Criteria for Disease Assessment Joan Bladé

Transcription

1 Criteria for Disease Assessment Joan Bladé Unidad de Amiloidosis y Mieloma Servicio de Hematología Hospital Clínic de Barcelona COMy Meeting, París, May 4th, 2018

2 Response Evaluation EBMT, CR and progression IMWG Uniform Criteria scr, VGPR IMWG updated, MRD (flow cytometry, NGS) - Imaging (PET/CT) Bladé et al, 1998, Durie et al, 2006; Kumar et al, 2016

3 EBMT criteria for response, relapse and progression in MM

4 EBMT, IBMTR, ABMTR Criteria for Definition of Response, Relapse and Progression in Patients With Multiple Myeloma Treated by High-dose Therapy and Stem Cell Transplantation Response Category* CR PR MR Stable disease Criteria Negative IF (serum and urine)** <5% bone marrow plasma cells Disappearance of soft tissue plasmacytomas 50% serum M-protein 90% urine M-protein or < 200 mg/24hrs 50% soft tissue plasmacytomas 25-49% serum M-protein 50-89% urine M-protein 25-49% soft tissue plasmacytomas Not meeting criteria for MR nor PD *All response categories must be maintained for at least 6 weeks ** Excluding oligoclonal bands

5 EBMT, IBMTR, ABMTR Criteria for Definition of Response, Relapse and Progression in Patients With Multiple Myeloma Treated by High-dose Therapy and Stem Cell Transplantation Response Category PD* Relapse from CR* Criteria 25% and >5 g/l serum M-protein 25% and >200 mg/24h urine M-protein Bone marrow plasma cells >25% and absolute increase >10% New lytic lesions, plasmacytomas or hypercalcaemia Paraprotein reappearance (IF or EP) (excluding oligoclonal reconstitution) Bone marrow plasma cells > 5% New lytic lesions, plasmacytomas or hypercalcaemia *Confirmed on at least one repeated sample

6 International Uniform Response Criteria for Multiple Myeloma Durie et al, Leukemia 2006; 20:

7 International Uniform Response Criteria for Multiple Myeloma (I) Response Category* CR scr VGPR PR Criteria Negative IF (serum and urine) <5% bone marrow plasma cells Disappearance of soft tissue plasmacytomas As above plus Normal sflc ratio Absence of clonal plasma cells** 90% serum M-protein Urine M-protein<100 mg/24h 50% serum M-protein 90% urine M-protein or < 200 mg/24hrs 50% soft tissue plasmacytomas * All response categories require two consecutive measurements made at any time ** A minimum of 3000 plasma cells analyzed by multiparametric flow cytometry (with 4 colors) Durie et al, Leukemia 2006

8 IMWG definition of measurable disease and recommended measurements Definitions of measurable disease Response criteria to all categories of response except CR are aplicable only to patients who have measurable disease defined by at least one of the following measurements: Serum M-protein 10 g/l Urine M-protein 200 mg/24h Involved FLC level 100 mg/l plus an abnormal FLC ratio Measurement of the M-protein Serum M-protein: quantitated using densitometry on SPEP, unless than SPEP is unrelaible, which should be explicitly reported Urine M-protein: quantitated using 24h-UPEP only Patients with measurable disease should be followed monthly by both SPEP and UPEP for response assessment while on therapy

9 International Uniform Response Criteria for Multiple Myeloma (II) Response Category* Stable disease Criteria Not meeting criteria for CR, VGPR, PR or PD PD 25% and >5 g/l serum M-protein * 25% and >200 mg/24h urine M-protein * Difference between involved and uninvolved FLC levels must increase > 100 mg/l Bone marrow plasma cells >25% and absolute increase >10% New lytic lesions, plasmacytomas or hypercalcaemia * All response categories require two consecutive measurements made at any time Durie et al, Leukemia 2006

10 Suggested Modifications of the International Uniform Response Criteria for Multiple Myeloma (Consensus panel, IMW 2009 and 2011) Response Category MR (relapsed/refractory myeloma) Immunophenotypic CR Molecular CR Criteria 25-49% serum M-protein 50-89% urine M-protein 25-49% soft tissue plasmacytomas Stringent CR plus Absence of phenotypically aberrant plasma cells* Stringent CR plus Negative ASO-PCR** * Minimum of 1 million total BM cells analyzed by MFC with 4 colors **Sensitivity 10-5

11 Suggested Modifications of the International Uniform Response Criteria for Multiple Myeloma (Kyle & Rajkumar, Leukemia 2009) Response Category* Relapse from CR* Criteria Paraprotein reappearance (IF or EP) (excluding oligoclonal reconstitution) >5 g/l serum M-protein >200 mg/24h urine M-protein Bone marrow plasma cells > 5% New lytic lesions, plasmacytomas or hypercalcaemia PD 10 g/l are sufficient to define relapse if starting M- component is 50 g/l

12 Response to Treatment Fernández de Larrea et al. Leukemia 2013

13 Multiple Myeloma Workup 1. Complete blood count and differential; peripheral blood smear 2. Chemistry screen, including creatinine, calcium, LDH, beta2-microglobulin 3. Serum protein electrophoresis and immunofixation 3. Serum immunoglobulins (nephelometric quantification) 4. Measurement of serum free light chain (FLC) hour urine collection for electrophoresis and immunofixation 6. Bone marrow aspirate: morphology, immunophenotype and cytogenetics by FISH (13q, t(11;14); t(4;14); t(14;16); 17p) 7. Radiologic skeletal survey CT and/or MRI if clinically needed 11. PET/CT in patients with suspected extramedullary disease

14 Monitoring of Patients under Active Therapy Induction and/or Maintenance Before every cycle CBC, chemistry including serum EP and 24-hours protein urine excretion with EP If EP negative serum and urine IF and, if negative, bone marrow aspirate in order to confirm CR

15 Follow-up in Patients with Multiple Myeloma Off-Therapy After conventional therapy: (patients with stable response) After HDT/SCT: First year: every 2 months Beyond first year: every 3 months Beyond 5 years: every 4 months First 6 months: every 2 months Two first years: every 3 months From 2 to 5 years: every 4 months Beyond 5 years: every 6 months

16 Patients with asymptomatic relapse or PD* After conventional therapy: every 2 months After HDT/SCT: every 3 months * Unless abrupt PD

17 Lab work-up during follow-up off therapy 1. Complete blood count and chemistry 2. Serum total protein and EF hours urine protein measurement with EF 4. Serum and urine immunofixation and serum FLC every 2 visits only in patients in CR 5. Bone marrow aspirate and/or imaging techniques only when clinically indicated Bone marrow: unexplained cytopenias (medullary progression, MDS) Imaging: bone or extramedullary progression

18 Oligoclonal Bands 1. Monoclonal protein original 2. In patients in CR (ASCT, novel therapies) 3. Faint small bands in the gamma region, usually non-quantifiable 4. More frequent: IgG-k, IgG-, IgM (k or ), k or light chains, rarely IgA 5. Frequently multiple and fluctuating 6. Never show a significant increase 7. Tipically persistent all along the CR duration and their disappearance usually precedes relapse

19 Response Evaluation EBMT, CR and progression IMWG Uniform Criteria scr, VGPR IMWG updated, MRD (flow cytometry, NGS) - Imaging (PET/CT) Bladé et al, 1998, Durie et al, 2006; Kumar et al, 2016

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