MYE FORMS REVEALED RESPONSE CODES OBJECTIVES. Stringent Complete Response (scr) Complete Response (CR) I have no conflicts of interest to disclose

Transcription

1 I have no conflicts of interest to disclose MYE FORMS REVEALED Janet Brunner, PA-C CIBMTR MKE New10_1.ppt OBJECTIVES 1) Be able to describe the criteria required for each myeloma response code 2) Be able to identify the appropriate baseline studies to use when determining response to therapy for myeloma patients 3) Be able to report the proper response code when two consecutive assessments have not been obtained during the same reporting period RESPONSE CODES New10_2.ppt Complete Response (CR) Negative immunofixation on serum and urine samples (this is required) Disappearance of any soft tissue plasmacytomas and <5% plasma cells in the bone marrow (confirmation with repeat marrow biopsy not needed) Stringent Complete Response (scr) Negative immunofixation on serum and urine samples (this is required) Disappearance of any soft tissue plasmacytomas and <5% plasma cells in the bone marrow (confirmation with repeat marrow biopsy not needed) PLUS.. 1

2 Normal free light chain ratio, and Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence Very Good Partial Response (VGPR) Serum & urine M-protein detectable by immunofixation, but not on electrophoresis (i.e. SPEP or UPEP) or >90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours Partial Response (PR) >50% reduction in serum M-protein and Reduction in 24-hour urinary M-protein by >90% or to <200 mg/24 hours Stable Disease (SD) Not meeting the criteria for CR, VGPR, PR or PD Progressive Disease (PD) Requires one or more of the following: Increase of >25% from baseline in serum M- protein and/or an absolute increase >0.5 g/dl Increase of >25% from baseline in urine M- protein and/or an absolute increase >200 mg/24 hours For recipients without measurable serum & urine M-protein levels: an absolute increase of >10 mg/dl in the difference between involved & uninvolved free light chain levels Relapse from CR (Rel) Requires one or more of the following: Reappearance of serum or urine M- protein by immunofixation or electrophoresis Development of >5% plasma cells in the bone marrow Appearance of any other sign of progression (e.g. new plasmacytomas, lytic bone lesion, hypercalcemia) 2

3 Definition of Measurable Disease Measurable disease is defined by at least one of the following three measurements: Serum M-protein >/= 1 gram/dl (based on SPEP and not SIFE) Urine M-protein >/=200 mg/24 hrs Serum FLC assay: Involved FLC level >/=10 mg/dl provided the serum FLC ratio is abnormal Measurable vs. non-measurable disease is determined at diagnosis What happens when you have a patient without measurable disease? When trying to determine a PR, a >50% reduction in plasma cells is required in place of the M-protein, provided the baseline bone marrow plasma cells was >30% In addition, a >50% reduction in the size of soft tissue plasmacytomas is also required, if present at baseline. Reporting a Response Code Reporting a response code (scr, CR, VGPR, PR, SD or PD) requires two consecutive assessments made at any time before the institution of any new therapy & no evidence of progression or new bone lesions if radiographic studies were performed; Note- radiographic studies are not required to satisfy scr, CR, VGPR, PR, SD or PD requirements. continued Relapse requires two consecutive assessments made at any time before classification as relapse, and/or the institution of any new therapy What is the proper response code to report when two consecutive assessments have not been obtained in the same reporting period? Keep in mind the six week interval between consecutive assessments is no longer required 3

4 Example A 60 year old WM receives an Auto PBSC HSCT for Multiple Myeloma. At Day +100, it is determined that he has achieved a VGPR in response to the HSCT. He s monitored on a monthly basis & on the last set of labs obtained at the time of his 6 month f/u visit he now meets the criteria for CR. He s doing well and does not return for f/u until 3 months later. Labs at that time confirm that he is in CR. He remains in CR for 2 more years. What is the proper response code to report at 6 months? A) Very Good Partial Remission (VGPR) B) Partial Remission (PR) C) Complete Remission (CR) D)Stable Disease (SD) Survey says (A) When there hasn t been a second assessment in the same reporting period to confirm the response, you report the disease status that was previously confirmed. In this example, you would report VGPR at 6 months. At 1 year, you would report the CR & the date when the CR was first documented. In other words, even though documentation of response requires a confirmatory measurement, the start time for date of response is the first date at which the response was noted. Case #1 Case Studies Patient received planned maintenance therapy (Revlimid) starting on Day 100. A F2116 (Myeloma Post-HSCT) comes due at 6 months. Q20- Was planned treatment per protocol given since the date of the last report? YES (Revlimid) Q Best response to line of therapy need to be answered. What baseline studies would you use to determine the response he/she may have had to the Revlimid? 4

5 Case #1 A) Use the labs obtained prior to starting Revlimid B) Use the labs obtained at diagnosis C) Use the labs obtained immediately prior to the start of the preparative regimen for HSCT Survey says.. (B) Case #2 A patient is diagnosed with IgG kappa myeloma. M-spike =6000 mg/l (from SPEP) 24-hr urine M-protein = 1000 mg/24 hrs Bone marrow biopsy had 40% plasma cells. Patient was treated with Velcade, Doxil & Dexamethasone for 4 cycles Patient was re-evaluated after the 4 th cycle of VDD. The M-spike = 2400 mg/l & there were 15% plasma cells on the bone marrow biopsy. The patient achieved a PR. The patient received Cytoxan for autologous stem cell mobilization. The next set of labs were obtained immediately prior to the start of the prep regimen. The M-spike = 1600 mg/l & 8% plasma cells were noted on the bone marrow biopsy. What is the patient s disease status immediately prior to the start of the preparative regimen? A) Stable Disease (SD) B) Very Good Partial Remission i (VGPR) C) Partial Remission (PR) D)I don t know- not enough information provided to make determination Survey says.. (C) Case #3 The recipient from case #2 has had their autologous HSCT. Lab studies are obtained at 60 & 100 days post HSCT. SPEP/UPEP are negative for an M-spike at Day 60 & 100 Serum & Urine Immunofixation are positive for IgG kappa at Day 60 & 100 Bone marrow biopsy <5% plasma cells at Day 100 Case #3 What disease response code would you report for this recipient at 100 days post-hsct? A) Partial Remission (PR) B) Very Good Partial Remission i (VGPR) C) Complete Remission (CR) D) None of the above Survey says.. (B) 5

6 A 55 year old AA male is diagnosed with IgG lambda myeloma. Results of the initial work-up include- Serum M-spike = 4000 mg/l 24-hr urine M-protein = 1000 mg/24 hr Bone marrow biopsy = 60% plasma cells Patient receives 2 cycles of Revlimid & Dexamethasone & then re-evaluated Serum M-spike = 2000 mg/l 24-hr urine M-protein = 190 mg/24 hr What is the patient s disease response after two cycles of Rev/Dex? A) Partial Remission (PR) B) Very Good Partial Remission (VGPR) C) Stable Disease (SD) Survey says (A) The patient s PR status was confirmed with a 2 nd measurement. The patient received two additional cycles of Rev/Dex & then re-evaluated for disease response. Serum M-spike = 2900 mg/l 24-hr urine M-protein = 600 mg/24 hr Bone marrow biopsy = 30% plasma cells What is the patient s disease response after a total of 4 cycles of Rev/Dex? A) Stable Disease (SD) B) Progressive Disease (PD) C) Partial Remission (PR) Survey says (B) Patient is switched to Vincristine, Adriamycin & Decadron (VAD) and is reevaluated after two cycles. Serum M-spike = 1400 mg/l 24-hr urine M-protein = 190 mg/24 hr Bone marrow biopsy = 15% plasma cells The plan is to give IV Cytoxan mobilization. What is the patient s disease response to the 2 cycles of VAD? The patient has achieved a PR after two cycles of VAD. What studies were used as a baseline to make that determination? A) The studies obtained at diagnosis B) The studies obtained at time of progression C) The studies obtained after first two cycles of Rev/Dex Survey says (B) 6

7 The patient has undergone their autologous PBSC HSCT & has been evaluated monthly for the 1 st three months post HSCT. Day +30 evaluation: Serum M-spike = 1000 mg/l Serum immunofixation (+) for IgG lambda 24-hr urine M-protein = 190 mg/24 hrs Bone marrow biopsy = 7% plasma cells Day +60 evaluation: SPEP/UPEP- no monoclonal band Serum/Urine immunofixation (+) for IgG lambda 24-hr urine for M-protein = 90 mg/24 hrs Day +100 evaluation: SPEP/UPEP- no monoclonal band Serum/Urine immunofixation (+) for IgG lambda 24-hr urine for M-protein = 90 mg/24 hrs Bone marrow biopsy <5% plasma cells What is the best disease response to HSCT that you would report at Day +100 for this patient? A) Stable Disease (SD) B) Partial Remission i (PR) C) Very Good Partial Remission (VGPR) D)Complete Remission (CR) Survey says.. (C) Insights from Dr. Hari regarding Formal vs. Practical Response Assessments Many centers are not doing 24-hr urine studies on myeloma patients anymore. Disease response criteria for PR requires a >50% reduction in the serum M-protein and a reduction in the 24-hr urine M-protein by >90% or to <200 mg/24 hrs. How should data managers handle these types of situations? Dr Hari s response.. If the patient s main paraprotein is in the serum, then I tell them to go ahead and use the serum alone for PR vs. no response, etc. If it is CR that we are looking for, then I insist on urine studies. If a 24-hr urine was not done at least a random urine has to be immunofixation (IFE) negative. 7

8 If the patient has light chain only disease & the urine was the major site of disease, one will not be able to assess for a response without urine studies. Currently, the response criteria do not allow serum free light chain studies as a substitute for urine studies. 8