Cardiotoxicity Prevention for Myeloma

If conventional oncology emphasizes the importance of preventing cardiotoxicity, then it is reasonable to believe that cardiotoxicity prevention for myeloma is essential.

Cardiotoxicity from chemotherapy regimens, causing chemotherapy-induced cardiomyopathy, is a life-threatening side effect of aggressive MM therapy. I was diagnosed with CIC fully 15 years after my autologous stem cell transplant.

The average age of MM patients is 70. Any existing heart health issues complicate this problem further.

Which chemotherapy regimens used for the treatment of multiple myeloma are cardiotoxic?

1. Anthracyclines (especially in older regimens)

Doxorubicin (used in the older VAD regimen: Vincristine + Doxorubicin + Dexamethasone).
- Cardiotoxicity: Dose-dependent, cumulative, irreversible cardiomyopathy, arrhythmias, congestive heart failure (CHF).
- Modern regimens rarely use anthracyclines because of this risk.

2. Alkylating agents

Cyclophosphamide (CyBorD: Cyclophosphamide + Bortezomib + Dexamethasone).
- Rare but can cause myocarditis, pericarditis, arrhythmias, and heart failure at high doses.
- Risk is generally lower at MM dosing levels compared to stem-cell conditioning.
Melphalan (used in conditioning before autologous stem cell transplant).
- High-dose melphalan can cause atrial fibrillation, arrhythmias, and rare CHF.

3. Proteasome inhibitors

Carfilzomib (Kyprolis).
- Strongly linked to cardiotoxicity: heart failure, hypertension, ischemia, arrhythmias, sudden cardiac death.
- Cardiac events occur in up to 10–25% of patients in some trials.
- Mechanism: endothelial dysfunction, oxidative stress, and myocardial strain.
Bortezomib (Velcade).
- Much lower cardiac risk, but rare cases of CHF, arrhythmias, and ischemia reported.
Ixazomib (oral).
- Generally less cardiotoxic than carfilzomib, but occasional reports of arrhythmia and heart failure.

4. Immunomodulatory drugs (IMiDs)

Thalidomide, Lenalidomide, Pomalidomide.
- Indirect cardiotoxicity: increased risk of venous thromboembolism (VTE), pulmonary embolism, and myocardial infarction (especially when combined with steroids).
- Not typically associated with direct myocardial toxicity, but ischemic events are a concern.

5. Corticosteroids (Dexamethasone, Prednisone)

Cause fluid retention, hypertension, arrhythmias, and worsening of pre-existing heart failure.
Not directly cardiotoxic but can exacerbate cardiac comorbidities.

Summary Table

Drug/Class	Regimen Examples	Cardiac Risks
Anthracyclines (Doxorubicin)	VAD (rarely used now)	CHF, arrhythmia, cardiomyopathy
Cyclophosphamide	CyBorD	Arrhythmia, myocarditis, CHF (rare at MM doses)
Melphalan (high-dose)	ASCT conditioning	Arrhythmia, atrial fibrillation, CHF
Carfilzomib	KRd, Kd	HF, ischemia, hypertension, arrhythmia (highest risk)
Bortezomib/Ixazomib	VRd, IRd	Rare CHF, arrhythmia
IMiDs (Thal, Len, Pom)	VRd, Rd, Pom-dex	Thrombosis, MI, stroke
Steroids	All combinations	Fluid retention, hypertension, arrhythmia

👉 The most clinically significant cardiotoxic agents in modern MM therapy are:

Carfilzomib (direct cardiac risk)
Anthracyclines (in older regimens)
IMiDs + steroids (indirect ischemic/thrombotic risk)

The solution, in my experience anyway, is more involved than what the article linked below calls for. Yes, cardio-oncology as a specialty would help MM patients.

I believe that non-conventional heart-healthy nutrition, supplementation and lifestyle therapies before, during, and after conventional treatments may reduce or even prevent chemotherapy-induced cardiomyopathy.

This heart-healthy prehabilitation would be as important as normal prehabilitation.

Please email me at David.PeopleBeatingCancer@gmail.com if you have questions about managing your MM with both conventional and non-conventional MM therapies.

Good luck,

David Emerson

MM Survivor
MM Cancer Coach
Director PeopleBeatingCancer

Cardiotoxicity Induced by Anticancer Therapies: A Call for Integrated Cardio-Oncology Practice

Abstract

The introduction of novel oncologic therapies, including targeted agents, immunotherapies, and antibody–drug conjugates, has transformed the therapeutic landscape of cancer care. This evolution has resulted in a dual clinical scenario; while survival outcomes have markedly improved, leading to a growing population of long-term cancer survivors, an increasing incidence of previously unrecognized treatment-related toxicities has emerged.

Among these, cardiovascular adverse events represent some of the most prevalent and clinically significant complications observed in both conventional chemotherapy and modern therapeutic regimens.

Cardiotoxicity has become a major concern, with the potential to adversely affect not only cardiovascular health but also the continuity and efficacy of oncologic treatments, thereby impacting overall survival. This opinion paper synthesizes current evidence, identifies critical gaps in knowledge, and advocates for a multidisciplinary, evidence-based framework to guide the prevention, early detection, and optimal management of cardiotoxicity associated with anticancer therapies…

Therapeutic Agents Associated with Cardiotoxicity

Cancer-therapy-related cardiotoxicity includes various conditions that may be induced by different classes of agents, such as chemotherapeutic drugs like anthracyclines, proteasome inhibitors, and microtubule inhibitors; targeted therapies (e.g., anti-HER2 drugs, anti-angiogenic agents); immunotherapy; and newer drugs, such as ADCs…

Cardiotoxicity Induced by Proteasome Inhibitors

Proteasome inhibitors (PIs), including Carfilzomib and Bortezomib, are pivotal in the treatment of multiple myeloma. However, their use is associated with varying degrees of cardiovascular toxicity, necessitating careful consideration in clinical practice [93].

Carfilzomib is an irreversible PI that inhibits the β2 and β5 subunits of the proteasome. Preclinical studies demonstrated Carfilzomib-induced cardiotoxicity in young adult mice, highlighting the potential for cardiac damage in vivo [94].

A meta-analysis indicated that Carfilzomib significantly increases the risk of cardiotoxicity, with odds ratios of 2.34 for all-grade and 2.69 for high-grade cardiotoxicity [95]. Furthermore, a study analyzing FDA Adverse Event Reporting System (FAERS) data reported an 18.2% rate of any cardiovascular adverse event associated with Carfilzomib, with event rates ranging from 0% to 52% [96].

These findings underscore the importance of monitoring cardiac function in patients receiving Carfilzomib.

Bortezomib, in contrast, is a reversible PI that primarily inhibits the β5 subunit. While it has been associated with a lower incidence of CV adverse events compared to Carfilzomib, preclinical data suggest that Bortezomib can also induce cardiotoxicity.

A study by Wesley et al. assessed the effects of Carfilzomib and Bortezomib on cardiac function in animal models, observing decreased fractional shortening and left ventricular ejection fraction, indicating potential cardiotoxic effects of both agents [97].

A real-world study involving 395 patients found that 20.8% experienced any grade of CV adverse events, with hypertension being the most common [98]. Additionally, a systematic review and meta-analysis reported that high-grade cardiotoxicity was more frequent with Bortezomib compared to the control group, with an odds ratio of 1.67. However, the overall cardiovascular risk remains lower than that associated with Carfilzomib [99]…

Conclusions

Cardiotoxicity has emerged as a major challenge in modern oncology, with increasing numbers of patients affected by cardiovascular complications from both traditional and novel cancer therapies. This evolving scenario calls for a proactive, structured, and multidisciplinary cardio-oncology approach integrated into every phase of the cancer care continuum. Timely cardiovascular risk assessment, evidence-based surveillance protocols, and close collaboration between cardiologists and oncologists are essential to optimize outcomes, avoid treatment interruptions, and ensure long-term survivorship. The development of dedicated cardio-oncology services, supported by institutional commitment and standardized training pathways, is now a clinical necessity…”

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