Smoldering Multiple Myeloma

Transcription

1 Smoldering Multiple Myeloma S. Vincent Rajkumar Professor of Medicine Mayo Clinic Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida Mayo Clinic College of Medicine Mayo Clinic Comprehensive Cancer Center

2 No conflicts to disclose Disclosures

3

4 SMM verus MGUS Kyle RA et al. N Engl J Med 2007;356:

5 Previous Disease Definitions MGUS SMM MM <10% BMPC AND <3gm/dL M protein AND No CRAB 10% BMPC OR 3 gm/dl M protein AND No CRAB Clonal PCPD CRAB attributable to the PCPD No CRAB CRAB CRAB= Hypercalcemia, renal failure, anemia, or lytic bone lesions attributable to a clonal plasma cell disorder Rajkumar SV. Cecil Textbook of Medicine, 25th Edition, 2016

6 Rajkumar SV. Cecil Textbook of Medicine, 25th Edition, 2015 Catch-22

7 Paradigm shift in diagnosis of myeloma

8 Revised IMWG Criteria MGUS SMM MM <10% BMPC AND <3 gm/dl M protein AND No MDE 10%-60% BMPC OR 3 gm/dl S. M protein OR 500 mg/24h Ur. M protein AND No MDE PCPD, AND 1 or more MDE CRAB 60% BMPC 100 FLC ratio >1 MRI focal lesion MDE, myeloma-defining events Rajkumar SV, et al. Lancet Oncol. 2014;15(12):e538-e548.

9 Light Chain SMM Kyle RA, et al. Lancet Haematol 2014;1:e28-36

10 SMM verus MGUS Kyle R et al. N Engl J Med 2007;356:

11 SMM Paradigm Shift MGUS Myeloma

12 Exclude Multiple Myeloma

13 Exclude Lytic Lesions Low-dose Whole Body CT or PET-CT Rajkumar SV, Dispenzieri A. In: Niederhuber JE, et al, eds. Abeloff s Clinical Oncology, 5 th Edition; Rajkumar SV. In: Goldman L and Schafer AI, eds. Goldman s Cecil Medicine, 25 th Edition

14 Bone Marrow Plasma Cell Estimation Regular (Wright s, H & E) Not immunostaining Not flow Highest value Rajkumar SV et al. N Engl J Med 2011; N Engl J Med 2011; 365:

15 FLC Ratio >100 and Risk of progression to myeloma >100 <100 Larsen J, et al. Leukemia advance online publication 27 November 2012; doi: /leu

16 Gonsalves W. Blood Cancer J. 2015;5:e296. Impact of renal failure

17 Using the FLC ratio 100 Measurable level of involved FLC: 100 mg/l ( 10 mg/dl) Be wary of Longstanding history Minimal urine 24 hour M protein Assay Rajkumar SV, Landgren O, Mateos MV. Blood 2015

18 Images courtesy of Jens Hillengass MD. University Hospital Heidelberg, S.D.G.; Hillengass J, Landgren O. Leuk Lymphoma 2013;54:

19 MRI Focal Lesions 23/149 patients had >1 lesion; median TTP not patients with <= 1 FL and 13 months for those with >1 FL Jens Hillengass et al. JCO 2010;28:

20 MRI Definite focal lesions at least 2 5mm Repeat in 3-6 months if in doubt Rajkumar SV, Landgren O, Mateos MV. Blood 2015

21 Merz et al, Leukemia 2014 Evolving MRI findings

22 Diagnosis of Myeloma Judgment Hypercalcemia Renal Failure Anemia Bone Judgment Interpreting FLC ratio Clinical course Imaging studies Rajkumar SV, Dimopoulos M, Palumbo A, et al. Lancet Oncol. 2014;15(12):e538-e548.

23 Smoldering Multiple Myeloma High-Risk SMM MM >60% BMPC FLCr >100 >1 MRI focal lesions Low-risk SMM: 2012 MFMER

24 Smoldering Multiple Myeloma 25%/year risk of MM High-Risk SMM Low-risk SMM: 5%/yr risk of MM 2012 MFMER

25 High Risk SMM: Median TTP ~2 years 10% PCs plus: SMM with M protein 3 gm/dl Absence (<5%) of normal PCs by immunophenotyping plus Immunoparesis Abnormal FLC ratio Del(17p), t4;14, gain(1q21) M protein 4 gm/dl IgA SMM Evolving pattern Increased circulating plasma cells Rajkumar SV, Landgren O, Mateos MV. Blood 2015

26 FLC Ratio and risk of progression in SMM Dispenzieri, A. et al. Blood 2008;111: Copyright 2008 American Society of Hematology. Copyright restrictions may apply.

27 High Circulating Plasma Cells and Risk of progression to myeloma Bianchi, et al. Leukemia advance online publication 18 September 2012; doi: /leu

28 High Plasma Cell Proliferative Rate and Risk of progression to myeloma PCLI 1 PCLI <1 Percent progressing Follow up from diagnosis of smoldering multiple myeloma (years) Madan S. Mayo Clin Proc 2010

29 Cytogenetic Abnormalities and risk of progression in SMM Risk Cytogenetic Abnormalities % of patients (N=351) Median TTP to Multiple Myeloma (months) a Median TTP to Multiple Myeloma or related disorder (months) b High-Risk t(4;14) Del(17p) Gain(1q21)* 13% Intermediate- Risk Trisomies 42% Standard-Risk t(11;14), t(14;16), t(14;20), combined IgH translocations and trisomies, and isolated monosomy 13 30% Low-Risk No abnormalities detected on FISH 15% Not reached 101 Rajkumar SV et al Leukemia Aug;27(8): ; Neben et al. J Clin Oncol 2013

30 FISH Abnormalities Neben et al, JCO 2013 High risk: any of del(17p13), t(4;14), or 1q21

31 Evolving M protein Levels Risk factor Progression within 2 years emp only 64% ehb only 65% Both emp and ehb 82% emp, ehb, and BMPC 20% 91% emp: 10% increase in M protein within 6 months (if M-protein 3 g/dl) or 25% increase in M protein within 12 months (minimum 0.5 g/dl) ehb: 0.5 g/dl decrease within 12 months Ravi P, et al. Blood Cancer J 2016;6:e454-

32 Fernández de Larrea C, et al. Leukemia 2018 (epub)

33 Management of SMM

34 When Should Treatment Be Initiated? Potential New Myeloma or Smoldering Myeloma Any Myeloma Defining Events? CRAB, >60% PC, FLC >100, MRI >1 focal No Myeloma Defining Events (SMM) High Risk SMM (Median TTP ~2 years) Low Risk SMM (~5% per year PD) Especially Evolving, or Many high risk factors Treat as Myeloma To Treat or Not to Treat? Observation Rajkumar SV, Landgren O, Mateos MV. Blood 2015