[Ruchi]

Can Kyprolis cause elevated creatinine levels?

by Ruchi on Thu May 09, 2019 9:47 am

My mother is on a Kyprolis (carfilzomib), bendamustine (Treanda), and dexamethasone regimen since one month after her kappa light chains got very high. She took bendamustine (100 mg) for the first two weeks along with Kyprolis (60 mg) and dex (40 mg) and for the third week her Kyprolis dose was increased to 80 mg along with only dex (40 mg).Fourth week was off.

Her creatinine at the start of third week was 1.34 (range is 0.52-1.04 mg/dL) and at the end of fourth week is 1.52.

My question is, could the Kyprolis be the cause of the increased creatinine level?

My mother's hemoglobin had dropped to 7.4, after which the doctor put her on erythropoietin injections for 3 weeks. Now since one month her hemoglobin remains between 9-10 without this injections. All her other CBC values are in normal range.

Ruchi

[Multibilly]

Re: Can Kyprolis cause elevated creatinine levels?

by Multibilly on Thu May 09, 2019 12:29 pm

Hi Ruchi,

Yes, carflizomib can impact kidney function and therefore elevate creatinine levels (and lower one's eGFR). You should should also be aware that it can cause cardiac issues (as several folks on this forum have reported) and that cardiac function should also be monitored closely while on this drug. See:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202714s025lbl.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738981/

We also evaluated the effects of carfilzomib on renal functions, excluding renal dysfunction, which were associated with disease progression: 22 patients (37%) had grade ≥ 1 creatinine increase (grade 1, 18%; grade 2, 17%; grade 3, 2%), 17 (28%) had acute kidney injury grade ≥ 1 (grade 1, 25%; grade 3, 3%), and 21 (35%) had a reduction of estimated glomerular filtration rate (eGFR) ≥25%. Similar to previous reports,14 this decrease was transient in 13 (62%) of 21 patients and occurred within the first cycle of carfilzomib in 9 (43%) of 21 patients. Median time until return of eGFR to baseline was 15 days (range, 7-28 days). With higher doses of carfilzomib, eGFR reduction was more common: 22%, 33%, and 52% for doses of 27 mg/m2, 36 mg/m2, and 56 mg/m2, respectively (P = .093). Hydration amount has been correlated with the risk of renal insufficiency, and increased fluid intake has been suggested to be protective.14 No baseline factor, including age, diabetes, or medication (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers or diuretics) correlated with eGFR reduction. However, in 11 (55%) of 20 patients with baseline eGFR <60 mL/min, eGFR improved to >60 mL/min; thus, carfilzomib is a treatment option for patients with myeloma-related renal dysfunction.

[Ruchi]

Re: Can Kyprolis cause elevated creatinine levels?

by Ruchi on Thu May 09, 2019 3:07 pm

Thank you so much, Multibilly, for your quick and helpful post.

I am aware of the cardiac issues the drug can cause, and the oncologist monitors her heart function by periodic 3D ECG's. It was good to know the kidney-related side effects due to Kyprolis (carfilzomib).

Mother was treated with carfilzomib before along with Revlimid and dexamethasone (which did not give her long response), and at that time her creatinine after first dose went from 1.5 to 1.2. After that, it fluctuated between 1.2 and 1.4. This time it increased from 1.2 to 1.52 during the course of treatment (could be due to higher dose of carfilzomib), so I was concerned if the treatment was working and the light chains were not impacting the kidneys. But this seems hopeful that carfilzomib could be the reason of elevated creatinine values.

Thanks again for your help. I really appreciate it.

Ruchi