Multiple MyelomaOverview & Case StudiesJanet Brunner-Grady, PA-CTh. Feb. 23, 2017TRAINING & DEVELOPMENT 1 .
Agenda220.127.116.11.5.Revised IMWG diagnostic criteria for MMMyeloma BasicsCase Study #1Case Study #2Case Study #3TRAINING & DEVELOPMENT 2 .
Revised IMWG Diagnostic Criteria forMultiple MyelomaDefinition of Multiple Myeloma:Clonal bone marrow plasma cells 10% orbiopsy-proven bony or extramedullaryplasmacytoma & one or more of the followingdefining events: Evidence of end organ damage attributable tothe underlying plasma cell disorder One or more biomarkers of malignancyTRAINING & DEVELOPMENT 3 .
Revised Diagnostic Criteria forMyeloma- Defining Events Evidence of end organ damage attributable tothe underlying plasma cell disorder– Hypercalcemia: serum calcium 1 mg/dL ( 0.25mmol/L) higher than the ULN or 11 mg/dL ( 2.75mmol/L)– Renal insufficiency: creatinine clearance 40ml/min or serum creat 2 mg/dL ( 177 μmol/L)– Anemia: hemoglobin 2 g/dL ( 20 g/L) below theLLN or a hemoglobin 10 g/dL ( 100 g/dL)– Bone lesions: one or more osteolytic lesions onskeletal x-ray, CT or PET-CTTRAINING & DEVELOPMENT 4 .
Revised Diagnostic Criteria forMyeloma- Defining Events One or more biomarkers of malignancy– Clonal bone marrow plasma percentage 60%– Involved:uninvolved serum free light chain ratio 100– 1 focal lesion on MRI studies (each lesion mustbe 5 mm in size)TRAINING & DEVELOPMENT 5 .
Multiple Myeloma BasicsTRAINING & DEVELOPMENT 6 .
Multiple Myeloma Basics What is considered measurable disease? Serum M-protein / 1 g/dL and/or Urine M-protein / 200 mg/24 hoursFree light chain levels may be used in place ofthe M-protein, provided the involved chain is 10 mg/dL & the κ/λ ratio is abnormal atdiagnosisTRAINING & DEVELOPMENT 7 .
What Baseline to Use When Determining disease status at time of HCTNo relapse or progression atany time between diagnosisand 1st HCT:Use the disease parameters(DP) from diagnosis as thebaseline.TRAINING & DEVELOPMENT 8 .
What Baseline to Use When Patient was treatedfor a relapse orprogression (R/P) inbetween diagnosis &1st HCT:Use the disease parameters (DP) obtained at thetime of relapse or progression (R/P) as the baseline(the baseline is reset to the time of the relapse orprogression)TRAINING & DEVELOPMENT 9 .
What Baseline to Use When Determining disease response to HCTHCT planned as part of theinitial therapy without a priordisease relapse orprogression:Use disease parameters(DP) obtained at diagnosisTRAINING & DEVELOPMENT 10 .
What Baseline to Use When Determining best response to HCTPatient had a treated diseaseprogression or relapse (R/P)prior to HCT:Use disease parameters(DP) obtained at time of therelapse or progression (R/P)TRAINING & DEVELOPMENT 11 .
What Baseline to Use When . Patient has not received any therapywithin 6 months of HCT or has anuntreated relapse or progression (R/P)Use the diseaseparameters (DP)obtained prior tothe start of prep todetermine bestresponse to HCT.TRAINING & DEVELOPMENT 12 .
What Baseline to Use When .Recipient undergoes aTandem transplant.Tandem transplants areconsidered part of“one” treatment plan.The baseline to usefollowing the 2nd HCTwould be the samebaseline used for the1st HCT providedthere has not been adisease progressionor relapse inbetween.TRAINING & DEVELOPMENT 13 .
Summary of Which Baseline to UseWhen Determining Disease StatusHas there been arelapse orprogression?Disease Status atTime of HCTDiseaseResponse to HCTNo R/PDP at diagnosisDP at diagnosisYes R/P (treated)DP at R/PDP at R/PYes R/P (untreated) DP prior to the start DP prior to start ofof prepprepR/P relapse or progression, DP disease parametersTRAINING & DEVELOPMENT 14 .
Confirmatory Testing Requirements Includes SPEP/UPEP, serum/urineimmunofixation & κ/λ free light chains Confirmatory testing does not apply to BMbiopsies, skeletal surveys & otherradiographic studiesTRAINING & DEVELOPMENT 15 .
Confirmatory Testing Requirements Every disease response (sCR, CR, nCR,VGPR, PR & SD) requires two consecutiveassessments (by the same method) made atany time before the initiation of any newtherapy. Progressive disease (PD) & relapse from CRare a bit different .PD & relapse from CR requires two consecutiveassessments (by the same method) beforeclassification, and/or the start of any new therapy.TRAINING & DEVELOPMENT 16 .
Confirmatory Testing Requirements To report CR, both the serum & urineimmunofixation must be negative as well asconfirmed! Many institutions don’t obtain urine studies ona regular basis. CR may be reported as long as there is atleast one negative serum & one negativeurine immunofixation and one of them isconfirmed.TRAINING & DEVELOPMENT 17 .
Multiple Myeloma Complete Remission (CR) criteriaTRAINING & DEVELOPMENT 18 .
Multiple MyelomaQuestion- If a patient had a BMBx with 5%plasma cells prior to HCT, but did not meet theother CR criteria (e.g., serum IFE for IgGlambda), can the same BMBx be used postHCT when evaluating for CR status?TRAINING & DEVELOPMENT 19 .
Multiple Myeloma Answer- Yes! A repeat BMBx is not neededsince the plasma cells were already 5%.TRAINING & DEVELOPMENT 20 .
MYELOMA CASE STUDIESTRAINING & DEVELOPMENT 21 .
Myeloma Case Study #1A 55 year old AA male is diagnosed with IgG lambdamyeloma. Results of the initial work-up include: Serum M-spike 4 g/dL (or 4000 mg/dL) 24-hr urine M-protein 1000 mg/24 hr Bone marrow aspirate 60% plasma cellsPatient receives 2 cycles of Revlimid & Dex, then reevaluated: Serum M-spike 2000 mg/dL 24-hr urine M-protein 195 mg/24 hrTRAINING & DEVELOPMENT 22 .
Myeloma Case Study #1What is the patient’s disease response after twocycles of Rev/Dex?A) Very Good Partial Remission (VGPR)B) Partial Remission (PR)C) Stable Disease (SD)TRAINING & DEVELOPMENT 23 .
Myeloma Case Study #1The patient’s PR status was confirmed with a 2ndmeasurement. The patient received twoadditional cycles of Rev/Dex & re-evaluated fordisease response. Serum M-spike 2900 mg/dL 24-hr urine M-protein 600 mg/24 hr Bone marrow aspirate 30% plasma cellsTRAINING & DEVELOPMENT 24 .
Myeloma Case Study #1What is the patient’s disease response after a totalof 4 cycles of Rev/Dex?A)B)C)D)Very Good Partial Response (VGPR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)TRAINING & DEVELOPMENT 25 .
Myeloma Case Study #1Patient is switched to Vincristine, Adriamycin &Decadron (VAD) and is re-evaluated after twocycles. Serum M-spike 1400 mg/dL24-hr urine M-protein 190 mg/24 hrBone marrow aspirate 15% plasma cellsThe patient achieved a PR after two cycles of VAD.The plan is to give IV Cytoxan mobilization.TRAINING & DEVELOPMENT 26 .
Myeloma Case Study #1What studies were used as a baseline to makethat determination?A) The studies obtained at diagnosisB) The studies obtained after first two cycles ofRev/DexC) The studies obtained at time of progressionTRAINING & DEVELOPMENT 27 .
Myeloma Case Study #1The patient has undergone their autologousPBSC HCT & has been evaluated monthly forthe 1st three months post HSCT. Day 30 evaluation:Serum M-spike 1000 mg/dLSerum immunofixation ( ) for IgG lambda24-hr urine M-protein 190 mg/24 hrsBone marrow biopsy 7% plasma cellsTRAINING & DEVELOPMENT 28 .
Myeloma Case Study #1Day 60 evaluation: SPEP/UPEP- no monoclonal band Serum/Urine immunofixation ( ) for IgGlambda 24-hr urine for M-protein 90 mg/24 hrsTRAINING & DEVELOPMENT 29 .
Myeloma Case Study #1Day 100 evaluation: SPEP/UPEP- no monoclonal bandSerum/Urine immunofixation ( ) for IgG lambda24-hr urine for M-protein 0 mg/24 hrsBone marrow aspirate 5% plasma cellsTRAINING & DEVELOPMENT 30 .
Myeloma Case Study #1What is the best disease response to HCT thatyou would report at Day 100 for this patient?A)B)C)D)E)Stable Disease (SD)Partial Remission (PR)Very Good Partial Remission (VGPR)Near Complete Remission (nCR)Complete Remission (CR)TRAINING & DEVELOPMENT 31 .
Myeloma Case Study #2Light Chain only myeloma Malignant plasma cells make only the light chaincomponent of the antibodyLight chains are most often excreted in the urineLab studies include urine protein electrophoresis(UPEP), urine immunofixation electrophoresis(UIFE) and serum free light chain (FLC)TRAINING & DEVELOPMENT 32 .
Myeloma Case Study #2 John D. was diagnosed with Kappa lightchain only myeloma in February 2015. Labsincluded––––––SPEP 0 mg/dL; SIFE negativeUPEP 750 mg/dL; UIFE ( ) kappa light chainsSFL Kappa 200 mg/dL & Lambda 2.0 mg/dLSFL K/L ratio 100240 urine M-protein 600 mg/24 hoursBMBx plasma cells 45%TRAINING & DEVELOPMENT 33 .
Myeloma Case Study #2 Planned treatment included 6 cycles oflenalidomide & dexamethasone. Labs wereobtained prior to start of each cycle.Labs3/14/15/17/16/1SPEP2/1Diagnosis0 g/dLSIFEnegativenegativeUPEP750 mg/dL50 mg/dL250 mg/dLUIFE kappa LC kappa LC kappa LC240 urine600 mg/240175 mg/240SFL Kappa200 mg/dL12075301570SFL Lambda2 mg/dL21.5684SFL K/L ratio100605051.8817.5**Difference19811873.524766% plasma cells45%Lenalid/DexCycle #10 g/dL8%Cycle #2Cycle #3Cycle #420%Cycle #5On holdTRAINING & DEVELOPMENT 34 .
Myeloma Case Study #2 The patient was re-evaluated on 5/1/15 after3 cycles of lenalidomide & dexamethasone?What is the disease response at this time point?A) Partial Response (PR)B) Very Good Partial Response (VGPR)C) Near Complete Remission (nCR)D) Stable Disease (SD)TRAINING & DEVELOPMENT 35 .
Myeloma Case Study #2 The patient’s disease was re-evaluated on7/1/15, prior to the start of cycle 6.What is the disease response at this time point?A) Partial Response (PR)B) Stable Disease (SD)C) Progressive Disease (PD)TRAINING & DEVELOPMENT 36 .
Myeloma Case Study #2 Free Light Chain results & how to use them A PR response requires a 50% decrease in thedifference between the involved & uninvolved lightchains. A VGPR response requires a 90% decrease in thedifference between the involved & uninvolved lightchains. Progressive disease (PD) requires a 25% increasefrom the lowest response value achieved with anabsolute increase 10 mg/dL in the differencebetween the involved & uninvolved light chains.TRAINING & DEVELOPMENT 37 .
Myeloma Case Study #2 Therapy was switched to bortezomib7/18/19/110/150 mg/dL250 mg/dL50 mg/dL0 mg/dL0 mg/dL kappa LC kappa LC kappa LC kappa LC kappa LC kappa LC240 urine600 mg/240175 mg/240SFL Kappa200 mg/dL301570201215SFL Lambda5 mg/dL6845610SFL K/L ratio40451.8817.5421.5**Difference195247661565% plasmacellsBortezomib45%8%Labs5/1SPEP2/1Diagnosis0 g/dLSIFEnegativenegativeUPEP750 mg/dLUIFE6/10 g/dLCycle #4Len/Dex0 mg/24020%Cycle #5Len/DexCycle #17/15/154%Cycle #28/15/15Cycle #39/15/15Cycle #410/15/15TRAINING & DEVELOPMENT 38 .
Myeloma Case Study #2 PBSCs were collected & patient underwent an Auto HCTon 5/160 mg/dLnegativeUPEP250 mg/dL50 mg/dL0 mg/dL0 mg/dL0 mg/dL0 mg/dL0 mg/dLUIFE kappa LC kappa LC kappa LC kappa LC kappa LCnegativenegative240 urine0 mg/2400 mg/240SFL Kappa70201215127.7510SFL Lambda45610101215SFL K/L % plasmacells20%4%2%**** Clonal plasma cells absent based on immunohistochemistryTRAINING & DEVELOPMENT 39 .
Myeloma Case Study #2 What was the patient’s disease status prior tothe start of conditioning?A) VGPRB) nCRC) CRD) SD (stable disease)TRAINING & DEVELOPMENT 40 .
Myeloma Case Study #2 What was the recipient’s disease status atthe Day 100 evaluation?A) VGPRB) nCRC) CRD) sCRTRAINING & DEVELOPMENT 41 .
Myeloma Case Study #3 Jane D. is a 61 yo AA woman diagnosed withIgA kappa myeloma. Results from herdiagnostic work-up include IgG 361; IgA 7120; IgM 25 mg/dl SPEP 4.5 g/dl M-protein (Beta-2)1.0 g/dl M-protein (Gamma) SIFE ( ) IgA kappa BM plasma cells 45%TRAINING & DEVELOPMENT 42 .
Myeloma Case Study #3TRAINING & DEVELOPMENT 43 .
Myeloma Case Study #3 Laboratory tests measuring M-protein In general, serum M-protein is measured usingdensitometry on SPEP. The SPEP may be unreliable in patients with IgAmyeloma, as the monoclonal proteins can migratein the beta region. IgA quantitative immunoglobulin levels onnephelometry or turbidometry can be used toassess a disease response in place of the SPEP.TRAINING & DEVELOPMENT 44 .
Myeloma Case Study #3 Jane is treated 2 cycles of vincristinedoxorubicin-dexamethasone (VAD) andrepeat labs are obtained IgA 2400 mg/dl SPEP 1.75 g/dl M-protein (Beta-2)0.25 g/dl M-protein (Gamma) SIFE ( ) IgA kappaTRAINING & DEVELOPMENT 45 .
Myeloma Case Study #3 Jane is treated 4 cycles of vincristinedoxorubicin-dexamethasone (VAD). Labs areobtained prior to start of PBSC collection IgA 500 mg/dl SPEP 0.5 g/dl M-protein (Beta-2)0 g/dl M-protein (Gamma) SIFE ( ) IgA kappa BM plasma cells 7%TRAINING & DEVELOPMENT 46 .
Myeloma Case Study #3 What is Jane’s disease response prior to thePBSC collection?A.B.C.D.PRVGPRnCRCRTRAINING & DEVELOPMENT 47 .
Myeloma Case Study #3 Jane is 3 months post autologous HCT andlabs obtained prior to her office visit included IgA 350 mg/dL (WNL) SPEP 0 g/dL SIFE ( ) IgA kappa UPEP 0 mg/dL; UIFE negative BM plasma cells 4%TRAINING & DEVELOPMENT 48 .
Myeloma Case Study #3 What is Jane’s disease response at 100 dayspost auto HCT?A.B.C.D.PRVGPRnCRCR49 .TRAINING & DEVELOPMENT 49
Myeloma Case Study #3 Jane is 6 months post autologous HCT andlabs obtained prior to her office visit included IgA 300 mg/dL (WNL) SPEP 0 g/dL; SIFE negative UPEP 0 mg/dL; UIFE negative All results have been confirmedTRAINING & DEVELOPMENT 50 .
Myeloma Case Study #3 What is Jane’s disease response at 6 monthspost auto HCT?A.B.C.D.PRVGPRnCRCRTRAINING & DEVELOPMENT 51 .
QuestionsTRAINING & DEVELOPMENT 52 .
24-hr urine M-protein 1000 mg/24 hr Bone marrow aspirate 60% plasma cells Patient receives 2 cycles of Revlimid & Dex, then re-evaluated: Serum M-spike