Can You Identify This Multiple Myeloma Patient’s R-ISS Stage?
Are you up to date on the revised international staging for multiple myeloma? How about appropriate consolidation therapy? Test your knowledge on these topics and more in our latest quiz.
Are you up to date on the revised international staging for multiple myeloma? How about appropriate consolidation therapy? Test your knowledge on these topics and more in our latest quiz.
Question 1
A 62-year-old male presents to his primary care physician with severe lower back pain after working in his yard. Radiographs show compression fractures of the L3 and L4 vertebra. Complete blood count shows a normal platelet and white blood count, but hemoglobin is 9.3 with mean corpuscular volume of 94. Additional labs show a calcium of 11.6, total protein 9.2, albumin 3.7, and creatinine 1.6. Serum protein electropheresis shows a monoclonal paraprotein measuring 4.5 g/dL with serum immunofixation positive for an IgG lambda paraprotein. Beta-2 microglobulin is 3.4 and lactate dehydrogenase (LDH) is normal. Bone marrow biopsy reveals 60% monoclonal plasma cells. Fluorescent in situ hybridization studies show a translocation between chromosomes 4 and 14.
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Answer
B. R-ISS stage II. The R-ISS staging system uses the same factors considered in the ISS stage system (beta-2 microglobulin and albumin) but also takes into account the patient’s LDH and the presence or absence of high risk genetic features. Patients with a beta-2 microglobulin < 3.5 and an albumin > 3.5, with a normal LDH and no high-risk genetic features are classified as stage I. Patients with a beta-2 microglobulin > 5.5 and an elevated LDH or high-risk genetic features are classified as stage III. Patients not falling into stages I or III are classified as stage II.
Question 2
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Answer
B. Progression-free survival benefit but no overall survival benefit.A prospective clinical trial evaluated 700 patients with newly diagnosed multiple myeloma who were treated with 3 cycles of RVD induction and then randomized to either 5 additional cycles of RVD consolidation with no transplant or autologous stem cell transplant followed by 2 additional cycles of RVD. Both groups received lenalidomide maintenance for 1 year. The median progression-free survival was significantly longer in the group that underwent upfront transplantation (50 vs 36 months). Overall survival at 4 years did not differ between the two groups. It should be noted that lenalidomide maintenance was not continued indefinitely in this arm of the French trial, which is the usual practice in the United States. The US portion of the trial in which lenalidomide is continued indefinitely has completed accrual but the results are not yet reported.
Question 3
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Answer
D.There is no PFS or OS benefit with tandem ASCT or RVD consolidation post single ASCT compared with single ASCT followed by maintenance lenalidomide. The phase III STAMINA trial studied transplant eligible multiple myeloma patients who had already received upfront therapy. Patients were then randomized to single ASCT followed by 4 RVD consolidation cycles followed by lenalidomide maintenance until progression (ACM), tandem ASCT followed by lenalidomide maintenance until progression (TAM), or single ASCT followed by maintenance lenalidomide until progression (AM). At the data cutoff, 38-month probabilities of PFS were 57%, 56%, and 52% for ACM, TAM, and AM. Corresponding probabilities of OS were 86%, 82%, and 83%. The conclusion was that neither the addition of RVD consolidation nor second ASCT was superior to a single ASCT followed by lenalidomide maintenance.
Question 4
A 65-year-old man with IgG kappa multiple myeloma is treated with 4 RVD induction cycles and achieves a very good partial remission. He is then treated with melphalan 200 mg/m2 and autologous stem cell transplantation and achieves a complete response. He is placed on lenalidomide maintenance and is followed at 3-month intervals with CBC, CMP, serum protein electropheresis , urine protein electrophoresis, and kappa/lambda free light chains. Four years post-transplant his monoclonal protein rises to 1.3 g/dL and hemoglobin drops to 10.2 g/dL. A bone marrow biopsy is performed and shows recurrent myeloma with 40% involvement by monoclonal plasma cells. The patient is started on a combination of daratumumab, lenalidomide, and dexamethasone.
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Answer
D. The rate of progression-free survival at 12 months is superior with daratumumab, lenalidomide, and dexamethasone.The phase III POLLUX study evaluated 569 patients with relapsed multiple myeloma who had received one or more prior lines of therapy. Patients were randomized to either lenalidomide and dexamethasone alone (control) or lenalidomide and dexamethasone combined with daratumumab. The rate of progression-free survival at 12 months was 83% in the daratumumab group compared with 60% in the control group. There was a significantly higher rate of overall response (92.9% vs 76.4%) in the daratumumab group along with a higher rate of CR (43.1% vs 19.2%). At 12 months the rates of overall survival were similar between the two groups (92% vs 87%) with follow-up for long-term survival ongoing.
Question 5
A 43-year-old female with no significant past medical history presents to her primary care physician with shortness of breath, watery diarrhea for 2 months, and 20-lb unintentional weight loss. Labs show a hemoglobin of 9.8 with a normal mean corpuscular volume. She is referred for colonoscopy and biopsies with Congo red staining, which reveals extensive amyloid deposition throughout the colon. Mass spectrometry is diagnostic of amyloid light-chain (AL) amyloidosis. Serum protein electropheresis shows an m-spike of 0.4 g/dL with immunofixation positive for a lambda FLC. Bone marrow biopsy shows involvement by 2% monoclonal plasma cells. Congo red staining on the bone marrow biopsy is also positive for amyloid deposition. Chemistries reveal a creatinine of 2.1.
Answer
C. Echocardiogram, troponin I and N-terminal pro-brain natriuretic peptide.As AL amyloidosis has been confirmed on biopsy of the colon and bone marrow, biopsy of the kidney and/or submission of bone marrow biopsy for mass spectrometry is unnecessary. In the absence of neurologic symptoms lumbar puncture is not indicated. However, further evaluation to determine whether the patient has cardiac involvement is mandatory. Using cardiac troponin and N-terminal pro-brain natriuretic peptide, patients can be risk-stratified using the Mayo staging system. In patients receiving transplantation as part of their treatment, those with Mayo stage I have a median overall survival not reached at 40 months compared with median overall survival of 8 months in patients with Mayo stage III. Due to the questionable benefit of autologous stem cell transplantation (ASCT) in AL amyloidosis patients with significant cardiac involvement, along with the high risk of transplant related mortality, ASCT is often not performed under these circumstances.
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April 6th 2024The FDA has approved ciltacabtagene autoleucel for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of treatment, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.
Relapsed/Refractory Multiple Myeloma Trial Updates From ASCO 2023
August 7th 2023Experts from Mayo Clinic and The University of Texas MD Anderson Cancer Center discuss results from multiple myeloma trials presented at the 2023 American Society of Clinical Oncology Annual Meeting and how they may apply to clinical practice.
