Abstract: FR-PO086
Renal Toxicities of Agents Used for CLL
Session Information
- AKI Clinical: Predictors
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Acute Kidney Injury
- 003 AKI: Clinical and Translational
Authors
- Wanchoo, Rimda, Hofstra Northwell School of Medicine, GREAT NECK, New York, United States
- Sakhiya, Vipulbhai, Hofstra Northwell School of Medicine, GREAT NECK, New York, United States
- Katsetos, John F, Hofstra Northwell School of Medicine, Lake Success, New York, United States
- Parikh, Nishita, Hofstra Northwell School of Medicine, GREAT NECK, New York, United States
- Bernabe, Carolina, Hofstra Northwell School of Medicine, Lake Success, New York, United States
- Barrientos, Jacqueline, CLL Research and Treatment Center, Lake Success, New York, United States
- Jhaveri, Kenar D., Hofstra Northwell School of Medicine, GREAT NECK, New York, United States
Background
Drugs with novel mechanisms of action and targeted therapies are being explored in both the pre-clinical and clinical settings for chronic lymphocytic leukemia (CLL). A possible limiting complication for these agents could be their nephrotoxic potential.
Methods
We reviewed the FDA adverse event reporting system (FAERS) quarterly legacy data file 3rd quarter of 2014 to 2nd quarter of 2017 for all recently approved targeted agents for CLL. Well established chemotherapy agents used in CLL such as cyclophosphamide and fludarabine were excluded. The adverse event terms queried were: hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, hypercalcemia, hyperkalemia, hypernatremia, hyperphosphatemia, proteinuria, renal failure acute, acute kidney injury, tumor lysis syndrome(TLS), hypertension, and nephritis. We reviewed the literature using pubmed, case series and the registrational studies of these agents for any reported nephrotoxicity. We compared renal toxicities of the newer agents such as ibrutinib, idelalisib, obinutuzumab, and venetoclax(to older targeted agents such as alemtuzumab and ofatumumab).
Results
The table here summarizes the drugs studied and results found. Ofatumumab, alemtuzumab and ibrutinib were the top three offenders with AKI as the most common finding reported followed by TLS and hyponatremia. The newer agents used to treat CLL had fewer renal toxicities than the older agents. The mechanism of AKI is likely related to TLS in most of these agents. The literature reviewed in the FAERS reported additional toxicities of the newer agents such as TLS with venetoclax that was fatal leading to early trial modifications.
Conclusion
Novel targeted agents are changing the CLL treatment paradigm with ensuing reports of nephrotoxic events such as AKI and TLS. As these drugs become more widely used, knowledge of novel agents used in CLL and their possible renal toxicities is important for the practicing nephrologists and the hematologists.
Table
| Name | Renal injury | Hyponatremia | Hypokalemia | Hypophosphatemia | Hypomagnesemia | Hyperkalemia | Proteinuria | Tumor Lysis Syndrome | Grand Total |
| Alemtuzumab | 25 | 4 | 0 | 0 | 0 | 0 | 3 | 1 | 33 |
| Ofatumumab | 29 | 7 | 6 | 0 | 0 | 3 | 0 | 16 | 61 |
| Ibrutinib | 9 | 9 | 5 | 4 | 1 | 3 | 0 | 6 | 37 |
| Idelalisib | 4 | 1 | 2 | 0 | 0 | 3 | 0 | 8 | 18 |
| Obinutuzumab | 10 | 0 | 0 | 1 | 0 | 1 | 0 | 8 | 20 |
| Venetoclax | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 2 | 6 |