Thank you to our sponsors!
IMF Regional Community Workshop
October 19th, 2024 - Agenda
9:00 – 9:15 AM Welcome & Introductions, Robin Tuohy
9:15 – 9:45 AM Myeloma 101, Al-Ola Abdallah, MD
9:45 – 9:55 AM Q&A with Panel
9:55 – 10:40 AM Taking the Reins of Your Multiple Myeloma Care, Teresa Miceli, RN, BSN, OCN
10:40 – 10:50 AM Q&A with Panel
10:50 – 11:00 AM Coffee Break
11:00 – 11:45 AM Frontline Therapy, Attaya Suvannasankha, MD
11:45 – 11:55 AM Q&A with Panel 11:55 AM – 12:40 PM LUNCH
A core mission of the IMF is to provide thorough and cutting-edge education to the
Please be sure to complete your program evaluation today.
Questions 1 – 5 can be completed before the program begins.
Questions 7 & 8 can be worked on after each presentation.
Our team will collect all responses at the end of the day!
We greatly appreciate your time and feedback!
Kansas City Multiple Myeloma Support Group
Meets Virtually on the 3rd Thursday of each month at 7pm Central
Northwest Arkansas Multiple Myeloma Support Group
Meets hybrid on the 1st Wednesday of each month at 11am Central
Central Nebraska Multiple Myeloma Support Group
Meets hybrid on the 3rd Wednesday of each month at 10am Central
Greater St Louis Area Multiple Myeloma Support Group
Meets virtually on the 1st Wednesday of each month at 7pm Central
Northeast Oklahoma Multiple Myeloma Support Group
Meets hybrid on the 1st Thursday of each month at 11:30am Central
Des Moines Multiple Myeloma Support Group
Meets virtually on the 2nd Thursday of every other month at 5:15pm Central
Special interest groups are designed as a supplemental support for specific populations of patients, in addition to their local Support Groups
Las Voces de Mieloma
Designed for Spanish speaking patients only
Living Solo & Strong with Myeloma
Designed for patients without a care partner
Care Partners Only
Designed to address the needs of care partners only
High Risk Multiple Myeloma
Designed to address the needs of the high-risk MM population
Smolder Bolder
Created for people living with Smoldering Multiple Myeloma
MM Families
For patients/care partners with young children
Myelo is an AI-powered chatbot serving as the International Myeloma Foundation's virtual assistant for patients, care partners, and healthcare professionals.
• Online platform for cancer patients, focusing on clinical trials
• Specializes in multiple myeloma and related blood cancers
• Simplify the process of finding relevant clinical trials
• Empower patients with information about treatment options
• Features:
• Clinical trial search engine
• Personalized trial matching
• Educational resources on clinical trials
More than 1 year since diagnosis
Stem cell transplant recipient
Less than 1 year diagnosed
Care Partner for someone with Myeloma
Al-Ola Abdallah, MD
University of Kansas Medical Center
Kansas City, KS
Associate Professor of Medicine
Chair, US Myeloma Innovations Research Collaborative (USMIRC)
Director, Plasma Cell Disorder Clinic
Division of Hematologic Malignancies and Cellular Therapeutics
Department of Internal Medicine
The University of Kansas Cancer Center
10/19/2024
• 2nd most common hematologic malignancy
• Median age at diagnosis 65 years
• Accounts for 1-2% of all malignant disease • Incidence stable but prevalence rising • Myeloma is thought to evolve most commonly from MGUS
1st
April 15th, 1844, she was admitted to St. Thomas' Hospital in London after her right arm had fractured.
Her treatment was:
• Infusion of orange peel
• An opiate at night
• Wine and arrow-root
“The bones had a red grumous matter.” Thick and lumpy, as clotting blood
• Associated with Agent Orange exposure, benzene, radiation exposure
• Higher incidence in farmers, wood and leather manufactures
• Small Inherited Risk
– Familial Cases exit,1q and 4q loci regions of interest for germinal genetic mutation
Niels van Nieuwenhuijzen et al. Cancer Res 2018;78:2449-2456
Kyle RA Mayo Clinic Proc 1975
Riccadi A Eur J Cancer 1991
Charge based separation of protein on gel
Low sensitivity, may miss small monoclonal proteins and light chains
• Ab’s against the heavy chains and κ and λ light chains
• Allows for identification of isotype
• Detection of small proteins missed on electrophoresis
• Unlike SPEP/UPEP, not quantitative
example:
• IgG+kappa
• IgG+lambda
• IgA+kappa
• IgA+lambda
• etc…
• 80% of myeloma cases
Jones protein
• 20% of all myeloma cases
• Renal failure more common in light chain multiple myeloma; creatinine >2 mg/dL in 1/3 of cases
protein present
• 3% of cases of multiple myeloma
• MGUS:
- Serum M protein < 3 g/dl and
- Marrow Plasmacytosis in Bone marrow < 10% (if done) and
- no disease –related symptoms
• Smoldering Myeloma:
- Serum M Protein ≥ 3 g/dl &/or
- Bence – Jones protein ≥ 500 mg/24 hr
- Clonal bone marrow plasma cells ≥ 10% -60% and
- No disease –related symptoms
• Approximately 1% per year for MGUS will progress to MM
• 10%/year in the 1st 5 years for smoldering myeloma
Blade, J et al. J Clin Oncol. 28:690,2009
Low Blood Counts
• Anemia is present in 60% at diagnosis
• May lead to anemia and infection
Decreased Kidney Function
• Occurs in over half of myeloma patients
Bone Damage
• Affects 85% of patients
• Leads to fractures
Bone Turnover
• Leads to high levels of calcium in blood (hypercalcemia)
Weakness Fatigue Infection
Weakness
Bone pain
Loss of appetite
Weight loss
About 10% to 20% of patients with newly diagnosed myeloma will not have any symptoms.
• Clonal marrow PC > 10% or biopsy proven bony or EMD plasmacytoma &
• Serum &/or urine M-protein ( unless non-secretory) &
• Evidence of end-organ damage due to disease (CRAB)
– Hypercalcemia: (> 11 g/dl)
– Renal Insufficiency ( Cr > 2 mg/dl) or CrCl < 40 ml/min
– Anemia ( < 10 g/dl or > 2 g dropped below baseline)
– Bone lesions: ( Lytic lesions)
• Amyloidosis or hyperviscosity or frequent bacterial infection
• One or more osteolytic bone lesions on PET/CT scan
• Clonal bone marrow plasma cells ≥ 60%
• > 1 focal lesions on MRI studies ≥ 5 mm
• Abn serum FLC ratio ≥ 100 (kappa) or ≤ 0.1 (lambda)
• Achieve disease response
• Reduce Active symptoms
• Prevent any additional morbidity
• Prolong the patient’s overall survival
• Minimize toxicity of therapy
• Use agents with predictable and manageable side effects
• Maximize Quality of life
• Administer medically & cost- effective therapies
• Cure?
S C T e l i g i b l e S C T i n e l i g i b l e D i a g n o s i s & R i s k S t r a ti fi c a ti o n
Tumor Burden
Consolidatio n Maintenanc e
Induction followed by continuous therapy
Paul et al. Comparative Meta-Analysis of Triplet vs.
Induction Regimens in NDMM. Cancers 2024, 16(17), 2938
Munshi et al. Blood advances 202;4:23
Munshi et al. Blood advances 202;4:23
Sustained MRD negativity was defined as having at least two MRD-negative results measured 1 year apart.
2024: MRD is approved as an endpoint in MM clinical trials!
• Most malignancies depend on angiogenesis to sustain progression.
• Tumors produce large amounts of angiogenic growth factors to induce new blood vessel production.
– Vascular Endothelial Growth Factor (VEGF).
– Basic Fibroblast Growth Factor (bFGF).
• 1999- 67 myeloma patients a significant correlation was found between disease progression and extent of bone marrow angiogenesis.
Vecca A et al.Blood; Vol.93, 1999
• Thalidomide was first marketed in West Germany in 1957 as an over-the-counter sleep aid.
• Thalidomide was withdrawn in 1961 when its birth defect effects became known.
– The damage to growing limbs seemed to be related to inhibition of blood vessel formation.
• In 1965 Olson et al. reported slowing of disease progression patients with advanced cancer treated with thalidomide.
• Thalidomide has been shown to inhibit aniogenesis induced by bFGF and VEGF in animal models.
• 1964 :Thalidomide is used to treat leprosy.
• 1979 – Thalidomide used to treat Behcet disease.
D'Amato,et al. Pro Nat Aca Sci USA,1999. Clin Pharmacol Ther. 1965;6:292-297
• 1999 –Barlogie et al, described the activity of thalidomide for refractory MM in 169 patients.
• 37% responded with a reduction of at least 25% in their Monoclonal protein.
• With a follow-up of 3.5 years, 40% were alive and 20% were disease free.
• The responses were durable, with a median duration of approximately 12 months.
Barlogie B et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood. 2001;98:492–494
• Human CD38 IgGκ monoclonal antibody
• Direct and indirect anti-myeloma activity1-5
• Depletes CD38+ immunosuppressive regulatory cells5
• Promotes T-cell expansion and activation5
1. Lammerts van Bueren J, et al. Blood. 2014;124:Abstract 3474. 2. Jansen JMH, et al. Blood. 2012;120:Abstract 2974. 3. de Weers M, al. J Immunol. 2011;186:1840-8. 4. Overdijk MB, et al. MAbs. 2015;7:311-21. 5. Krejcik J, et al. Blood. 2016. Epub ahead of print.
BCMA: a member of the TNF receptor family, expressed on the surface of all normal PCs and latestage B cells, as well as on all malignant cells in MM
Promotes the maturation and long-term survival of normal plasma cells and is essential for proliferation and survival of malignant plasma cells in MM
GPRC5D large configuration
GPRC5D is expressed marrow, owing GPRC5D mRNA in other hematologic malignancies
@Abdallah81MD
Thank you
Mayo Clinic – Rochester, MN
IMF Nurse Leadership Board, InfoLine Advisor
Myeloma and treatment
options, side effects, symptom management, & supportive care
FINDING YOUR GAIT
Know your care team & be an empowered patient
GOING THE DISTANCE Healthful and meaningful living
• Rapid and effective disease control
• Durable disease control
• Improved overall survival
• Minimize side effects
• Promote good quality of life
• Prevent disease- and treatmentrelated side effects
• Optimize symptom management
• Promote quality of life
Discuss your goals and priorities with your healthcare team.
FRONTLINE
MAINTENANCE
Velcade® (bortezomib)
Velcade® (bortezomib)
Ninlaro® (ixazomib)
Kyprolis® (carfilzomib)
RELAPSE
Ninlaro® (ixazomib)
Darzalex® (daratumumab)
Sarclisa® (Isatuximab)
Darzalex® (daratumumab) in clinical trial
Darzalex® (daratumumab)
Empliciti® (elotuzumab)
Sarclisa® (Isatuximab)
Revlimid® (lenalidomide)
Thalomid® (thalidomide)
Revlimid® (lenalidomide)
Thalomid® (thalidomide)
Revlimid® (lenalidomide)
Pomalyst® (pomalidomide)
Dexamethasone
Prednisone
Prednisolone
SoluMedrol
Dexamethasone
Prednisone
Prednisolone
SoluMedrol
Elrexfio™ (elranatamab)
Tecvayli® (teclistamab)
Talvey™ (talquetamab)
Xpovio® (Selinexor)
Doxil (liposomal doxorubicin)
PENDING
Venclexta® (venetoclax):BCL2 inhibitor for t(11;14) Blenrep™ (belantamab mafodotin)*: antibody drug conjugate
Myelosuppression,
Xpovio®: low sodium Blenrep™: eye-related
Measuring treatment response
Determining Transplant Eligibility
Insurance authorization Collecting stem cells
High Dose Chemotherapy, stem cell infusion
Supportive Care Engraftment
Duration: Approximately 2 weeks
Duration: Approximately 3-4 weeks
Location: Transplant Center
POSTTRANSPLANT
Location: HOME P H A S E 1 P H A S E 2 P H A S E 3
Location: Transplant Center
Restrengthening
Appetite recovery “Day 100” assessment
Begin maintenance therapy
Duration: Approximately 10-12 weeks
Ask for a referral to CAR Tcell center as soon as it is possible as next treatment option (ie, before relapse)
No driving for 8 weeks
“One & Done” with continued monitoring
T-Cell Collection
Manufacturing takes ≈ 4 to 6
Bridgingweekstherapy may be needed
• Away from home
• Often some hospital stay
• Care Partner needed
• Side effect management
• CRS, ICANS
• Low blood counts
• Fatigue and fever
• Some patients need ongoing transfusion support
• Different bispecific antibodies have differences in efficacy, side effects
– Available after 4 prior lines of therapy (or clinical trial)
– About 7 in 10 patients respond
– Off-the-shelf treatment; no waiting for engineering cells
– CRS and neurotoxicity
– Risk of infection
• BCMA target: greater potential for infection
– Tecvayli® (teclistamab)
– Elrexfio™ (elranatamab)
• GPRC5D target: potential for skin and nail side effects, GI issues of taste change, anorexia and weight loss
– Talvey™ (talquetamab)
Steroids enhance the effectiveness of other myeloma therapies
Do not stop or alter your dose of steroids without discussing it with your provider
Managing Steroid Side Effects
• Consistent schedule (AM vs. PM)
• Take with food
• Stomach discomfort: Over-the-counter or prescription medications
• Medications to prevent shingles, thrush, or other infections
• Irritability, mood swings, depression
• Difficulty sleeping (insomnia), fatigue
• Blurred vision, cataracts
• Flushing/sweating
• Increased risk of infections, heart disease
• Muscle weakness, cramping
• Increased blood pressure, water retention
• Stomach bloating, hiccups, heartburn, ulcers, or gas
• Weight gain, hair thinning/loss, skin rashes
• Increased blood sugar levels, diabetes
cause:
• Calcium elevation
• Renal dysfunction
• Low blood counts
• Infection Risk
• Blood clots
• Bone pain
• Neuropathy
• Fatigue
Your team may be able to help, but only if they know how you feel.
cause:
• GI symptoms
• Renal dysfunction
• Low blood counts
• Infection Risk
• Blood clots
• Neuropathy
• Fatigue
Infection remains the leading cause of death in patients with multiple myeloma. Several factors account for this infection risk, including the overall state of immunosuppression from multiple myeloma, treatment, age, and comorbidities (e.g., renal failure and frailty).
IMWG Consensus guidelines and recommendations for infection prevention in multiple myeloma; Lancet Haematol.2022;9(2):143–161.
Good personal hygiene (skin, oral)
Environmental control (avoid crowds and sick people; use a high-quality mask when close contact is unavoidable)
Report fever of more than 100.4°F, shaking chills even without fever, dizziness, shortness of breath, low blood pressure to HCP as directed.
As recommended by your healthcare team:
Flu, COVID, RSV & and pneumococcal vaccinations; avoid live vaccines
Preventative and/or supportive medications (next slide)
Type of Infection Risk
Herpes virus reactivation (HSV/VZV); CMV reactivation
Bacteremia, pneumonia, and urinary tract infection
PJP (P jirovecii pneumonia)
Acyclovir prophylaxis
Consider prophylaxis with levofloxacin
Consider prophylaxis with trimethoprim-sulfamethoxazole
Fungal infections (aspergillus)
Consider prophylaxis with fluconazole IgG < 400 mg/dL or recurrent infections
< 500 cells/μL
GCSF 2 or 3 times/wk (or as frequently as needed) to maintain ANC > 1000 cells/μL and maintain treatment dose intensity
Antiviral therapy if exposed or positive for covid per institution recommendations and current FDA guidelines
Some people receiving BCMA-targeting therapies have experienced infections that are less common like CMV, PJP and fungal infections
Sources of pain include bone disease, neuropathy and medical procedures
• Management
– Prevent pain when possible
• Bone strengtheners to decrease fracture risk
• Antiviral to prevent shingles
• Sedation before procedures
– Interventions depend on source of pain
Tell your healthcare provider about any new bone or chronic pain that is not adequately controlled
• May include medications, activity, surgical intervention, radiation therapy, etc
• Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture, etc)
• Scrambler therapy for neuropathy
Peripheral neuropathy happens when there is damage to nerves in the extremities (hands, feet, limbs). Damage can be the result of myeloma, treatment or unrelated conditions (i.e. diabetes).
Symptoms:
• Numbness
• Tingling
• Prickling sensations
• Sensitivity to touch
• Burning and/or cold sensation
• Muscle weakness
Prevention / management:
• Bortezomib once-weekly or subcutaneous administration
• Massage area with cocoa butter regularly
• Neuroprotective Supplements:
– B-complex vitamins (B1, B6, B12)
– Green tea
• Safe environment: rugs, furnishings, shoes
If neuropathy worsens, your provider may:
• Adjust your treatment plan
• Prescribe oral or topical pain medication
• Suggest physical therapy
Report symptoms of peripheral neuropathy early to your health care provider; nerve damage from neuropathy can be permanent if unaddressed
B, et al. CJON. 2017;21(5)suppl:19-36. Tariman, et al. CJON.2008;12(3)suppl:29-36. Zhao T, et al. Molecules. 2022;27(12):3909.
• Risk Factors
– Active multiple myeloma (light chains, high calcium)
– Other medical issues (ex: Diabetes, dehydration, infection)
– Medications (MM treatment, antibiotics, contrast dye)
• Prevention
– Stay hydrated – drink water
– Avoid certain medications when possible (i.e., NSAIDs), dose adjust as needed
• Treatment
– Treatment for myeloma
– Hydration
– Dialysis
Many myeloma patients will experience kidney issues at some point; protecting your kidney function early and over time is important
Diarrhea may be caused by medications and supplements
– Laxatives, antacids with magnesium
– Antibiotics, antidepressants, other (check with provider, pharmacist)
– Supplements: milk thistle, aloe, cayenne, saw palmetto, ginseng
Management:
Avoid caffeinated, carbonated, or heavily sugared beverages
Take anti-diarrheal medication if recommended
Bile Acid Sequestrants can reduce bile acid diarrhea
(Ex: cholestyramine, Colestid® (colestipol), Welchol® (colesevelam)
Constipation may be caused by medications and supplements
– Opioid pain relievers, antidepressants, heart or blood pressure medications (check with provider, pharmacist)
– Supplements: Calcium, Iron, vitamin D (rarely),
vitamin B-12 deficiency
Increase fiber
• Fruits, vegetables, high fiber whole grain foods
• Fiber binding agents – Metamucil®, Citrucel®, Benefiber®
Discuss GI issues with health care providers to identify causes and make adjustments to medications and supplements
Fluid intake can help with both diarrhea and constipation and helps kidney function
Weight Management
Anorexia (difficulty eating) Weight loss; Steroids Weight gain
– Monitor weight for significant loss or gain
– Adjust diet (reduce calories or add supplements )
Taste Changes Glossitis and Thrush
Dry Mouth
Dexamethasone oral solutions “swish and spit” have been tried but with no proven benefit yet. Sour citrus or candies before meals are also recommended.
EARLY initiation of nystatin or Mycelex is key to manage symptoms.
OTC dry mouth rinse, gel, spray are recommended. Avoid hot beverages. Preventative dental care and cleaning
Dysphagia (difficulty swallowing)
Dietary modifications with small bites, eating upright, and sips with food can help manage symptoms.
• Weight loss and anorexia are associated with taste changes. Working with a Nutritionist and dietary changes may be recommended. Appetite stimulant with Marinol, if indicated, can also be utilized.
• Learn more and find support with your care team.
CRS is a common but often a mild & manageable side effect
CAR = chimeric antigen receptor; CRS = cytokine release syndrome. Oluwole OO, Davila ML. J Leukoc Biol. 2016;100:1265-1272. June CH, et al. Science. 2018;359:1361-1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45-55. Shimabukuro-Vornhagen, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.
Possible side effects to some treatments and supportive care medications
Body Rash:
• Prevent dry skin; apply lotion
– Ammonium lactate 12% lotion
• Steroids:
– Topical for grades 1-2,
– Systemic and topical for Grade 3 and dose hold
• Antihistamines, as needed
Nail Changes:
.
• Keep your nails short and clean. Watch for “catching and tearing”
• Apply a heavy moisturizer like Vaseline or salve. Wear cotton hand coverings to bed
• A nail hardener may help with thinning
• Tell the team if you have signs of a fungal infection, like thickened or discolored nails
Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.
Financial burden comes from
• Medical costs
– Premiums
– Co-payments
– Travel expenses
– Medical supplies
• Prescription costs
• Loss of income
– Time off work or loss of employment
– Caregiver time off work
• Funding and assistance may be available
– Federal programs, IRA & Medicare “Extra Help”
– Pharmaceutical support
– Non-profit organizations (TriageCancer.org)
– Websites:
• Medicare.gov
• SSA.gov
• LLS.org
• Rxassist.org
• NeedyMeds.com
• HealthWellFoundation.org
• Company-specific website
Be an empowered patient; engage in your care
Know the members of your care team - Understand their different roles
Myeloma specialist & General Heme/Onc
Primary care: for health screening, general check ups, vaccinations
Sub-specialists: specialty needs
Keep a contact list of your providers Communicate with your team
• Prepare for medical visits
• Provide symptom updates
• Know the plan
• Include a Care Partner
Identify that a decision is needed: The HCP informs the patient that a decision is to be made and that the patient's opinion is important (Choice talk).
Understand the options:
The HCP explains the evidence-based options and their pros and cons. The patient expresses their preferences, and the HCP supports the patient in decision-making (Option talk).
Come to a decision:
The HCP and patient discuss the patient's wish to take part in the decision making and incorporate the patient's values and preferences into the decision (Decision talk).
Follow-up: Review and evaluate the decision, adjust as needed
Website: http://myeloma.org
98.8%
Fatigue is the most commonly reported symptom.
Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression
>35% of patients
≈25% of patients
Often, people do not share these symptoms with their provider. Talk to your provider about symptoms that are not well controlled or if you have thoughts of self harm. Help is available.
If you want to go fast, go alone; if you want to go far, go together
• Care partners may help in many ways including medical appointments, managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions
• Care partners can be a spouse, close relative, a network of people (family, friends, neighbors,
• Caring for the Care Partner
– Recognize that caregiving is difficult/stressful
– Encourage care partners to maintain their health, interests, and friendships
– The IMF has information and resources to help care partners
• Multiple studies demonstrate that strong social ties are associated with
– Increased longevity including people with cancer
– Improved adherence to medical treatment leading to improved health outcomes
– Lower risk of developing cardiovascular diseases
– Increased sense of purpose and life satisfaction
– Reduced stress and anxiety
– Improved mood and happiness
– Enhanced resilience
GOING THE DISTANCE
• Strategies for enhancing social connection
– Deepen existing relationships with family, friends, and loved ones
– Build new relationships by participating in a support group, joining clubs or organizations, or volunteering
Tip: Start with small steps outside your comfort zone. Call a loved one you haven’t spoken to in a while. Invite a person you’d like to know better for lunch, coffee, or a walk.
Martino J, et al. Am J of Lifestyle Med. 2015;11(6):466-475.
Yang YC, et al. Proc Natl Acad Sci U S A. 2016;113(3):578-583.
Pinquart M and Duberstein PR. Crit Rev Oncol Hematol. 2010; 75(2):122–137.
Hetherington C. Healthnews. https://healthnews.com/longevity/healthspan/social-connection-andlongevity/#:~:text=Research%20consistently%20demonstrates %20that%20people,of%20fulfillment%20in%20your%20life. Accessed Feb 1 2024.
Have a Primary Care Doctor
Have Recommended Health Screenings
• Blood pressure
• Cholesterol
• Cardiovascular disease
• Dermatology (Skin)
• Diabetes
• Colonoscopy
• Vision
• Hearing
• Dental checkups & cleaning
• Women specific: mammography, pap smear
• Men specific: prostate
Maintain a healthy weight
• Good nutrition
• Activity or exercise
• Sufficient sleep
An ounce of prevention is worth a pound of cure.
Benjamin Franklin
Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56.
Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.
Please take a moment to reflect and respond to the program evaluation.
Questions 7 & 8 can be worked on after each presentation. We greatly appreciate your time and feedback!
Thank you to our sponsors!
Attaya Suvannasankha, MD
Indiana University School of Medicine
Indianapolis, IN
INDIANA UNIVERSITY SCHOOL OF MEDICINE
• How do we read newly diagnosed multiple myeloma today?
• How do we choose the right therapy?
• what is the role for stem cell transplant?
• How do we treat transplant eligible patients?
• How do we treat transplant ineligible patients?
• What is to come?
• Conclusions
INDIANA UNIVERSITY SCHOOL OF MEDICINE
A 67 year-old man was seen by her primary care physician for new onset low back pain. He was found to be anemic with a high calcium level in her blood and worsening kidney function (Cr 2.1 mg/dl)
Her primary care physician checked an SPEP, which revealed M-spike of 1.2 gm/dl, Ig kappa by immunofixation. Serum kappa light chain 423 mg/L., lambda 12.3 mg/L.
A follow-up PET scan showed multiple bone lesions, and a bone marrow biopsy showed 60% plasma cells.
FISH: monosomy 13. B2M 3.8, LDH 325 mg/dl
She is referred to see Dr. MM
What factors does Dr. MM use to decide what to treat her with?
How should Dr. MM monitor her response to treatment?
What other issues are important for Dr. MM to consider?
Myeloma is a heterogeneous disease
Time (years)
Understanding that each patient's disease is different helps us define the best possible individualized approach to care
Staging tells us how to approach each patient
INDIANA UNIVERSITY SCHOOL OF MEDICINE
Your Overall Health and Characteristics of Your Myeloma
• Age and general health
• Test results: stage, cytogenetics
• Symptoms
• Other medical conditions
Your Preferences and Personal Goals
• Eliminate vs control disease
• Willingness to tolerate side effects
• Symptom relief
• Personal lifestyle/situation
No one treatment plan is right for everyone.
If you are comfortable with it, consider a clinical trial if available.
If you are not comfortable, consider a 2nd opinion
Induction
Induction followed by continuous therapy “Consolidation” Maintenance
GOAL
Tumor burden
Disease control and reversal of symptoms and signs
Maximize disease control to provide durable disease control while optimizing QoL
Most patients will be given a combination of drugs to control the disease quickly
We don’t “save the best for later” because early use of highly effective drugs have a long-term effect on survival
We seek a DEEP and DURABLE response
We use a combination of the following for 1st line therapy:
– Immunomodulatory drug (IMiD) = Lenalidomide (revlimid)
– Proteosome inhibitor (PI) = bortezomib (velcade) or carfilzomib (kyprolis)
– CD38-directed monoclonal antibody = daratumumab (darzalex) or isatuximab (sarclisa)
– Corticosteroid
We decide whether someone should be considered for transplant
Response Type
Stringent complete response (sCR)
Complete response (CR)
Very good partial response (VGPR)
Partial response (PR)
Minimal response (MR):
None (blood/urine)
None (blood/urine)
Greater than 90% reduction (blood)
Greater than 50% reduction in blood +
Greater than 90% reduction in urine
25%-49% reduction in blood and reduction of 50%89% in urine
No abnormal plasma cells
Less than 5%
NA
No free light chains
Disappearance of soft tissue plasmacytomas*
NA
NA
Greater 50% reduction in the size of soft tissue plasmacytomas
NA
Stable disease (SD) Does not meet criteria for response or progressive disease
Progressive disease (PD)
Greater than 25% increase (blood or urine)
*Soft tissue plasmacytomas: collection of plasma cells outside the bone
Greater than 10%
25%-49% reduction in the size of soft tissue plasmacytomas and no increase in size/ number of bone lesions
Other changes: bone lesions, soft tissue plasmacytomas, high calcium levels
Small amounts of myeloma cells despite CR (as measured by standard tests)
Patients who are MRD negative may have better outcomes
More-sensitive tests/newer technologies to detect and monitor MRD are now available
Flow cytometry
Molecular tests
Polymerase chain reaction (PCR)
Sequenta ClonoSIGHT*: novel, highly sensitive test
New response types incorporating use of new technologies
Immunophenotypic CR
At diagnosis
Partial response –50% reduction in M protein
Near complete remission –immunofixation positive only
Complete remission –immunofixation negative
Nonquantitative ASO-PCR
Molecular CR Talk to your doctor about types of tests available in your area.
*The Multiple Myeloma Research Foundation is using the Sequenta ClonoSIGHT test in the CoMMpass research study.
Newly diagnosed multiple myeloma (NDMM): Transplant eligible
Initial therapy regimens for multiple myeloma
S0777, IFM2009
Triplet Regimens Quadruplet Regimens
Velcade-Len-Dex (VRd)
Carfilzomib-Len-Dex (KRd)
Velcade-Thal-Dex (VTd)
Velcade-MEL-Dex (VMP)
Daratumumab-Len-Dex (Dara-Rd)
CyBorD
Dara-RVd
Dara-KRd
Dara-VTd
Dara-VMP
Isa-RVd
Isa-KRd
PERSEUS
GMMG-HD7, IMROZ
IsKia, CONCEPT
Quad-induction is now considered SOC for transplant eligible patients, though triplet may be adequate for less fit patients
GRIFFIN was the first quad-based trial design in the US and the first to investigate the addition of daratumumab to a lenalidomide-based triplet
At all time points, response rates were higher for D-RVd; rates of ≥CR improved over time and were deepest at the end of study maintenance
D-RVd/DR was associated with a clinically meaningful 55% reduction in risk of progression or death. The PFS curves separated beyond 1 year of maintenance
Lancet Heme, 2023
Primary Endpoint: PFS INDUCTION
4 – 28-day cycles
Dara-RVd
Dara SQ1800 mg qw C1-2, q2w C3-4 +V
Len 25 mg/d d1-21, Dex 40 mg d1-4, 912
Bortezomib 1.3 mg/m2 d1,4,8,11
Len 25 mg d1-21, Dex 40 mg d1-4, 9-12
Dara SQ 1800 mg q2wk + V Len 25 mg/d d1-21, Dex 40 mg d1-4, 912
Bortezomib 1.3 mg/m2 d1,4,8,11 Len 25 mg d1-21, Dex 40 mg d1-4, 9-12 CONSOLIDATION
2 – 28-day cycles R Lenalidomide 10 mg Continuous d1-28 MAINTENANCE
*Defined as del17p, t(4;14), t(14;16)
progression
*After 24 months of DR maintenance, discontinue D for patients with > CR and MRD negativity for at least 12 months –Restart dara if loss of CR or MRD- without PD
PERSEUS was a multi-center trial based in Europe that investigated the D-RVd quad in a randomized phase 3 trial powered for PFS
48-month PFS
At a median follow-up of 47.5 months, D-RVd was associated with a 58% reduction in the risk of
Primary endpoint 1: MRD rate post-induction
Endpoints sCR post-consolidation
Drug exposure during induction
Randomization 1: Rate of MRD negativity post-induction
Randomization 2: PFS after 2nd randomization
Mobilization G-CSF +/- plerixafor CAD (Cyclophosphamide, doxorubicin, dexamethasone)
Tandem allowed?
Patients treated with tandem No Tandem for patients not in > CR Not reported
Response after consolidation
Primary Endpoint: Rate of MRD- post-consolidation
INDUCTION
4 – 28-day cycles
KRd as below
vs KRd
(N = 302)]
Carfilzomib 20/56 d1,8,15
CONSOLIDATION
4 – 28-day cycles
Isa 10 mg/kg q2w KRD as below
Carfilzomib 20/56 d1,8,15 Len 25 mg d1-21, Dex 40 mg qweek
*Defined as del17p, t(4;14), t(14;16) per IMWG, + 1q21 per R2-ISS
Quadruplet induction + transplant +/- consolidation is SOC for most 3- vs 4-drug question is answered and it is time to investigate more novel approaches
Autologous stem cell transplantation: Schema
Stem cell collection
Induction therapy
High dose chemotherapy: Melphalan
200 mg/m2
Autologous stem cell rescue Maintenance therapy
Purpose: Consolidate/deepen remission
Prolong remission
Perrot A. ASH 2020. Abstract 143.
Median follow up 89.8 months
8y-OS 60.2% (RVD alone, arm A) 8y-OS 62.2% (Transplantation, arm B)
HR (95CI) 1.03 [0.8;1.32]
More than 60% of the patients in the two arms are alive after 8 years of follow-up
Study design initially paralleled IFM 2009, but following CALGB 100104, maintenance was changed to indefinite Len or until intolerance or progression
Lack of OS difference maybe related to availability of novel therapeutics @ relapse
CIBMTR Analysis of Trends in MM-SCT1
1995-1999; 200-2004; 2005-2009
More people are being referred to SCT
But still not same proportion of older patients as younger patients
However, age alone does not appear to predict poor outcomes from SCT
No difference in death, TRM, PFS and OS for patients < or > 602
Patients > 70 undergoing SCT have similar responses and OS compared with younger patients3
Patients even up to age 80 can undergo SCT safely4
2.
3.
4.
Am I a candidate for high-dose chemotherapy and stem cell transplantation?
What are the pros and cons of stem cell transplantation in my case?
When is the best time for me to undergo transplantation?
Does your center do stem cell transplants? How many transplants has your center performed in multiple myeloma in the last year? Is procedure performed as an inpatient or outpatient?
How long will I be in the hospital?
What is the recovery period?
What kind of changes in my lifestyle will I need to make?
Patients younger than 65 had better outcomes with triplet RVd. Older patients might do better.
PRIMARY ENDPOINTS
PFS (induction)
OS (maintenance)
Dara-Rd vs Rd [P3 (N = 737)]
Primary Endpoint: Progression Free Survival
Dara 16 mg/kg qwk C1-2, q2w C3-6, q4w C7+
Len 25 mg/d d1-21, Dex 40 mg qwk* Rd
Len 25 mg/d d1-21, Dex 40 mg qwk*
*Reduced to 20 mg/wk if > 75 yrs of age or BMI < 18.5
28-day cycles until disease progression or intolerability
Daratumumab in the frontline setting improves outcomes in patients unfit for autoHSCT
Progression-Free Survival
At 5-year follow-up, mPFS not reached in the DRd group vs 34.4 months in Rd group; HR, 0.53; P <.0001
Median OS not reached in either group; HR, 0.68; P = .0013)
In tiNDMM, DRd is associated with unprecedented depth of response and PFS. DRd is considered the SOC for this patient population
International, randomized, open-label phase III trial
Stratified by age (<70 vs ≥70 yr), R-ISS stage (I or II vs III vs not classified), and China vs nonChina
Patients 18 to ≤80 yr of age with symptomatic NDMM not considered for transplant due to older age or comorbidities (N = 446)
Induction (4 x 6-wk cycles)
Continuous Treatment (4-wk cycles) 3:2
Isatuximab* + VRd† (n = 265) VRd† (n = 181)
Isatuximab‡ + Rd§ (n = 265) Rd§ (n = 181)
*Isa IV (C1 only) 10 mg/kg Q1W; Isa IV (C2-4) 10 mg/kg Q2W. †V: SC 1.3 mg/m2 on D1,4,8,11,22,25,29,32; R: PO 25 mg on D1-14 and 22-35; d: IV/PO 20 mg on D1,2,4,5,8,9,11,12,15,22,23,25,26,29,30,32,33.
‡Isa IV (C5-17) 10 mg/kg Q2W; Isa IV (C18+) 10 mg/kg monthly. §R: PO 25 mg on D1-21; d: IV/PO 20 mg on Q1W.
Primary endpoints: PFS Secondary endpoints: CR rate, MRD− CR (NGS 10-5) rate, ≥
Facon. ASCO 2024. Abstr 7500. Facon. NEJM. 2024;[Epub].
Until PD, unacceptable toxicity, or patient withdrawal
Crossover from Rd to Isa-Rd allowed upon progression
OS data immature at 5-yr analysis
60-mo OS rate: 72.3% vs 66.3% for Isa-VRd vs VRd, respectively; HR: 0.78 (99.97% CI: 0.41-1.48)
QoL similar between 2 arms
Phase 3 study of DARA-VRd versus VRd in transplant-ineligible NDMM
Induction/Consolidation
V: 1.3 mg/m2 SC Days 1, 4, 8, 11
Key eligibility criteria:
• Transplantineligible NDMM or deferred
• CrCl <40 mL/min
• ECOG PS ≤2
R: 25 mg PO Days 1-14
d: 20 mg PO/IV Days 1,2,4,5,8,9,11,12
Maintenance
DARA SC-VRd
DARA: 1,800 mg SC
Cycles 1-2 QW
Cycles 3-8 Q3W
VRd: Same as control
R: 25 mg PO Days 1-21 d: 40 mg PO Days 1,8,15,22
Primary endpoint:
• Overall MRD negativity rate at 10-5
Secondary endpoints:
• PFS
• Durable MRD negativity at 1-yr
• Response
• PFS2
• OS
8 Cycles of 21 days
Quadruplet therapy will likely become the new SOC for both transplant-eligible and ineligible patients. Frailty remains a key concern for transplant ineligible patients
Deep remission is key: MRD negativity
We may achieve a “functional cure” in many patients
Stem cell transplantation: Offers best chance for long-term remission for eligible patients based on current data
Research questions: Given the availability of the novel agents, what is the role of transplant?
Regional Community Workshop
October 19th,
Please take a moment to reflect and respond to the program evaluation.
Questions 7 & 8 can be worked on after each presentation.
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• May 2013 following double pneumonia
• 67% myeloma cells in my bone marrow
• 4:13 Translocation
• Began four rounds of RVD (Revlimid, Velcade, Dexamethasone) the Summer of 2013.
• Learning about the process – orientation, big black book, preparing our home
• Lou – Medical Leave from Teaching David – FMLA Leave from Teaching
• Stem Cell Transplant – November 2013
• Lack of Appetite – Peaches and Lima Beans
• Fatigue/Sleeping
• Intestinal Issues, Nausea, Neuropathy
• Low ANC (Absolute Neutrophil Count)
• Admitted to hospital for fever (e coli infection)
(Remission lasted almost three years from Stem Cell Transplant)
• Revlimid, Pomalyst, Kyprolis, Darzalex
• Clinical Trials: CAR-T - Abecma (2019)
Iberdomide (2021)
Teclistamab (2022)
Allo CAR-T (2023)
• IMF Support Group which provides knowledgeable speakers, conferences, and resources. There are support groups around the country led by wonderful leaders.
• IMF provides information about myeloma and has a website myeloma.org that provides booklets and videos, and a Helpline (800/452-CURE).
• Healthtree (healthtree.org) provides learning videos, information regarding clinical trials, and a coaching program.
• Clinical Trials:
KU Cancer Center Website lists those available through KU
Clinicaltrials.org – government website
SparkCures.com – provides personalized list of clinical trials and a person who will help you find a clinical trial
David and Lou with daughters Heather and Katie and granddaughters Clara and Lily – Fall of 2013.
Overland Park Elementary Staff in “Team Lou Can Do” tees. My last day prior to SCT.
Daughter Heather with granddaughters Lily and Clara PePaw (David) with youngest granddaughter Isla Rose Lou with sister Sherry and brother Dan
Daughter Katie with husband Kyle and grandchildren Charlotte, Isla Rose, and Ben
London
Rome
Paris
Florence
• Be involved in decision making concerning your treatment.
Practice saying, “What’s next?”
• Sometimes you can focus so much on your disease you forget to live.
• Myeloma is just a small part of who you are.
• We can do hard things. We do it every day.
Indianapolis, IN
INDIANA UNIVERSITY SCHOOL OF MEDICINE
• Less intense and longer-term therapy with goal of prolonged disease control (PFS) and survival (OS)
• Ideal maintenance regimen will obtain:
• Deep, prolonged remission
• Easy drug administration
• Minimal toxicity
Indefinite lenalidomide maintenance is considered standard of care in all ”standard risk” patients
•Average follow-up = 6.6 years
•PFS: 52.8 months (lenalidomide) vs 23.5 months (placebo)
•PFS2: 73.3 months (lenalidomide) vs 56.7 months (placebo)
•Average overall survival (OS): NR vs 86 months
•All responding patients benefited from maintenance therapy
•29% patients discontinued lenalidomide maintenance
•Second primary malignancy (SPM) occurred more frequently (6.1%) with lenalidomide maintenance than placebo (2.8%)
•Average duration of lenalidomide therapy = 28 cycles (range 1-96)
•There is an ongoing PFS benefit associated with continuing lenalidomide maintenance > 4-5 years in the overall patient population
•Even in those patients that are MRD negative, there is evidence of benefit for continuing maintenance for at least 3 years
•In MRD+ patients, continue lenalidomide maintenance until progression
Ultimate question: Which patients need to continue indefinite maintenance vs stopping at some earlier time point like 2 or 3 years
Sonneveld P, et al. JCO 2012;30:2946.
Moreau P, et al. Lancet Oncol 2021;22:1378.
<65 years, NDMM [rP2 (N = 396)]
CCd (n = 138)
CFZ 20/36 mg/m2
Cytoxan 300 mg/m2
(d1,8,15)
Dex 40 mg qwk
INDUCTION (4 cycles) R1
KRd (n = 132)
CFZ 20/36
(d1,2,8,9,15,16)
Len 25 mg d1–d21
Dex 40 qwk
KRd (n = 126)
CFZ 20/36 mg/m2
(d1,2,8,9,15,16)
Len 25 mg d1–d21
CONSOLIDATION × 4
CCd
CFZ 20/36 mg/m2
Cytoxan 300 mg/m2 (d1,8,15)
Dex 40 mg qweek
KRd
CFZ 20/36 mg/m2
(d1,2,8,9,15,16)
Len 25 mg d1–d21
Dex 40 mg qweek
Len 10 mg d1–d21 Until progression
Dex 40 mg qweek KR
KRd
CFZ 20/36 mg/m2
(d1,2,8,9,15,16)
Len 25 mg d1–d21
Dex 40 mg qweek
CFZ 20/36 mg/m2
(d1, 2, 15, 16)*
Len 10 mg d1–d21 Until progression
*Up to 2 years
Primary endpoint: Rate of ≥ VGPR
Secondary endpoints: Rate of sCR and MRD–, incidence of G3/4 AE, survival** **Three induction/consolidation and 2 maintenance arms
KRd + Auto significantly prolonged PFS vs KRd12 in standard- and high-risk patients.
KR significantly prolonged PFS from the start of maintenance vs R in all patients
Some patients (high risk features) benefit from 2-drug therapy, but which 2 drugs?
•Lenalidomide + proteosome inhibitors
• Emory dataset, FORTE
•Daratumumab
• CASSIOPEIA – Single agent daratumumab > placebo (PFS)
•Lenalidomide + daratumumab
• GRIFFIN, PERSEUS, AURIGA, S1803 (DRAMMATIC)
• Addition of daratumumab deepens response (CR and MRD negativity
• Still so much to learn and we need more and longer term data
Inclusion
aCD38 mAb naïve
Induction/autoHSCT
< 12 months of transplant
MRD+ at screening
Primary endpoint - MRD conversion rate after 12 month
Inclusion
Induction/autoHSCT
<
•The choice of maintenance therapy should be risk adapted
• Patients with standard-risk disease should be treated with single-agent, dose-reduced lenalidomide
• Patients with high-risk features including (but not limited to) EMD and highrisk cytogenetics should be considered for lenalidomide-based doublet maintenance
• Choice of doublet maintenance partner will be patient specific
•Data support that maintenance should be given indefinitely; however, we are likely overtreating some patients
•SWOG S1803 (DRAMMATIC) and others will help define this space in the future
Al-Ola Abdallah, MD
University Of Kansas Medical Center
Kansas City, KS
Al-Ola A. Abdallah, MD
Associate Professor of Medicine
Director, Plasma Cell Disorder Clinic
Division of Hematologic Malignancies and Cellular Therapeutics
Department of Internal Medicine
The University of Kansas Cancer Center
October 19,2024
I have NO financial relationships to disclose
• “ treatment in multiple myeloma.”
Holland JR, Hosley H, Scharlau C, Carbone
PP, Frei E 3rd, Brindley CO, Hall TC, Shnider
BI, Gold GL, Lasagna L, Owens AH Jr, Miller
SP
• Randomized 83 patients with treated or untreated multiple myeloma to receive urethane cherry- and cola flavoured syrup.
• No difference was seen in objective improvement or in survival in the two treatment groups. In fact, the urethanetreated patients died earlier.
• Pattern of relapse:
1. Insidious form: Increase in myeloma markers in serum or urine without other clinical manifestation 18%
2. Classical form: Progressive increase in myeloma markers, classic myeloma symptoms and new osteolytic lesions 66%
3. Plasmacytoma form: Extramedullary disease 14%
4. Plasma cell leukemia: 2%
Disease Related
Therapy Related
Patient Related
• Place of relapse
• Cytogenetics
• Disease burden
• Previous Therapies
• Prior treatmentrelated AE
• Regimen-related toxicity
• Depth and duration of previous response
• Fitness
• Comorbidities
• Organ Function
• Preferences
• Social Factors
Immunomodulatory Drugs (IMIDS)
Thalidomide (Thalomid)
Lenalidomide (Revlimid)
Pomalidomide (Pomalyst)
Proteosome Inhibitors (PIs)
Bortezomib (Velcade)
Carfilzomib (Kyprolis)
Ixazomib (Ninlaro)
Corticosteroids
Dexamethasone
MoA
Daratumumab
Isatuximab
Elotuzumab
Newer agents
Selinexor
Belantamab
BCMA/CAR-T
Idea-Cel
Cita-Cel
Teclstimab
Elrantamab ±
Talquetamab
• No patient had CR or SD as best response • sCR rates deepened over time – 67% at median 1-yr follow-up – 83% at median 2-yr follow-up – 92% pts achieved MRD negativity
• Median time to first response: 1 mo (0.9-10.7)
• Median time to best response: 2.6 mo (0.9-17.8)
• Median time to ≥CR: 2.9 mo (0.9-17.8)
• Median DoR: NE (range: 21.8-NE)
• 60.5% : progression-free at 2 yr
Median onset and median duration of CRS 2/2 days
Lesokhin AM. et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023 Sep;29(9):22592267. doi: 10.1038/s41591-023-02528-9. Epub 2023 Aug 15. PMID: 37582952; PMCID: PMC10504075.
T-cell activation Cytokine release Perforin/granzym
• Multicenter, open-label phase I/II trial
Adults with measurable MM
Phase I: progression on or intolerance to all established therapies; ECOG PS 01
Phase II: ≥3 prior lines of therapy that included a PI, an IMiD, and an anti-CD38 antibody; ECOG PS 0–2
• Primary endpoint (phase II): ORR
Talquetamab 0.4 mg/kg SC QW* (n = 143)
Talquetamab 0.8 mg/kg SC Q2W* (n = 145)
Prior T-Cell Redirection Group: Talquetamab
Either 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W (n = 51)
• Secondary endpoints (phase II): DoR, ≥ VGPR rate, ≥ CR, sCR rate, TTR, PFS, OS, MRD, safety
Chari A et al. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022 Dec 15;387(24):2232-2244. doi: 10.1056/NEJMoa2204591. Epub 2022 Dec 10. PMID: 36507686.
*Previous anti-BCMA therapy allowed; T-cell redirection therapy naive.
Chari. ASH 2022. Abstr 157. NCT03399799. NCT04634552.
Exposure
n
Refractory status, n (%)
PI
IMiD
Anti-CD38 mAb
Belantamab
• Fc receptor- homolog 5 (FcRH5)
- Expressed on myeloma cells with near 100% prevalence
- Expressed on myeloma and plasma
• Cevostamab:
- Humanized IgG- based - cell-engaging bispecific Ab
- Targets FcRH5 on myeloma and CD3 on T-cells
• Daratumumab/Isatuximab based therapy in early relapse is an optimal choice if pts can not receive CAR-T
• Choose wisely in relapsed myeloma based on the prior lines of therapy (PI/IMiD refractory)
• Ide-Cel /Cita-Cel (FDA approved) treatment of triple Class-Refractory Myeloma
• BCMA BiTE available! Challenge in RW is Infections, infections and infections!
• New class of RRMM now is evolving post BCMA and GPRC5D refractory disease!
• Need more trials for this new class
Remember some of the important principles of clinical trials:
• The drive of research has brought us to where we are
• No one is expected to be a “guinea pig” with no potential benefit to them
• Research is under very tight supervision and standards
• Open, clear communication between the physician and the patient is fundamental
• Every patient is unique and must be viewed that way
• Benefits of trials are numerous and include:
• Early access to “new” therapy
• Delay use of standard therapy
• Contribution to myeloma world – present and future
• Financial access to certain agents
• Must be balanced with potential risks
• “Toxicity” of side effects
• Possibility of lack of efficacy
ANIMAL STUDIES: Examine safety and potential for efficacy
FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS
• Determine metabolism and PK/PD actions, MTD, and DLT
• Identify AEs
• Gain early evidence of efficacy, studied in many conditions; typically, 20 to 80 patients; everyone gets agent
EVALUATION OF EFFECTIVENESS IN A CERTAIN TUMOR TYPE
• Determine short-term AEs and risks; closely monitored
• Includes up to 100 patients, typically
GATHER ADDITIONAL EFFECTIVENESS AND SAFETY INFORMATION
COMPARED TO STANDARD OF CARE
• Placebo may be involved if no standard of care exists; hundreds to several thousand patients
• Often multiple institutions; single or double blind; sometimes open label
AGENTS IN NEW POPULATIONS OR NEW DOSE FORMS
Patients may:
• Be unaware of clinical trials
• Lack access to trials
• Fear, distrust, or be suspicious of research
• Have practical or personal obstacles
• Face insurance or cost problems
• Be unwilling to go against their physicians’ wishes
• Not have physicians who offer them trials
• Have a disconnect with their healthcare team
There has been a lack of diverse representation in clinical trials in myeloma.
• In the U.S., approximately 20% of all myeloma patients are of African descent, but only 5%–8% of patients in myeloma clinical trials are of African descent.
This is significant for the following reasons:
• All patients of all races and ethnicities should be able to benefit from clinical trials.
• Diverse patient representation in clinical trials is required to ensure that the outcomes are applicable to all patients.
Reasons for underrepresentation in clinical trials are complex and include:
• systemic racism, accessibility of clinical trials, sensitivity to diversity by medical professionals
• misconduct in medicine in the past, the lack of trust in the system, and more.
https://clinicaltrials.gov/
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November 12th, 2024
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November 16th, 2024 – Phoenix RCW – DoubleTree
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Thank you for attending today’s program!
October 19th, 2024 International Myeloma Foundation’s
Regional Community Workshop –