Myeloma Round Table: Disease Progression in Relapsed/Refractory Disease - New York Part 2
Posted: Jul 12, 2022
Perhaps the best evidence of the progress in myeloma treatment is much better outcomes for relapsed/refractory patients are increasing because they have more options targeting different therapeutic approaches than ever. Until cures are verifiably achieved, the key for patients and doctors is to find the right treatment at the right time for the right patient.
Suzanne Lentzsch, Columbia University, Herbert Irving Comprehensive Cancer Center, New York, NY: Relapse - Why It’s Not Necessarily the End of the World
There are approximately 15 approved novel agents for multiple myeloma
Treating myeloma is a challenge, for it changes a great deal over time (with spikes and relapses)
Your physician will always choose the best treatment for you with the minimum side effects
When to start treatment? No clear paths, but here are some general indicators:
Some clinical symptoms (CRAB-see Part 1 of this Round Table)
Biochemical progression (such as M spike over 0.5) with no symptoms
High-risk disease with progression
What are the recommended regimens?
Lenalidomide (Revlimid) combined with other drugs
Two additional drugs combined with the lenalidomide, this is a triplet therapy
Introduction to immunotherapy
Myeloma cells “hide from” immune system
They “disguise” themselves as normal cells, to not be identified as foreign
This creates a “tumor microenvironment” that nurtures them
Monoclonal antibodies that target myeloma cell markers (daratumumab an isatuximab are good examples)
Immunomodulatories (IMiDs) — End immune suppression caused by myeloma.
CAR T Cells — Boost myeloma-fighting cells (which are called T cells).
Types of antibodies.
Naked: used as single agent with nothing attached
Drug conjugates: a toxin is attached to kill myeloma cells
Bispecific: engineered to bind to myeloma cells with normal killer T cell and/or other therapeutic or chemotherapeutic agents
Cancer vaccine therapy
An injection combining myeloma proteins with immune cell-stimulating agents
Considered to be therapeutic, not preventive
May be used during consolidation phase after stem cell transplant
Small proteins that bind to myeloma cells and kill them
T cells are part of immune system that kill threatening cells
Each patient’s own T cells are engineered to target and kill myeloma cells directly before being infused back
Clinical trials show good responses in people with high-risk cytogenetics
Can cause CRS (cytokine release syndrome) because it ‘alerts’ immune system; it is a storm of inflammatory molecules that typically occurs 2 days after therapy
David Vesole, John Theurer Cancer Center, Hackensack, NJ: Lines of Therapy: Good News, Bad News
Current treatment for active myeloma if you are transplant eligible:
If not transplant eligible:
Induction followed by continuous maintenance therapy
When to consider “re-treatment”:
CRAB criteria are used to determine whether to treat for relapse
Differences between biochemical and symptomatic relapse need to be considered: a biochemical relapse shows an elevation of M-spike but no symptoms
Biochemical relapse (patients with an asymptomatic rise in M protein) can be observed to determine rate and nature of relapse, does not cause any harm
Symptomatic relapse is a strong indication for immediate treatment
For example, a 65-year-old patient with stage 1 myeloma received Revlimid, Velcade and dexamethasone induction therapy followed by a stem cell transplant was in complete remission for 3.5 years
After treatment: elevated M protein 0.6g/l with no symptoms (rising to more than 0.5 g/dl is considered to be disease progression)
3 months later: more elevated M protein of 0.8 g/l
6 months later: M protein 0.9 g/l
9 months later, M protein 1.5 g/dl, mild anemia
When to start treatment is difficult choice because side effects and quality of life have to be considered
If the protein is going up slowly with no symptoms, maybe a sit and wait approach would be good
However, when another symptom is presenting, treatment should be considered, so in this particular case, treatment at month 6 is correct.
How do we stage myeloma?
ISS (international staging system) uses specific markers run on your blood tests called Serum beta microglobulin, albumin (a protein in your blood), and LDH (lactate dehydrogenase)
Stage 1: Beta micrologbulin <3.5 mg/L, serum albumin >3.5 g/dL, normal LDH and standard risk genetics.
Stage 2: not stage 1 or 3
Stage 3: Beta micro globulin >5.5 mg/L + high-risk genetics or high LDH
Every myeloma patient is different, myeloma is independent, so one should not compare to another
Other things to think about when starting treatment: diabetes, neuropathy, cardiac problems, elderly or frail patients, renal disease, etc.
How do we choose therapy for myeloma?
Aggressiveness of disease is the strongest predictor
Also consider duration of remission, genetic factors, age, and co-morbidities
In general, if something worked before, you could try it again; however, I always give a little different cocktail to my patients.
We essentially mix and match; there are tons of combinations.
Alexander Lesokhin, Memorial Sloan Kettering Cancer Center, New York, NY: New in the Clinic
Some patients are resistant to many lines of therapy and still don’t achieve remission.
This is a medical breach that has to be filled. Some of the novel FDA-approved therapies for advanced myeloma include:
CAR-T cell (chimeric antigen receptor T cells) therapies: immune cells (T cells) are taken out, sent to a lab, and manipulated, put back into body, ready to target the myeloma
This is a one-time treatment, and has shown durable responses with three approved CAR T cell drugs:
There are no head-to-head comparisons between ide-cel and cilta-cel, but both have had impressive responses in relapsed and refractory disease
Antibody-drug conjugates mimic natural antibodies but to kill myeloma cells by sticking to BCMA (a specific marker in B cells, the cells that produce plasma cells)
T-cell recruiting Bi-Specifics, BiTEs
T cells (immune cells) have a particular receptor, and they “chew” waste out of your body (like mutated cells, cells with abnormal chromosomes, etc.), and this is what keeps us healthy. This process does not work in myeloma because it “hides” from t-cells
They mimic this process to kill the myeloma
Shown to work well (70% of response)
One advantage over CAR-T is that these BiTES are easily administered
What about multiple targets?
The idea is that multiple immune targets could be used sequentially to enhance their natural power
More than one target might kill more myeloma cells
More therapies have been and are being developed
Survival rates are still going up, “It’s a promising future for sure!”
Audience Questions & Answers
0:19 - While being in remission, what do we look for in terms of light chains?
5:22 - How much would a person’s history with bone damage at diagnosis play into when to treat relapse, would bone damage history make a difference in when to start?
7:16 - Re: drug treatment sequencing, will CAR T-cells replace a transplant in the future?
13:30 - Dara VTd (Velcade, thalidomide, dexamethasone) is currently approved in Germany, but I have an oncologist who can give me Dara VRd (Velcade, Revlimid, dexamethasone). Is the latter worth the considerable effort?
18:00 - Re: patient is currently MRD negative and in a trial that is trying to determine whether or not there’s going to be progression. So I was wondering if I am crazy or going downhill and just didn’t know it?
20:19 - Is there a role for allogenic transplant in relapsed myelomas or do the upcoming immunotherapies eliminate the need?
26:30 - I’ve been under 5 different treatments now. I’m on Blenrep (belantamab mafoditin) but I get double and blurry vision. I no longer want this treatment, but my doctor keeps saying I don’t have any other options. Is that true?
31:10 - Will stem cell transplants disappear due to immunotherapies?
36:43 - Re: T cell exhaustion after being in treatment for a long time. Does one’s immune system become more compromised and have a harder time fighting off infections. We have these stem cells stored away in a freezer and then use them to help boost your immune system again or even make your T-cells a little bit better?
41:10 - (Question re: COVID and myeloma.)
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about the author Andrea Robles
Andrea Robles is an International Medical Graduate, part of Healthtree’s patient navigator staff. She is committed to patient’s global wellness and finding a cure through research. She’s also a wife and mom of 3.