Objectives Multiple Myeloma Understand the eligibility and purpose - PDF document

Objectives Multiple Myeloma • Understand the eligibility and purpose and MGUS of hematopoietic stem cell transplantation for myeloma. Craig Hofmeister, M.D. • Understand who will benefit from intravenous bisphosphonates and the Assistant Professor of Medicine most common complications. OSU Comprehensive Cancer Center Objectives Epidemiology • Prevalence • Review epidemiology and pathophysiology of multiple myeloma. � Annual incidence about 4 per 100,000 � 19,900 new diagnoses in the United States in • Obtain familiarity with International 2007 Myeloma Working Group criteria to � 10,790 expected deaths diagnose plasma cell dyscrasias. � The average age at diagnosis is 68 years • Be able to describe the most active � 1% diagnosed in individuals aged <40 years drugs for myeloma: IMiDs and proteasome inhibitors. 1. Multiple Myeloma Research Foundation. Causes & incidence. http://www.multiplemyeloma.org/about_myeloma/2.03/php. Accessed May 2, 2007. 3. Multiple Myeloma Research Foundation. Multiple myeloma: disease overview. 2006. http://www.multiplemyeloma.org/downloads/about_myeloma/ Disease_Overview.pdf. Accessed April 30, 2007. 4. American Cancer Society. Detailed guide: multiple myeloma - what are the risk factors for multiple myeloma? http://www.cancer.org/docroot/CRI/content//CRI_2_4_2X_What_are_the_risk_factors_for_multiple_myeloma_30.asp?sitearea=. Accessed April 30, 2007. 1

Epidemiology Epidemiology Estimated Annual Cases in the United States • Population subgroups 2002 2003 2004 2005 2006 2007 � Incidence of multiple myeloma (MM) is twice New Cases 14,600 14,600 15,270 15,980 16,570 19,900 as common in African Americans Deaths 10,800 10,900 11,070 11,300 11,310 10,790 � Slightly more frequent in men than women • Common clinical features include � Bone pain, fractures, osteolytic lesions • 10,960 men; 8940 women (estimated new � Anemia, hypercalcemia cases in 2007) � Renal insufficiency • Remains incurable � Bleeding tendency � Peripheral neuropathy 1. Multiple Myeloma Research Foundation. Causes & incidence. http://www.multiplemyeloma.org/about_myeloma/2.03/php. Accessed May 2, 2007. 3. Multiple Myeloma Research Foundation. Multiple myeloma: disease overview. 2006. http://www.multiplemyeloma.org/downloads/about_myeloma/ Disease_Overview.pdf. Accessed April 30, 2007. 1. American Cancer Society. Cancer facts & figures. 2002. 2003. 2004. 2005. 2006. 2007. http://www.cancer.org. Accessed April 30, 2007. 4. American Cancer Society. Detailed guide: multiple myeloma - what are the risk factors for multiple myeloma? 2. International Myeloma Foundation. Concise review of the disease and treatment options. 2006. http://www.cancer.org/docroot/CRI/content//CRI_2_4_2X_What_are_the_risk_factors_for_multiple_myeloma_30.asp?sitearea=. Accessed April 30, 2007. http://www.myeloma.org/pdfs/ConciseReview2006.pdf. Accessed April 30, 2007. Epidemiology Clinical Presentation • Bone pain Age-specific Incidence Rates for Myeloma, 2000–2003 • Headaches 50 • Bone marrow • Blurry vision 40 Incidence (per 100,000) � Easy bruising • Renal insufficiency 30 � Infection • Hypercalcemia 20 � Anemia � Somnolence 10 � Nausea and vomiting 0 0-24* 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ 1. International Myeloma Foundation. Concise review of the disease and treatment options. 2006. Age in Years *<25 cases for this age group. http://www.myeloma.org/pdfs/ConciseReview2006.pdf. Accessed April 30, 2007. 2. Multiple Myeloma Research Foundation. Multiple myeloma: disease overview. 2006. Source: SEER Cancer Statistics Review 1975-2003, National Cancer Institute, 2006. http://www.multiplemyeloma.org/downloads/about_myeloma/Disease_Overview.pdf. Accessed April 30, 2007. 2

Renal Manifestations Systems Affected • 55%: Myeloma kidney = Cast • Hematologic nephropathy, i.e. tubular casts in the distal nephron � 73% of patients will have anemia • 20% AL amyloidosis secondary to in glomeruli and blood vessels • Marrow infiltration with plasma cells • 20% Monoclonal Ig deposition Congo red birefringence of a disease, most commonly glomerulus when viewed • Decreased levels of erythropoietin through crossed Polaroid filters light-chain deposition disease • 5% Cryoglobulinemic glomerulonephritis & • Decreased erythrocyte survival proliferative glomerulonephritis (rare) Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33. “M-spike” Systems Affected In MM, there is overproduction of one subtype • Skeletal of immunoglobulin, called the M protein � Bone pain is the most common (monoclonal protein) symptom • Osteolytic lesions, generalized osteoporosis, or osteopenia � Associated oncologic emergencies • Spinal cord compression • Hypercalcemia (Not a true emergency) • Renal � M proteins may lead to renal failure Adapted from International Myeloma Foundation. Concise review of the disease and treatment options. 2006. http://www.myeloma.org/pdfs/ConciseReview2006.pdf. Accessed April 30, 2007. Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33. 3

Bone Marrow in Serum Protein Electropheresis Myeloma Monoclonal “spike” Patient beta alpha-2 alpha-1 albumin gamma • BM involvement can be patchy Control • Aspirates can give false negatives _ • Discrepancies between core biopsy and + aspirate not uncommon Urine Protein Electropheresis Hypogammaglobulinemia Serum beta alpha-1 alpha-2 gamma albumin Urine Monoclonal Light Chain Proteinuria 4

Update on diagnosis • Multiple Myeloma • M-protein in serum and/or • Non-secretory myeloma urine OR abnormal FLC ratio • Smoldering myeloma • Κ or λ restricted plasmacytoma or marrow • Plasmacytoma (single or plasma cells multiple) • Related organ or tissue • Plasma cell leukemia impairment • Monoclonal gammopathy… Related organ or tissue dysfunction B uy – Lytic bone lesions C – Hypercalcemia (Ca > 11 mg/dL) A – Anemia (Hb < 10) V – Hyperviscosity I – Bacterial infections (>2) A – Amyloidosis R – Renal (Crt > 1.96 mg/dL) IMWG Diagnostic Criteria . Br J Haemato l. 2003;121:749-757; Leukemia 2006 w/ erratum 2007 Update on diagnosis • No M-component and normal • Non-secretory myeloma FLC ratio • Smoldering myeloma • BmBx clonal PCs ≥ 10% or • Plasmacytoma (single or plasmacytoma multiple) • Related organ or tissue • Plasma cell leukemia impairment • Monoclonal gammopathy… Related organ or tissue dysfunction B uy – Lytic bone lesions C – Hypercalcemia (Ca > 11 mg/dL) A – Anemia (Hb < 10) V – Hyperviscosity I – Bacterial infections (>2) A – Amyloidosis R – Renal (Crt > 1.96 mg/dL) IMWG Diagnostic Criteria . Br J Haemato l. 2003;121:749-757; Leukemia 2006 w/ erratum 2007 5

Update on diagnosis Update on diagnosis • M-protein in serum ≥ 3 g/dL • 20+% circulating monoclonal • Smoldering myeloma and/or clonal PCs on BmBx ≥ plasma cells, ≥ 2000 PCs • Plasmacytoma (single or 10% • Related organ or tissue multiple) • Plasma cell leukemia • NO related organ or tissue impairment • Plasma cell leukemia • Monoclonal gammopathy… impairment • Monoclonal gammopathy… Related organ or tissue dysfunction Related organ or tissue dysfunction B uy – Lytic bone lesions B uy – Lytic bone lesions C – Hypercalcemia (Ca > 11 mg/dL) C – Hypercalcemia (Ca > 11 mg/dL) A – Anemia (Hb < 10) A – Anemia (Hb < 10) V – Hyperviscosity V – Hyperviscosity I – Bacterial infections (>2) I – Bacterial infections (>2) A – Amyloidosis A – Amyloidosis R – Renal (Crt > 1.96 mg/dL) R – Renal (Crt > 1.96 mg/dL) IMWG Diagnostic Criteria . Br J Haemato l. 2003;121:749-757; Leukemia 2006 w/ erratum 2007 IMWG Diagnostic Criteria . Br J Haemato l. 2003;121:749-757; Leukemia 2006 w/ erratum 2007 Update on diagnosis Update on diagnosis • Small M-protein in serum and/or urine if at all • M-protein in serum < 3 g/dL • Κ or λ restricted plasmacytoma(s) • < 10% clonal PCs on BmBx • Plasmacytoma (single or • Single area of bone destruction • No evidence of other B-cell multiple) • No clonal PCs on BmBx lymphoproliferative disorder • Plasma cell leukemia • Monoclonal gammopathy… • NO related organ or tissue • No related organ or tissue • Monoclonal gammopathy… impairment except for adjacent impairment bone if affected Related organ or tissue dysfunction Related organ or tissue dysfunction B uy – Lytic bone lesions B uy – Lytic bone lesions C – Hypercalcemia (Ca > 11 mg/dL) C – Hypercalcemia (Ca > 11 mg/dL) A – Anemia (Hb < 10) A – Anemia (Hb < 10) V – Hyperviscosity V – Hyperviscosity I – Bacterial infections (>2) I – Bacterial infections (>2) A – Amyloidosis A – Amyloidosis R – Renal (Crt > 1.96 mg/dL) R – Renal (Crt > 1.96 mg/dL) IMWG Diagnostic Criteria . Br J Haemato l. 2003;121:749-757; Leukemia 2006 w/ erratum 2007 IMWG Diagnostic Criteria . Br J Haemato l. 2003;121:749-757; Leukemia 2006 w/ erratum 2007 6