously Untreated Multiple Myeloma Study Efficacy EndpointBortezomib, Melphalan and Prednisone n=344 Melphalan and Prednisone n=338 Time to Progression Events n (%) 101 (29) 152 (45) Mediana (months)20.7 15 (95% CI) (17.6,24.7) (14.1,17.9) Hazard ratiob 0.54 (95% CI) (0.42,0.70) p-value c 0. 000002 Overall Survivalat Median Follow-Up of 36. 7 Months Events (deaths) n (%) 109 (32) 148 (44) Mediana (months) Not Reached 43.1 (95% CI) (46.2, NR) (34.8, NR) Hazard ratiob 0.65 (95% CI) (0.51,0.84) p-value c 0.00084

The prognosis for multiple myeloma patients can be determined by several factors, including:

• Time to progression (TTP): The study showed that the combination of bortezomib, melphalan, and prednisone resulted in a statistically significant longer TTP compared to melphalan and prednisone alone, with a median TTP of 20.7 months vs 15 months, respectively.
• Overall survival (OS): The study also showed that the combination of bortezomib, melphalan, and prednisone resulted in a statistically significant longer OS compared to melphalan and prednisone alone, with a median OS of 56.4 months vs 43.1 months, respectively.
• Response rate: The study showed that the combination of bortezomib, melphalan, and prednisone resulted in a higher response rate compared to melphalan and prednisone alone, with a complete response (CR) rate of 30% vs 4%, respectively. The workup for multiple myeloma typically includes:
• Blood tests: To evaluate hemoglobin, platelet count, and beta2-microglobulin levels.
• Imaging studies: To evaluate bone lesions and other organ involvement.
• Bone marrow biopsy: To evaluate the presence of myeloma cells.
• Cytogenetic analysis: To evaluate the presence of genetic abnormalities. 2

From the Research

Multiple Myeloma Workup

• The diagnostic workup for multiple myeloma should include a complete blood count with differential, serum chemistries, creatinine, lactate dehydrogenase, and beta2-microglobulin tests, immunoglobulin studies, skeletal survey, and bone marrow evaluation 3.
• Serum protein electrophoresis (SPE) 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 4.
• Immunofixation electrophoresis detection technique can be used for screening M protein in patients with atypical multiple myeloma and can increase the diagnosis accuracy in patients with atypical multiple myeloma 5.

Prognosis

• The prognosis of multiple myeloma is different from that of monoclonal gammopathy of undetermined significance (MGUS), and MGUS must be differentiated from multiple myeloma 4.
• The detection of residual disease in multiple myeloma can be done using serum protein electrophoresis (SPE) and urine protein electrophoresis (UPE) with immunofixation, and negative results for both can obviate the need for bone marrow biopsy for the detection of residual disease by immunohistochemical analysis 6.
• Urine immunofixation electrophoresis and serum free light chain analyses can benefit the diagnosis of multiple myeloma in patients with normal serum total proteins, creatinine, calcium, and hemoglobin 7.

Diagnostic Challenges

• Some patients with multiple myeloma may present with only laboratory abnormalities, such as anemia, renal disease, and elevated protein levels, and may not have typical multiple myeloma laboratory results 3.
• Multiple myeloma should be highly suspected in patients with unexplained bone lesions and with an abnormal serum free light chain κ/λ ratio, even if serum and urine immunofixation electrophoresis results are negative and light chain ratio is normal 7.