Things You Don t Want to Miss in Multiple Myeloma Sreenivasa Chandana, MD, PhD Attending Hematologist and Medical Oncologist West Michigan Cancer Center Assistant Professor, Western Michigan University School of Medicine
Multiple Myeloma - Basics Plasma cell disorder: calcium elevation, renal dysfunction, anemia, and bone destruction 2 nd most common hematological malignancy Estimated 24,050 cases and 11,090 deaths in 2014 [1] Median age at diagnosis: 69 yrs [2] 5-yr survival has improved substantially (45% in 2004-2010 vs 28% in 1987-1989 [2] ) due to novel agents Sensitive to treatment, but not curable Progression inevitable The future: risk-adapted therapy, individualized treatment 1. American Cancer Society. Cancer facts & figures. 2014. 2. SEER stat fact sheet: myeloma. 2013.
Biology of Multiple Myeloma Cancer of Plasma cells in bone marrow Clonal expansion of abnormal plasma cells Excess production of monoclonal protein Disrupts immune system Destroys and invades surrounding bone Destroys Kidney Disrupts bone marrow function
Disease Manifestations in Myeloma
Interaction between Plasma Cells and Bone Marrow in Multiple Myeloma Palumbo A, Anderson K. N Engl J Med 2011;364:1046-1060.
Spectrum Disorders of Plasma Cell Criteria MGUS [1,2] Smoldering Myeloma [1] Symptomati c Myeloma [1] M-protein < 3 g/dl spike 3 g/dl spike and/or In serum and/or urine [2] Monoclonal plasma cells in bone marrow, % End-organ damage < 10 10 10 [2] None None 1 CRAB* feature [3] 1. IMWG. Br J Haematol. 2003;121:749-757. 2. Kyle RA, et al. Leukemia. 2009;23:3-9. 3. Durie BG, et al. Hematol J. 2003;4:379-398.
Updated IMWG Criteria For Diagnosis of Plasma Cell Disorders *C: Calcium elevation (> 11 mg/dl or > 1 mg/dl higher than ULN) R: Renal insufficiency (serum creatinine > 2 mg/dl) A: Anemia (Hb < 10 g/dl or 2 g/dl < normal) B: Bone disease ( 1 lytic lesions on skeletal radiography, CT, or PET-CT)
Myeloma and PCP The Primary Care Physician (PCP) is the first contact for most of the patients with cancer Serves as important role in the detection of symptoms and making diagnosis Vital role in facilitation of initial treatment
Early Recognition is Key Early recognition before they develop significant disease burden is very important Early referral will improve patient outcomes No single test will provide diagnosis
Early Detection is Important Irreversible organ dysfunction can be avoided by timely treatment Early referral to specialist improves disease free survival Morbidity from bone lesions, anemia, renal failure, infections can be decreased
Symptoms Related To Bone Low blood counts Hypercalcemia Nervous system Renal damage Hyperviscocity Infections
Signs and symptoms of light chain amyloidosis Cardiac Enlarged Liver and spleen Enlarged Tongue Skin changes Diarrhea Carpal Tunnel Syndrome
Clinical Features Presence of Monoclonal Protein Bone lesions (lytic or osteoporosis) Anemia Renal failure Hypercalcemia Recurrent infections Neurologic Spinal cord compression Peripheral Neuropathy Hyper viscosity
Triggers That Elicit Ordering Diagnostic Workup For Myeloma Patients with persistent and unexplained bone pain Unexplained peripheral neuropathy, carpal tunnel syndrome, abnormal bleeding, symptoms of hypercalcaemia Unexplained renal insufficiency and failure Lymphadenopathy Hepatosplenomegaly Unexplained Lab abnormalities Elevated blood protein (Total, Globulin) Urinary Protein (Globulin, monoclonal) Hypercalcemia Anemia Renal Insufficiency
Diagnostic Workup for Myeloma
SPEP and Immunofixation
Peripheral Smear and Bone marrow Rouleux Formation H&E Stain CD 138 Stain Smith D, and Yong K BMJ 2013;346:bmj.f3863
Imaging Findings in Multiple Myeloma X-RAY CT MRI
Early Diagnosis is the goal, but what are the challenges Keeping Myeloma in the differential and look for monoclonal protein Patients usually have non-specific Symptoms Laboratory results Most common abnormalities include elevated total Protein, low albumin, elevated creatinine, anemia, osteoporosis
Algorithm for the investigation of a newly detected paraprotein Smith D, and Yong K BMJ 2013;346:bmj.f3863
International Staging System for Multiple Myeloma Stage 1 β2m <3.5 mg/l Albumin 3.5 g/dl Stage 2 β2m 3.5-5.5 mg/l or β22m <3.5 mg/l and Albumin <3.5 g/dl Stage 3 β2m >5.5 mg/l *β2m, beta-2 microglobulin.
Survival Average survival is improving significantly with novel agents (5-8 yrs) But it remains incurable Heterogenoeus disease Up to 90% response rate with new therapies
Thank you for your attention Any questions, Please Contact Sree Chandana, MD, PhD schandana@wmcc.org Cell 269 993 6056