MC Community Event: How Multiple Myeloma Affects the Black Community with Dr. Craig Cole

Dr. Craig Cole, a Black multiple myeloma specialist at the MSU (Michigan State University) Breslin Cancer Center, joined the African American Myeloma Chapter within the Myeloma Crowd Community program to share with us biological, cytogenetic, and therapeutic differences seen in African Americans with multiple myeloma, as well as the need for African Americans to enroll in clinical trials. 

The presentation provided by Dr. Cole was both entertaining and informative. We invite you all to watch the video and/or read the detailed transcript about the event below. You won't want to miss the amazing information shared by an expert in the world of myeloma. 

• What is Myeloma and how common is it? 
  • Myeloma is the cancer of plasma cells, myeloma consists of abnormal plasma cells that become malignant and produce an excessive amount of what we know as the m-protein
  • Multiple Myeloma is the 2nd most common blood cancer
  • There were 32,270 new cases of myeloma diagnosed in 2020
  • There are approximately 131,392 myeloma patients living in the U.S. who are living with or in remission from myeloma 
  • Myeloma is most frequently diagnosed in people 65 to 74 years old 
• Race/Ethnicity and Myeloma
  • Data from the National Cancer Registry shows the overall incidence of multiple myeloma is slightly higher in men at 8.8 per 100,000 than women at 5.7 per 100,000. 
  • However, in African Americans, these numbers increase significantly with African American men are diagnosed at 16.5 per 100,000 and African American women at 12.0 per 100,000. 
  • While the national population of African Americans within the United States is only at 13.4%, if we look at the US myeloma population by ethnicity, we see that Black myeloma patients make up for 19% of the United States myeloma population, because this disease has more prevalence with African Americans. 
  • Blacks have more than twice the myeloma incidence of whites. This mirrors the higher incidence of MGUS. 
  • Global studies show a significant disparity in the incidence of this disease with 11.6 Blacks (men and women combined) out of 100,000 being diagnosed with myeloma, compared to All Races combined having an incidence of 5.29 people per 100,000 being diagnosed.
  • This means Blacks have the highest risk of myeloma of any race/ethnic group in the world.  
• Risk Factors for Multiple Myeloma 
  • There is no conclusive evidence for multiple myeloma being an inherited disease
  • The racial difference in incidence cannot be explained by tobacco or alcohol use, or socioeconomic status
  • Obesity increases the risk, but this is independent of the risk with African Americans 
  • Exposure to ionizing radiation is the most convincing risk factor for multiple myeloma, as well as chemical exposures over long periods of time (diesel exhaust, pesticides, etc.) 
• Differences in African American Myeloma 
  • This is a very active area of research- figuring out why myeloma is so different between the races 
  • In both races (black and white) and both genders, incidences of myeloma have been increasing while mortality has been declining over the last 20 years. 
  • There are biological differences presented in African Americans
    • African American generally present with multiple myeloma four years younger than their Caucasian counterparts 
    • Black patients with multiple myeloma demonstrate more anemia and higher serum lactate dehydrogenase (LDH) levels
    • African Americans more commonly have IgH translocations than those with European ancestry: t(11:14), t (14:16)
      • t (11;14) is the target for the new drug Venetoclax in clinical trials, t (11;14) is a standard risk genomic feature 
    • African Americans are less likely than whites to have TP53/17 p deletions (these are high-risk genomic features)
    • Recent data shows that under equal opportunity treatment settings (the VA system), African Americans may have a better survival rate with myeloma 
• Knowing your myeloma labs 
  • CBC: number of red blood cells, white blood cells, and platelets 
  • CoMP: measure levels of albumin, calcium, and creatinine. Assess the function of kidney, liver, and bone status as well as the extent of the disease 
  • Beta2 MicroG: determine for the level of a protein that indicates the presence/extent of MM and kidney function: USED FOR STAGING MYELOMA 
  • LDH (lactate dehydrogenase): determine the level of myeloma cell productions and the extent of MM: USED FOR STAGING MYELOMA 
  • Serum Protein EP: detect the presence and level of M protein = how much myeloma there is and whether the treatments are working 
    • eliminates the need for bone marrow biopsies every month! 
  • Immunofixation: identifies the type of abnormal antibody proteins: IgG, IgA, kappa or lambda 
  • Serum FreeLight Chain: Freelite test measure free light chains (kappa or lambda) in blood= how much myeloma there is 
    • Normal kappa/lambda ratio should be 1:1 
    • Ratio is increased when myeloma (plasma) cells are present 
  • Urine Protein EP: detect Bence-Jones proteins (otherwise known as myeloma light chains) in urine (present or not present) 
  • 24-hr Urine Analysis: determine the presence and levels of m-protein and Bence Jones protein in the urine= how much myeloma there is 
• Types of Monoclonal Protein (m-protein) in multiple myeloma 
  • Intact immunoglobulin 
    • IgG+ kappa 
    • IgG+ lambda 
    • IgA+ kappa 
    • IgA+ lambda 
    • etc.
    • 80% of myeloma cases 
  • Light Chain only 
    • Also known as Bence Jones protein 
    • 20% of all myeloma cases 
    • Renal failure more common in light chain myeloma
  • Non-secretory 
    • no monoclonal protein present 
    • 3% of cases in multiple myeloma 
• Making the myeloma diagnosis 
  • Conventional x-rays reveal punched-out lytic lesions, osteoporosis, or fractures in 75% of patients 
  • FDG PET/CT appears to be more sensitive than x-rays for the detection of small lytic bone lesions (85% of patients) 
  • Diagnosis is confirmed with bone marrow demonstrating greater than 10% involvement by malignant plasma cells. 
  • Is it then determined whether you have MGUS, Smoldering Myeloma, or active Multiple Myeloma 
    • MGUS:
      • m protein under 3 g/dL
      • plasma cells in bone marrow under 10%
      • no CRAB or high-risk features
      • 1% risk of progression per year to myeloma or related conditions 
      • Monitored for changes by the treating physician 
    • Smoldering Myeloma (SMM): 
      • m protein over 3 g/dL
      • plasma cells in bone marrow between 10-60% 
      • no CRAB or high-risk features 
      • 10% risk of progression per year to active myeloma 
      • close monitoring for changes from treating physician, clinical trials encouraged 
    • Multiple Myeloma (active disease) 
      • m protein + malignant plasma cells are seen on any biopsy 
      • and >1 CRAB feature 
        • C: calcium elevation (>11 mg/dL) 
        • R: renal- low kidney function; (serum creatinine >2 mg/dL)
        • A: anemia- low red blood count (Hb <10 g/dL) 
        • B: bone disease (>1 lytic lesions on skeletal radiography, CT, or PET-CT) 
      • or if you have >1 high-risk features (these patients are treated) 
        • plasma cells in bone marrow >60%
        • serum-free light chain ratio over 100 
        • 1 or more MRI lesion
      • Patients that fit these criteria are started on induction treatment 
    • The higher risk of multiple myeloma in Black is likely a result of the higher prevalence of the premalignant MGUS stage, there is so data to suggest that Blacks have a higher progression rate of MGUS to myeloma
• Staging myeloma and risk biology 
  • The Importance of Genomic Testing: What are the mutations? This can be found in the FISH test. 
  • Patients are broken up into two groups depending on the results of their FISH test results: high-risk and standard risk 
  • High risk: deletion 17 chromosome, 1q gain chromosome, translocation (4;14), translocation (14;16), translocation (14;20), mutations in p53 gene on chromosome 17, successful treatments don't last as long in high-risk patients 
  • Standard risk: hyperdiploid (more than 1 pair of chromosomes), translocation (11;14), translocation (6;14), etc. Standard-risk patients are known to have longer remissions compared to high-risk myeloma patients. 
  • Staging refers to the degree to which the cancer has progressed
    • Stage 1: b2 microglobulin under 3.6 mg/L, Normal LDH, no high-risk cytogenetics 
    • Stage 2: doesn't fit criteria for Stage 1 or Stage 3 
    • Stage 3: b2 microglobulin over 5.5 mg/L, High LDH (more likely in Black patients) and/or high-risk cytogenetics 
• Goals of Therapy: Dr. Cole showed an image of an iceberg representative of how we want to "bury" the multiple myeloma. 
• Application of Science in Treatment 
  • There are different categories of drugs used in the myeloma arsenal
    • Immunomodulatory drugs (IMiDs): Thalomid (Thalidomide), Revlimid (Lenalidomide), Pomaylst (Pomalidomide) 
      • How do they work?
        • direct inhibition of DNA synthesis of myeloma cells 
        • inhibition of blood vessel synthesis in the bone marrow 
        • inhibition of adhesion between myeloma and bone marrow stromal cells 
        • starves the myeloma cells by inhibiting the release of the cytokines IL-6, TNF-a, and IL-1B
        • activation of the body's natural killer cells (T-cells) which attack the myeloma cells 
    • Proteasome Inhibitors (Pis): Velcade (Bortezomib), Ninlaro (Ixazomib), Kyprolis (Carfilzomib)
      • How do they work? 
        • Uses the protein metabolism of myeloma cells against them 
        • The proteasome is an organelle found in all cells but really prevalent in myeloma cells (who produce high amounts of protein) 
        • When myeloma cell proteins have served their function and get degraded, it goes to the proteasome which acts as a garbage disposal and shoots the used protein out of the cell 
        • Proteasome inhibitors essentially fill up those proteasome garbage disposals with "cement" thus blocking the proteasome from being able to do its job
        • This creates an extreme build-up of protein within the cell and the myeloma cells cease to function and blow up 
    • Antibodies against myeloma (Immunotherapy treatments): Darzalex (Daratumumab), Sarclisa (Isatuximab), Empliciti (Elotuzumab)
      • On myeloma plasma cells, there are certain proteins that identify which cells are malignant plasma (myeloma) cells. 
        • These proteins are: SLAMF7, CD40, CD138, CD38, BCMA 
        • Because our bodies don't produce antibodies for these proteins, they have been created in the lab 
        • CD40: antibody drugs are dacetuzumab, lucatumumab 
        • SLAMF7: antibody-drug is Elotuzumab (Empliciti) 
        • CD138: antibody-drug is Indatuximab or Ravtansine 
        • CD38: antibody-drug is Daratumumab (Darzalex) or Isatuximab (Sarclisa) 
        • BCMA: Benlantamab, CAR T therapies, bi-specific antibodies 
      • So how do they work? 
        • Antibodies attach to the myeloma cell and call in the immune system (white cells), the white cells fire granules at the malignant plasma (myeloma) cells and kill them 
        • Increases production of cytotoxic T-cells 
        • Complement protein attack myeloma cells 
        • attacks the myeloma cell biology (they cross circuit the signaling pathways inside the cell) 
        • inhibition of adhesion between the myeloma and bone marrow stromal cells 
        • Adding Dara to RVD has shown incredible depth in response in high-risk transplant-eligible with newly diagnosed MM 
    • Other novel therapies: XPOVIO (selinexor), BLENREP (belentamab mafodotin), Pepaxto (melflufen or melphalan flufenamide) 
    • More to come...
• Induction, Transplant, and Maintenance 
  • There are numerous different regimens to use as induction therapies. 
  • When patients are newly diagnosed, the treating physician should determine whether or not this patient is a candidate for stem cell transplant or not 
  • Non-transplant candidates, depending on their risk factors, are usually given VRd or Dara-Rd (this will vary on your treating physician, it is highly recommended you consult a multiple myeloma specialist before deciding) 
  • Transplant candidates are given Dara-Rd, VRd or KRd, again this depends on your genomic risk factors 
  • Dr. Cole gives personal clinical protocols about what induction therapies, transplant timings, and maintenance are used in his clinic. 
  • Dr. Cole strongly recommends stem cell transplants for his patients if they qualify.
  • African American patients are less likely to receive an SCT (stem cell transplant) compare with white patients, even after controlling for age, gender, socioeconomic status, insurance provider, and comorbidity score. 
  • If a doctor doesn't offer a transplant, please seek out a second opinion. 
  • Studies show there is no difference in time to relapse (PFS) or Overall Survival in standard-risk patients who have two transplants, consolidation RVD therapy, or just straight to maintenance after the first SMT
    • going straight to maintenance is the easiest 
    • if you have high-risk myeloma, a tandem transplant (one right after the other) might be right for you 
  • Revlimid maintenance therapy has proven to be most successful and is the one that Dr. Cole recommends for his patients 
  • The duration of time that you should be on maintenance therapy has not been confirmed, at least 36 months is recommended
• New Therapies in Relapsed Myeloma 
  • There are so many breakthroughs and advancements happening in relapsed myeloma, this is thanks to those that participate in clinical trials and allow these medicines to be tested. 
  • A great example of this is the BELLINI trial that tests Venetoclax+Velcade+Dex which proved to be incredibly successful for translocation (11;14) patients in terms of progression-free survival. Black myeloma patients have a higher incidence of translocation (11;14) than any other ethnic group. 
  • Car T cell Therapy is another new and upcoming therapy for relapsed myeloma 
    • T-cells are a type of white blood cell that attacks and kills viruses and cancer cells 
    • Chimeric antigen receptors (CARs) help T-cells recognize and destroy cancer cells 
    • Program the patient's T-cells with CAR to recognize and destroy the patient's own cancer cells 
• Clinical Trials 
  • Clinical trials are rigorously controlled research studies that test whether a new treatment is safe and/or effective against cancer 
  • Clinical trials also test whether a new treatment is better or the same at treating specific cancers than the most current treatment available
  • Patients get a lot of attention and support 
  • Patients are watched closely by their doctor, as well as other members of their medical team, to ensure their safety 
  • The FDA looked at approvals for new drug application submitted between 2003-2017
    • The median enrolled percentage of Black was 4.5%
    • So how do we know if these treatments are going to work on African Americans? The biology is different, and we need to know if the drugs work for this ethnic group. This is why we NEED more Black myeloma patients to enroll in clinical trials. 
  • Patients of minority race with myeloma have had less increase in population-level survival in the early 21st century than white patients 
  • Survival of minorities is similar to that of white when enrolled in clinical trials 
  • We need appropriate representation in myeloma clinical trials to ensure that new drugs will work equally as well for African American myeloma patients
  • Every year, clinical trials are getting more effective and safer. The results replace the previous standard of care for a better working treatment. 
  • The goal is for this to continue each year until we find the cure for myeloma. It's possible! 

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