MC Community Event: How Multiple Myeloma Affects the Black Community with Dr. Craig Cole
MC Community Event: How Multiple Myeloma Affects the Black Community with Dr. Craig Cole
Posted May 13, 2021
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
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
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
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
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
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 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!
Want to join our African American Myeloma Chapter? Click the button below!
Audrey joined the Myeloma Crowd as the Community Program Director in 2020. While not knowing much about myeloma at the start, she has since worked hard to educate herself, empathize and learn from others' experiences. She loves this job. Audrey is passionate about serving others, loves learning, and enjoys a nice mug of hot chocolate no matter the weather.