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Multiple Myeloma an incurable disease, but I have spent the last 25 years in remission using a blend of conventional oncology and evidence-based nutrition, supplementation, and lifestyle therapies from peer-reviewed studies that your oncologist probably hasn't told you about.
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Sarcopenia Weakens CAR-T Myeloma
What does it mean when I say that sarcopenia weakens CAR-T in myeloma? The study linked below used a lot of jargon but my read of the study is that the skinny, weak MM patients have worse CAR-T outcomes than big, strong MM patients.
What is sarcopenia?
Sarcopenia is a condition characterized by a gradual loss of muscle mass, strength, and function with age. It is a common age-related decline that can affect older adults, particularly those over 65 years old.
Causes:
-
- Aging
- Reduced physical activity
- Nutritional deficiencies
- Hormonal changes (e.g., decreased testosterone in men, decreased estrogen in women)
- Chronic diseases (e.g., diabetes, heart disease)
- Certain medications
The challenge that MM patients face is that SOC treatments, especially an ASCT, cause sarcopenia.
Results from the Health ABC study on accelerated sarcopenia in older cancer patients
The solution?
I don’t like to sound like a broken record but MM patients, beginning with their initial diagnosis, my exercise. I know that many of us don’t feel like exercising much of the time. Especially if the patient is living with bone problems.
But study after study cites prehabilitation in general, and exercise specifically, as contributing to fewer side effects and longer progression-free and overall survival.
I am a long-term MM survivor. Email me at David.PeopleBeatingCancer@gmail.com with questions you have about conventional and non-conventional MM therapies.
Hang in there,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Body composition predicts poor outcomes and reveals immunometabolic dysfunction via single-cell profiling in anti-BCMA CAR T-treated myeloma
Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment of relapsed or refractory multiple myeloma (RRMM), yet outcomes remain heterogenous. The prognostic role of body composition in this context is unknown.
We retrospectively analyzed 108 RRMM patients treated with anti-B-cell maturation antigen (BCMA) CAR T-cell therapy. Pre-treatment Computed tomography imaging was utilized to quantify
- total adipose tissue (TAT),
- subcutaneous adipose tissue (SAT),
- visceral adipose tissue (VAT),
- and skeletal muscle area to assess sarcopenia.
Longitudinal flow cytometric and single-cell multi-omic analyses were conducted to characterize the quantitative and qualitative influences of body composition on the immune microenvironment.
Patients with BMI <25 kg/m2 experienced significantly worse overall survival (OS) compared to high-BMI patients.
Reduced TAT, primarily driven by low SAT, was associated with inferior OS, diminished response and elevated soluble BCMA. Sarcopenia independently predicted poorer OS, while progression-free survival was unaffected by the respective parameters.
Low SAT and sarcopenia correlated with lower bystander T-cell counts at leukapheresis. Longitudinal T-cell receptor sequencing and single-cell transcriptomics revealed diminished cytotoxic and interferon signaling, reduced T-cell clonality, and increased oxidative phosphorylation activity following CAR T-cell infusion.
Our findings identify low SAT and sarcopenia as prognostic biomarkers that influence survival, therapeutic response, and immunometabolic profiles. Their quantification through standard imaging techniques offers a cost-effective strategy for early risk stratification and individualized management in CAR T-cell therapy.
Sarcopenia Prevalence and Influence on the Development of Toxicity and Length of Stay in Patients with Relapsed and Refractory Myeloma Treated with Commercial Anti-BCMA CART Cells
Abstract
Background Sarcopenic muscle loss has well-documented adverse impacts on treatment outcomes and mortality across cancer types and is particularly prevalent in patients with multiple myeloma, reported in 54% of newly diagnosed patients (Nandakumar ASCO 2022).
Two chimeric antigen receptor T-cell (CAR-T) constructs have been FDA approved for relapsed/refractory multiple myeloma (RRMM) after exposure to at least 4 prior lines of therapy.
MM Treatment combinations frequently incorporate high dose dexamethasone, well known to cause muscle atrophy, and patients may be on therapy for many years prior to becoming eligible for commercial products with associated detrimental effects from cumulative toxicities…
Results The cohort consisted of 61 patients, 55 (90%) received ide-cel and 6 (10%) received cilta-cel. Baseline characteristics are summarized in Table 1. Of these 16 (26%) were ≥70 years at the time of treatment and 36 (59%) had co-morbidity index >2 at the time of therapy (Sorror, Blood 2005).
All scans were performed a median of 16 days prior to CAR-T administration (range 2-90). Prior to CAR-T administration 47 (77%) of patients met criteria for sarcopenia based on their pre-LD chemo restaging imaging.
Male patients were more likely than women to meet criteria for sarcopenia (89% vs 62%, p=0.01) and 31 (50%) met criteria for sarcopenic overweight or obesity. Sarcopenic patients had poorer baseline performance status ECOG >=2 (23% vs 7%, p=0.17), higher baseline ferritin (p=0.08) and higher baseline tumor burden as defined by >50% marrow involvement (40% vs 14%, p=0.08) when compared to non-sarcopenic patients, although not significant at the P=0.05 level.
The majority (63%) of sarcopenic patients did not meet criteria for registration trials. No significant relationship was found between the presence of sarcopenia and the development of cytokine release syndrome, but all patients who developed neurotoxicity (any grade) had underlying sarcopenia (any grade ICANS 12/47, 26% vs 0%, p=0.04).
A greater proportion of sarcopenic patients had extended lengths of stay >=9 days 51% vs 21%, p=0.05). In total 24/61 (39%) were recommended for post-discharge rehab/physical therapy, of whom the majority (N=20) had baseline sarcopenia. Similarly, 13/61 (21%) required additional supports at home on discharge, N=10 with baseline sarcopenia.
Conclusion Sarcopenia is highly prevalent, found in 77% of patients attending for BCMA-directed CAR-T therapy in the commercial setting. We have shown that analysis of body habitus is straightforward to perform using images acquired as standard and could inform practice.
In the real-world setting, sarcopenic patients appear to be at higher risk of developing neurotoxicity, although this merits further investigation. Although high prevalence of sarcopenia in this sample may preclude statistical detection of its adverse clinical impacts, it is clearly a significant clinical issue for patients undergoing complex immunotherapies for MM and warrants further research and intervention.
Pre-habilitation strategies may be beneficial while patients are awaiting apheresis availability, or during cell manufacturing.
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