CMMC Sales Training - Myeloma 101 PDF
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Cameron L. Lilly, Ph.D.
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This document provides sales training information on multiple myeloma (MM), covering disease information, testing, treatment strategies, and other relevant details. The training material is targeted toward business development managers (BDMs) or similar roles.
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MM and CMMC training for Sales Disease information, terms, data, and messaging touchpoints Cameron L. Lilly, Ph.D. The CMMC test is a CLIA-validated LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not bee...
MM and CMMC training for Sales Disease information, terms, data, and messaging touchpoints Cameron L. Lilly, Ph.D. The CMMC test is a CLIA-validated LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. What, Why, and How of Today’s Training To Equip BDMs to have better conversations with hematologists Introduce/refamiliarize you with MM biology, testing, and treatment Highlight the relevant clinical data of the CMMC test Provide guidance on how to present this information from a high level overview Relate the CMMC test to known existing pitfalls in the field Familiarize you with the Aptitude presentation deck especially as an example of how to think about messaging Handling objections Pay-off: Bolster your confidence and arsenal around CMMC, to have more successful meetings and win sales Multiple Myeloma General Information, Biology, Treatment, and Testing 2024 Multiple Myeloma Prevalence From the American Cancer Society Anticipated ~35,780 New Cases in 2024 ~12,540 deaths in 2022 Accounts for ~10% of all hematological cancers Median age of diagnosis is 69 years of age Overall risk is 8y Enormous boom in new tools like ClonoSeq FDA and IMS are discussion secondary endpoints as patients in clinical trials are now living so long Plasma Cell Dyscrasias Clonal cancers of antibody-secreting B-Cells (Plasma Cells, PCs) MGUS: Monoclonal Gammopathy of Undetermined Significance (often asymptomatic) Precursor, first stage of the disease development ~1% will progress to Multiple Myeloma Smoldering Multiple Myeloma (often asymptomatic) Second step of the process, more severe disease ~10% of these patients will progress to MM Multiple Myeloma Symptomatic disease End-organ damage from the cancerous cells Disruption of BM environment leads to secondary symptoms: C.R.A.B. Calcinemia (Abnormally high Calcium in the blood) Renal Insufficiency Anemia (lack of normal levels of red blood cells) Bone Lesions Hellerhoff, Wikimedia Commons Challenges in Multiple Myeloma Patients will relapse, requiring monitoring Current treatment goal is go get a complete response and establish remission Monitoring of MM requires repeated bone marrow biopsies Extremely invasive Further injures already disrupted bone health Sometimes initial testing at onset of symptoms which can be late in progression (like Pat’s Case study) Geographical restriction to comprehensive testing facilities Diagnostic Process Diagnostics: Normal blood panel Serum protein levels Blood Calcium Serum protein electrophoresis (SPEP)/Urine protein electrophoresis (UPEP) Dense band of Ig (M-Spike) Free light chain Renal Function Testing X-Ray/CT/MRI Lesions Suspected SMM or MM Patient Complaints General malaise Bone Marrow Biopsy Tiredness % of BM cells that are Plasma Cells by Bone Pain microscopy or IHC FISH for chromosomal risk features Major fracture in a large bone Cytogenetics to reveal chromosomal (femur, vertebral compression translocations and large abnormalities fracture) Neuropathy Symptoms of anemia Therapeutic Pathway First line therapy is always combination therapy Triplet or quadruplet agents Car-T is now approved as second line therapy as of April of this year for Relapsed Refractory MM (RRMM) Bi-specific T-Cell engagers are approved for fourth line and beyond in RRMM Bone Marrow Cancer With Bone Marrow being the home to development of so many kinds of cells, disruption or cancer in the BM is devastating 11 Cells in and from Bone Marrow Many kinds of cells originate from bone marrow cells Red Blood Cells Platelets ALL Immune cells Image source: https://stemcells.nih.gov/sites/all/themes/stemcells_theme/stemcell_includes/2_1.jpg Diagnostic Pathway and Methods BM BM BM Blood/Urine : Protein Electrophoresis Test to separate proteins by size Visualized as bands M-Protein Antibody secreted by the cancer Serum Protein Electrophoresis Electrophoretic separation of serum proteins (incl. antibodies) M-Spike Spike resulting from M-protein accumulation in serum Presented as % of blood protein comprise by the M-protein https://mykindofscience.com/2017/06/11/clinical-perspectives-multi ple-myeloma-and-serum-protein-electrophoresis/ Blood/Urine: Serum Free Light Chain Antibody Light chains unbound to Ig Probed by detection antibodies directed at epitopes hidden when complexed with a heavy chain Measure free Kappa and Lambda light chains Particularly useful in non-secretory disease where M-Spike isn’t present Hungria, et al. Revista Brasileira de Hematologia e Hemoterapia, Volume 38, Issue 1,2016,Pages 37-43, https://doi.org/10.1016/j.bjhh.2015.11.003. Blood: Beta-2 Microglobulin Protein which is part of the Major Histocompatibility Complex-1 Released into blood Measured in serum by ELISA Reported as mass/volume Normal Range: 0.7-1.8 ug/mg Prognostic in MM, below 4ug/mL is considered favorable Bone Marrow Biopsy Source: cancer.gov BM: Pathology Use chemicals to stain cells from a bone marrow biopsy Image credit: Genevieve M. Crane, M.D., Ph.D., https://www.pathologyoutlines.com/topic/lymphomamyeloma.html BM: Immunohistochemistry Use antibodies (below: Anti-CD138) to stain cells from a bone marrow biopsy Image credit: Genevieve M. Crane, M.D., Ph.D., https://www.pathologyoutlines.com/topic/lymphomamyeloma.html BM: Fluorescent testing Fluoresence In Situ Hybridisation: FISH Source: Shi, Y. et al. Acta Medica Int’l 2015 Vol. 2 (2) 168-174 DOI: 10.5530/ami.2015.5.0 Who Gets Which Tests, Who Gets Treated? With this battery of testing available for patients in these diseases, let’s break down how this is applied in patients 21 Testing and Treatment Breakdown of testing and therapy by disease stage MGUS SMM MM Blood Work YES YES YES Imaging YES YES YES BM Biopsies NO YES YES Treated? NO NO YES The Data Let’s review the test and relevant enumeration data from CMMC in the existing publications Objectives: Learn how to read the figures and how to present them from an overview level, learn the ‘figure drill’ CMMC Capture/Detection on CELLSEARCH® Using 4ml of Peripheral Blood What classifies a cell as a CMMC? Reagent Function A CMMC is a plasma cell that exhibits the phenotypes CD138+, CD38+, DAPI+ and CD19/45-. Anti-CD138 Ferrofluid Plasma Cell Capture Normal Leukocyte Multiple Myeloma Anti-CD38-PE Stains captured PC as a CMMC Anti-CD138 Anti-CD19 Ferrofluid DAPI Nuclear Staining of All Cells Y Y DAPI DAPI Marks other cells which have Anti-CD19/CD45-APC CD138 that are NOT CMMCs Y Y Anti-CD45 Anti-CD38 The CMMC test is a CLIA LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. Foulk, et al. The initial manuscript describing the assay CMMC Detected in Age-Matched Normal, MGUS/SMM and Multiple Myeloma Patients MGUS/ Multiple Normal SMM Myeloma n 52 62 66 CMMC Range 0-6 0-480 0-16814 Mean 0.5 16 1157 % > 1 CMMC 33 58 91 % > 3 CMMC 6 37 76 % > 5 CMMC 2 26 68 % > 10 CMMC 0 18 58 % > 25 CMMC 0 10 47 % > 50 CMMC 0 8 39 % > 100 CMMC 0 3 35 % > 1000 CMMC 0 0 14 SMM/ Normal MM MGUS The CMMC test is a CLIA-validated LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. CMMC in Newly Diagnosed MM Patients 98% of newly diagnosed MM patients had CMMCs Elevated CMMCs at Diagnosis (median of 1111) Response to therapy → lower CMMC than baseline. Patients who relapsed had elevated CMMC levels compared to patients in remission Foulk et. al. Br. J. Haematol. 2017 The CMMC test is a CLIA-validated LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. CMMC Count and Outcomes Progression Free Survival Overall Survival Foulk et. al. Br. J. Haematol. 2017 The CMMC test is a CLIA-validated LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. “The Dutta Paper” The CMMC test is a CLIA-Accredited LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. Aim: Determine the clinical utility of enumeration and genomic analyses of CMMCs in precursor MM to replace BM as a marker of development Peripheral blood from cohort of 261 patients collected on DFCI PCROWD study CMMCs were enriched (CD138+,CD38+) and enumerated using CellSearch platform CMMCs sorted via FACS The CMMC test is a CLIA-Accredited LDT from Menarini Silicon Biosystems. The performance characteristics and safety and effectiveness have not been established and are not cleared or approved by the FDA. CMMCs are Enumerable from the Majority of Patients CMMCs were detected in 82% of Patients 75% of MGUS Patients, 86% of SMM Patients showed CMMCs p