Things You Don t Want to Miss in Multiple Myeloma

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1 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

2 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 vs 28% in [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 SEER stat fact sheet: myeloma

3 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

4 Disease Manifestations in Myeloma

5 Interaction between Plasma Cells and Bone Marrow in Multiple Myeloma Palumbo A, Anderson K. N Engl J Med 2011;364:

6 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 < [2] None None 1 CRAB* feature [3] 1. IMWG. Br J Haematol. 2003;121: Kyle RA, et al. Leukemia. 2009;23: Durie BG, et al. Hematol J. 2003;4:

7 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)

8 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

9 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

10 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

11 Symptoms Related To Bone Low blood counts Hypercalcemia Nervous system Renal damage Hyperviscocity Infections

12 Signs and symptoms of light chain amyloidosis Cardiac Enlarged Liver and spleen Enlarged Tongue Skin changes Diarrhea Carpal Tunnel Syndrome

13 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

14 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

15 Diagnostic Workup for Myeloma

16 SPEP and Immunofixation

17 Peripheral Smear and Bone marrow Rouleux Formation H&E Stain CD 138 Stain Smith D, and Yong K BMJ 2013;346:bmj.f3863

18 Imaging Findings in Multiple Myeloma X-RAY CT MRI

19 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

20 Algorithm for the investigation of a newly detected paraprotein Smith D, and Yong K BMJ 2013;346:bmj.f3863

21 International Staging System for Multiple Myeloma Stage 1 β2m <3.5 mg/l Albumin 3.5 g/dl Stage 2 β2m 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.

22 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

23 Thank you for your attention Any questions, Please Contact Sree Chandana, MD, PhD Cell

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