Last night I attended the meeting of our local Oncology Nursing Society chapter. Our guest speaker was Laura McBride, a research nurse at the Hackensack Cancer Center in New Jersey. For the last 10 years, she has been involved in groundbreaking clinical trials that have brought us the multiple myeloma (MM) treatment drugs such as Velcade, Revlimid, and now the latest FDA-approved Kyprolis (carfilzomib).
Kyprolis is a proteasome inhibitor indicated for the treatment of patients with MM who have received two prior therapies, including Velcade and an immunomodulator (e.g., Thalidomide, Revlimid), and demonstrated disease progression on or within 60 days of completing their last therapy.
Kyprolis is an IV infusion given over 10 minutes on two consecutive days, for three weeks (days 1, 2, 8, 9, 15, and 16) followed by a week off. Cycle 1 is given at a dose of 20 mg/m2 and subsequent cycles at 27 mg/m2. The drug comes in a 60 mg, single-dose vial, and a patient should never receive more than 59 mg total dose (or a BSA of 2.2). This is important because some larger patients may have a BSA that calculates above the 59 mg dose limit, and as nurses we must pay close attention to the dosage being administered.
Because many patients with MM have renal impairment and/or are at risk for tumor lysis syndrome, adequate hydration is important. It is recommended to give 250 ml to 500 ml of normal saline prior to the infusion of Kyprolis. Also, due to the risk of potential hypersensitivity reaction, premedication with Decadron 4mg (oral or IV) should be given.
As nurses, we play a critical role in educating patients and recognizing side effects early on. With Kyprolis, it is imperative to take a good health history before considering a patient for this drug. Fatal cardiac events have been reported within a day of Kyprolis infusion and thus, it is contraindicated to give the drug to a patient with a pre-existing cardiac history (e.g., congestive heart failure, myocardial infarction). Once patients receive this drug, common side effects (greater than 30 percent) to watch for include thrombocytopenia, nausea, diarrhea, low-grade fever, dyspnea, and anemia.
Currently, I have three patients with exposure to this drug:
- A 72-year-old female who received Kyprolis for four months and then randomly had what seemed to be a hypersensitivity reaction, which we thought strange considering her long tolerability to the drug. She was admitted to the hospital and ended up being diagnosed with pulmonary hypertension -- a rare side effect with Kyprolis. We followed guidelines for re-challenging her, but ultimately she developed repeated dyspnea and further toxicity, which caused us to discontinue therapy.
- A 46-year-old male has gone through two transplants and still has significant disease involving the bone marrow and unfavorable cytogenetics. He is in his second cycle and has struggled with headaches and thrombocytopenia. Interestingly, in Linda’s discussion, she mentioned that in the trial, they continued treating patients as long as their platelet count was above 25,000. This was good to learn, seeing as our practice, like so many, is largely unfamiliar with this drug.
- A 48-year-old male who had such significant toxicity to Velcade/Revlimid that we switched him to Kyprolis, all with the goal of getting him transplant-ready in the near future. His side effects are yet to be seen.
So do any of you have experience with this drug? Are you seeing some of the "not-so-common" side effects like pulmonary hypertension more than the trials reported?
Needless to say, there is still much to learn about this drug, including its use in combination with other agents. For patients living with a typically incurable disease, having yet another treatment option is exciting. Interestingly, 75 percent of the trial subjects had already received stem cell transplant and 28 percent had unfavorable cytogenetics. At the close of the trial, there was an overall response rate of 61 percent.