Velcade, Carfilzomib, Ixaomib Side Effects

Yes, proteasome inhibitors are effective MM therapies. However, velcade, carfilzomib and Ixaomib have side effects. It is extremely difficult for the newly diagnosed MM patient to experience a chemotherapy-induced side effect and not know what’s happening to them.

As a long-term MM survivor struggling with long-term side effects, I believe that MM patients do better when they understand and possibly prevent chemotherapy-induced side effects.

Proteasome inhibitor drugs

What are the most common side effects of proteasome inhibitors for the treatment of multiple myeloma?

Most Common Side Effects

Here are the most frequently reported side effects associated with proteasome inhibitors:

1. Peripheral Neuropathy

Especially common with bortezomib.
Tingling, numbness, pain, or weakness in the hands and feet.
Often dose-related and may be reversible with dose adjustments or drug changes.

2. Gastrointestinal Issues

Nausea, vomiting, diarrhea, or constipation.
These are common with all proteasome inhibitors but can usually be managed with supportive medications.

3. Fatigue

General tiredness or weakness is very common.
Can impact daily activities and quality of life.

4. Thrombocytopenia (Low Platelet Count)

Increases risk of bruising or bleeding.
Regular blood monitoring is required.

5. Anemia and Neutropenia

Low red or white blood cell counts.
May lead to fatigue or increased infection risk.

6. Infections

Higher risk of viral (like shingles) and bacterial infections due to immune suppression.
Prophylactic antivirals are often prescribed with bortezomib.

7. Cardiotoxicity (especially with carfilzomib)

Can cause high blood pressure, heart failure, or other cardiac complications.
Patients with a history of heart disease need close monitoring.

8. Liver Function Abnormalities

Elevated liver enzymes may be detected on blood tests.
Usually asymptomatic and reversible.

9. Skin Reactions

Rash or injection site reactions (for subcutaneous bortezomib).

What can be done to reduce the severity or possibly prevent side effects from protease inhibitors?

Integrative supplementation
Prehabilitate-
Baseline echocardiogram-
Take a therapy vacation-
Reduce the dose of the regimen-
Nutritional supplementation-

These are only a few of the possible strategies to discuss with your oncologist if you are facing PI side effects.

Email me at David.PeopleBeatingCancer@gmail.com with questions about Velcade, Carfilzomib, Ixaomib Side Effects.

Hang in there,

David Emerson

MM Survivor
MM Cancer Coach
Director PeopleBeatingCancer

Safety assessment of proteasome inhibitors real world adverse event analysis from the FAERS database

Abstract

Proteasome inhibitor analogs (PIs) have significantly improved the degree of remission and survival rate of patients with multiple myeloma. However, serious adverse events (AEs) have hindered their clinical application.

This study analyzed the AEs reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to determine the safety profile and differences for the PI drugs

bortezomib,
carfilzomib, and
ixazomib.

The reporting odds ratio (ROR) was used to detect safety signals. Significant safety signals were detected based on system-organ classification (SOC).

For bortezomib, the most significant SOC signal was “blood and lymphatic system disorders” (ROR = 3.47, 95% CI 3.37–3.57), while the most significant PT signal was “enteric neuropathy” (ROR = 134.96, 95% CI 45.67-398.79).

For carfilzomib, the most significant SOC signal being “blood and lymphatic system disorders” (ROR = 4.34, 95% CI 4.17–4.53), while the most significant PT signal was “light chain analysis increased” (ROR = 76.65, 95% CI 57.07-102.96).

For ixazomib, the most significant SOC signal was “gastrointestinal disorders” (ROR = 2.04, 95% CI 1.96–2.12), while the most significant PT signal was “light chain analysis increased” (ROR = 67.15, 95% CI 45.36–99.42). For bortezomib and carfilzomib, the top 20 reported PTs were consistent with AEs listed in the drug information.

For ixazomib, six unexpected AEs were observed:

asthenia,
malaise,
pyrexia,
decreased appetite,
dehydration,
and falls.

The PIs were consistent with the early failure model based on time-series analysis of the occurrence of adverse reactions to the drug. The data mined from FAERS generates new AE signals, and further clinical studies are needed to validate these findings…

Our study showed that in terms of SOC, IXZ was the only drug that showed a significant signal in “Gastrointestinal disorders.” CFZ showed a significant signal in “Cardiac disorders,” while BTZ was strongly associated with “Blood and lymphatic system disorders” and “Neoplasms benign, malignant and unspecified (incl cysts and polyps)…”

Conclusion

From 2004 Q1 to 2023 Q4, we conducted a detailed review of AE safety reports submitted to the FAERS database for BTZ, CFZ, and IXZ.

By analyzing 50,746 reports, we found that the most frequently reported AEs about IXZ that were not in the specification were Dehydration, Fall, and Decreased Appetite.

These PIs have different safety profiles and may cause serious adverse events that may lead to treatment interruption or patient death.

Clinicians should be fully aware of these safety differences in clinical care and adjust the treatment plan according to the patient’s specific situation in order to improve patient adherence and reduce the occurrence of adverse events.

Although some safety signals not indicated on the label have been identified in postmarketing monitoring, further prospective clinical studies are needed to validate these initial findings.”

velcade carfilzomib Ixaomib side effects velcade carfilzomib Ixaomib side effects

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