Forms Revision: Myeloma Changes

Transcription

1 Sharing knowledge. Sharing hope. Forms Revision: Myeloma Changes J. Brunner, PA-C and A. Dispenzieri, MD February 2013

2 Disclosures Janet Brunner, PA-C I have no relevant conflicts of interest to disclose. Angela Dispenzieri, MD I have no relevant conflicts of interest to disclose.

3 Objectives: 1) Understand why the Myeloma & Amyloid Forms were combined into one 2) Complete the revised Pre/Post-HCT Plasma Cell Disorder (PCD) forms accurately

4 Plasma Cell Disorder (PCD)- Pre-HCT Data Form 2016

5 Subsequent HCT Additional options have been added: Same disease subtype, but without a prior disease insert completed (begin with Q1) Same disease subtype, but there has been a relapse or progression (begin with Q188- Was therapy given?) Same disease (begin with Q233)

6 Plasma Cell Disorders (PCD) Additional sub-types have been added Osteosclerotic myeloma / POEMS syndrome Light chain deposition disease (LCDD) Question about preceding / concurrent PCD Multiple myeloma (symptomatic) Smoldering myeloma (asymptomatic) Monoclonal gammopathy of unknown significance (MGUS)

7 How to report Myeloma and Amyloidosis Scenario 1 Patient has smoldering myeloma (asymptomatic) & amyloidosis. Report amyloidosis as the primary diagnosis for HCT (question 1). Report smoldering myeloma as a concurrent diagnosis (question 6)

8 How to report Myeloma & Amyloidosis Scenario 2 Patient has symptomatic myeloma & amyloidosis Report symptomatic myeloma as the primary diagnosis for HCT (question 1) Report amyloidosis as a concurrent diagnosis (question 6)

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10 Bone marrow Blood stream Antibodies Immunoglobulins Fight infection Myeloma Plasma cells Eat away at bones Crowd bone marrow causing anemia Harmful Use a.k.a. Monoclonal antibody M-protein M-spike Myeloma protein Immunoglobulin Ig Myeloma: Poison kidneys Amyloid: Deposit in various organs causing disease LCDD Similar to amyloid

11 Asymptomatic vs. Symptomatic Myeloma Criteria for Spectrum of MGUS MM Non-IgM Monoclonal protein No End Organ Damage?* M-spike 3 g/dl OR BMPC 10%? No Yes Monoclonal gammopathy (MGUS) Inactive MM (smoldering MM) Yes Active or symptomatic MM End organ damage without other explanation Calcium Renal Anemia Bones Other Intern. Myeloma Working Group, Br J Haem 121, , 2003

12 Bone marrow Blood stream Myeloma protein Little protein secreted Oligosecretory Myeloma cells Light chain secreted (no heavy chain) Most myeloma cases No protein secreted Non-secretory Bence Jones Or light chain myeloma

13 Light chain only myeloma vs. LCDD Light chain only myeloma is merely a type of MM (no heavy chain). It may cause light chain cast nephropathy (renal failure) Light chain deposition disease (LCDD) is actually very similar to amyloidosis except looks slightly different under microscope

14 Glomerulus Proximal tubule Kidney & Plasmaproliferative Disorders Distal tubule Glomerulopathies AL amyloidosis Light chain deposition disease Tubulointerstitial Cast nephropathy (myeloma kidney) Type II cryo (diffuse MPGN) Fibrillary GN Acquired Fanconi s syndrome Light chains + Tamm Horsfall Protein = light chain cast nephropathy

15 Staging of Myeloma Durie-Salmon Staging Requires hemoglobin, serum calcium, monoclonal protein & bone survey findings International Staging System (ISS) Requires β 2 microglobulin & albumin

16 International Staging System Stage Criterion Stage I Stage II Stage III 2 M < 3.5 mg/l and alb 3.5 g/dl Not Stage I or III 2 M 5.5 mg/l Greipp P R et al. JCO 2005;23:

17 Durie Salmon Staging System Stage I Stage III All of the following One or more of the following Hemoglobin > 10.0 g/dl Hemoglobin < 8.5 g/dl Serum calcium < 12 mg/dl Serum calcium > 12 mg/dl On radiograph, normal bone structure or Advanced lytic bone lesions solitary bone plasmacytoma only Low M-component production rates High M-component rates IgG < 5 g/dl, IgA < 3 g/dl, or urine IgG > 7 g/dl, IgA > 5 g/l, or urine light M spike on electrophoresis < 4 g/24 hrs chain M spike > 12 g/24 hrs Stage II Fitting neither stage I or III A: Serum creatinine < 2 mg/dl B: Serum creatinine 2 mg/dl

18 International Durie Salmon Staging System Staging System IIA 909/ (54,61) Greipp P R et al. JCO 2005;23:

19 Cytogenetics FISH Conventional

20 IFM Tandem Transplant 513 Pts Risk by FISH and beta-2 microglobulin B2M LT4 LT4 FISH Nml 13 GT4 GT4 LT4 Nml 13 4;14; 17p GT4 4;14, 17p Avet-Loiseau, H. et al. Blood 2007;109: Copyright 2007 American Society of Hematology. Copyright restrictions may apply.

21 Metaphase Cytogenetics FISH for t(11;14)

22 Genetic Risk in Multiple Myeloma Standard Risk* Intermediate High Risk FISH t(11;14) t(6;14) Hyperdiploid t(4;14) del17p t(14;16) t(14;20) Other All others Cytogenetic deletion 13 Or hypodiploidy Or PCLI>3% GEP High Risk Signature Dispenzieri et al. Mayo Clin Proc 2007;82: ; Kumar et al. Mayo Clin Proc : v7 Revised and updated: Jan

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24 Laboratory Studies This section has been expanded to include: Gene Expression Profile

25 Gene Expression Profiling (GEP) Measures activity (the expression) of thousands of genes at once, to create a global picture of cellular function. GEP can distinguish between cells that are actively dividing, or show how the cells react to a particular treatment.

26 Gene expression patterns can distinguish risk groups in training cohort. Shaughnessy J D et al. Blood 2007;109: by American Society of Hematology

27 Amyloidosis Section Cardiac biomarkers (current) Brain natriuretic peptide (BNP) and/or N-terminal prohormone brain natriuretic peptide (NT-proBNP) Troponin

28 Amyloidosis Cardiac biomarkers (revised form) Brain natriuretic peptide (BNP) N-terminal prohormone brain natriuretic peptide (NTproBNP) Troponin I Troponin T High sensitivity troponin T

29 Cardiac Biomarkers BNP- secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes) Troponin- integral to muscle contraction in skeletal & cardiac muscle. It is the most specific & sensitive laboratory markers of myocardial cell injury

30 Significance of Cardiac Biomarkers in AL Troponin T < ug/l* NT-proBNP < 332 ng/l* (N=127) (N=182) (N=174) Stage 1: Neither high Stage 2: Either high Stage 3: Both high *Dispenzieri et al J Clin Oncol ;22(18): Kumar et al, Mayo Clinic Proc, (1):12-8.

31 Proportion surviving Validation of the criteria of response to treatment in AL amyloidosis Palladini G, Dispenzieri A, Gertz MA, et al. New Criteria for Response to Treatment in Immunoglobulin Light Chain Amyloidosis Based on Free Light Chain Measurement and Cardiac Biomarkers: Impact on Survival Outcomes. Journal of clinical oncology. 2012;30(36): p<0.001 CR (97 patients, 3.6 deaths/100 py) VGPR (233 patients, 9.6 deaths/100 py) PR (140 patients, 23.7 deaths/100 py) NR (179 patients, 47.2 deaths/100 py) Time (months) p<0.001 p=0.01 Survival of 649 patients based on hematologic response at 6 months 0.2 NT-proBNP progression (at least 300 ng/l and 30% increase), 169 patients 0.1 NT-proBNP stable, 108 patients NT-proBNP response (at least 300 ng/l and 30% decrease), 100 patients Time (months) Proportion surviving p<0.001 p<0.001 Survival of 377 patients with baseline NTproBNP 650 ng/l according to NT-proBNP response and progression at 6 months

32 Pre-HCT Therapy Added common regimens: VCD (Bortezomab, cyclophosphamide, dexamethasone) RVD/VRD (Bortezomab, lenilidomide, dexamethasone) DVD/VDD (Bortezomab, liposomal doxirubicin, dexamethasone)

33 Best Response to Therapy Near Complete Remission (ncr) added Serum & urine M-protein detectable by immunoelectrophoresis (IFE) Negative SPEP & UPEP <5% plasma cells in bone marrow.

34 Plasma Cell Disorder (PCD) Post-HCT Data Form 2116

35 Disease Specificity Determination Q1- Was the recipient transplanted for or do they have a history of amyloidosis? If yes, go to Q2 If no, go to Q3 (best response question) Q2- Did the recipient have features of multiple myeloma? If yes, go to Q3 If no, go to Q5 (lab studies at best response)

36 Laboratory Studies Section Lab Studies at Time of Best Response to HCT Questions 5-33 Completed for both Amyloidosis & Multiple Myeloma

37 Hematologic & Organ Evaluation Section Questions Completed for Amyloid only patients; or Multiple Myeloma patients with a history of or concurrent diagnosis of Amyloid

38 Post-HCT Therapy Not using planned vs. not planned terminology Q60- Was therapy given since the date of last report for reasons other than relapse or progressive disease? (include any maintenance and consolidation therapy)

39 Questions