by Dr. C.H. Weaver M.D. updated 3/2019
The U.S. Food and Drug Administration (FDA) has approved Kyprolis™ (carfilzomib) for the treatment of patients with multiple myeloma because it prolongs survival duration. Kyprolis is approved for use as a single drug and in combination with dexamethasone for patients with recurrent multiple myeloma who have received one to three prior treatments.
Kyprolis is a proteasome inhibitor. Proteasomes are naturally occurring components in cells that aid in the breakdown and removal of abnormal or unneeded proteins. Proteasome inhibitors interfere with the ability of proteasomes to remove these abnormal proteins, leading to the excessive accumulation and build-up of these proteins within cells, which results in the blocking of normal cellular functions.
Kyprolis Improves Survival in Recurrent Multiple Myeloma
Researchers reported survival results from a large, international clinical trial referred to as the ASPIRE trial. The ASPIRE trial directly compared two treatment regimens among patients with multiple myeloma who had received 1-3 prior therapies. One group of patients was treated with Kyprolis/Revlimid/dexamethasone (KRd) and the second group was treated with Revlimid/dexamethasone (Rd)
- Among patients who had received only one prior therapy that included bortezomib, overall survival was improved by one year (12 months) in the group treated with KRd, compared with those treated with Rd.
- Among patients who had received only one prior therapy that did not include bortezomib, overall survival was improved by 7.9 months in the group treated with KRd, compared to those treated with Rd.
- Among patients who received two or more prior therapies, overall survival was improved by 6.5 months in the group treated with KRd, compared to those treated with Rd.
- Patients who were considered to be at a low risk of developing a recurrence based on specified disease characteristics had not yet reached median survival time for the group treated with KRd had not yet been reached at the time data was collected, and was 58 months for those treated with Rd.
- Patients who were considered to be at an average risk of developing a recurrence had a median overall survival of 45.4 months if treated with KRd, and 41.2 months for those treated with Rd.
- Patients who were considered to be at a high risk of developing a recurrence had a median overall survival 23.3 months for those treated with KRd and 18.8 months for those treated with Rd.
The most common side effects of Kyprolis are fatigue, anemia, nausea, low platelet counts, shortness of breath, diarrhea, and fever. Some patients experience serious side effects, including heart failure.
ENDEAVOR Study Demonstrates Superiority of Kyprolis Over Velcade
The ENDEAVOR study is the first of two head-to-head studies for Kyprolis versus Velcade, an established proteasome inhibitor, currently approved to treat multiple myeloma. The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone, versus Velcade with low-dose dexamethasone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. This study was conducted at 235 sites worldwide.
The results of the study reveled that patients with relapsed multiple myeloma treated with Kyprolis lived twice as long without their disease worsening compared to Velcade. Kyprolis treated patients survived on average 18.7 months compared to only 9.4 months for those receiving Velcade.
The Kyprolis combination was also reported to have higher overall response rates and less neuropathy.
- The median progression-free survival (time from initiation of treatment until disease progression or death) was approximately 18.7 months for patients treated with Kyprolis/dexamethasone, compared with only 9.4 months for patients treated with bortezomib/dexamethasone.
- Overall, the tolerability of Kyprolis/dexamethasone was comparable to that of bortezomib/dexamethasone.
- Overall anti-cancer responses occurred in 77% of patients treated with Kyprolis/dexamethasone and 63% of patients treated with bortezomib/dexamethasone.
- Amgen press release. FDA Approves New Kyprolis® (Carfilzomib) Combination Therapy For The Treatment Of Patients With Relapsed Or Refractory Multiple Myeloma. Available at: . Accessed January 22, 2016.
- Amgen. 2015. Phase 3 Head-to-Head ENDEAVOR Study Demonstrates Superiority Of Kyprolis® (carfilzomib) Over Velcade® (bortezomib) In Patients With Relapsed Multiple Myeloma. Mar. 1.
- Stewart K, Siegel D, Ludwig H, et al. Overall survival (OS) of patients with relapsed/refractory multiple myeloma (RRMM) treated with Kyprolis, Revlimid, and dexamethasone (KRd) versus Revlimid and dexamethasone (Rd): Final analysis from the randomized phase 3 Aspire trial. Proceedings from the 2017 annual meeting of the American Society of Hematology (ASH). Abstract #743. Retrieved from ash.confex.com/ash/2017/webprogram/Paper102318.html.