The Side Effect Profile of Carfilzomib: from Clinical Trials to Clinical Practice

REVIEW

The Side Effect Profile of Carfilzomib: From Clinical Trials to Clinical Practice

LAURA McBRIDE, RN, BSN, OCN®, CCRP, and CHRISTINE O. SAMUEL, RN, BSN, OCN®, CCRP

From John Theurer Cancer Center at Hacken- sack University Medical Center, Hackensack, Abstract New Jersey, and MD Anderson Cancer Center, Treatment of patients with relapsed and/or refractory multiple myeloma Houston, Texas (RR MM) is challenging due to the heterogeneity of the disease, patient Authors' disclosures of potential conflicts of comorbidities, and side effects of individual treatments. Carfilzomib, a interest are found at the end of this article. selective proteasome inhibitor that has shown safety and efficacy as Correspondence to: Christine O. Samuel, RN, a single agent in phase I and II trials, was recently approved by the US BSN, OCN®, CCRP, Lymphoma/Myeloma Center, Food and Drug Administration for RR MM. The aim of this review is MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. to summarize adverse events (AEs) in patients with MM treated with E-mail: [email protected] single-agent carfilzomib in phase II clinical studies and to provide insight © 2013 Harborside Press® into the prevention and management of these AEs from the perspective of the advanced practitioner (AP). Data from a cross-trial safety analysis describing the safety and tolerability of single-agent carfilzomib in 526 patients with RR MM who received carfilzomib in four phase II trials are summarized. Additional information is included based on AP clinical practice experience gained in the clinical trial setting. Guidelines are suggested to assist with patient management prior to carfilzomib treatment, including hydration and prophylactic medication, as well as the management of hematologic AEs, fatigue, and dyspnea during treatment. Infre- quent but potentially serious AEs, including cardiac and renal complications, are also reviewed. Adverse events in varying frequencies occur in response to carfilzomib, but they can be managed with prophylaxis and routine care. Utilizing the clinical practice experience with carfilzomib presented here should help to maximize the efficacy of carfilzomib while minimizing AEs and potential discomfort in patients with late-stage MM. J Adv Pract Oncol 2013;4(Suppl 1):22–30

ultiple myeloma (MM) Multiple myeloma mainly mani- is a hematologic can- fests as hypercalcemia, renal insuf- cer that is expected ficiency, anemia, and bone lesions, to result in more than mnemonically referred to as CRAB M10,700 deaths in the United States in (Raab, Podar, Breitkreutz, Richard- 2013 (American Cancer Society, 2013). son, & Anderson, 2009). Patients can

J Adv Pract Oncol 22 AdvancedPractitioner.com SIDE EFFECT PROFILE OF CARFILZOMIB REVIEW range from asymptomatic to severely disabled, de- these events from an advanced practitioner (AP) pending on where they are in the course of their perspective, based on clinical experience in the phase disease (Pingali et al., 2012). Although new treat- II trial setting as well as current use. ments have improved outcomes for patients with MM, the disease remains incurable and is associ- ADVERSE EVENTS IN CLINICAL ated with limited survival (Laubach et al., 2011; TRIALS AND CLINICAL PRACTICE Ludwig et al., 2011). A cross-trial safety analysis has been reported Along with the clinical manifestations of the describing the safety and tolerability of single-agent disease, it is important to be aware of the com- carfilzomib in 526 patients with RR MM who received mon side effects of MM treatments; these can carfilzomib in four phase II trials: PX-171-003-A0, include myelosuppression, infection, peripheral PX-171-003-A1, PX-171-004, and PX-171-005 (Har- neuropathy (PN), thromboembolic complica- vey et al., 2012; Lonial, Niesvizky, McCulloch, Ra- tions, and untoward cardiac side effects (Pingali, jangam, & Vij, 2012; Martin et al., 2012; Nooka et al., Haddad, & Saad, 2012). Treatment of patients 2012; Siegel et al., 2013). The most common hema- with relapsed and/or refractory (RR) MM is par- tologic AEs were anemia and thrombocytopenia, ticularly challenging due to the heterogeneity of while the most common nonhematologic AEs were the disease, patient comorbidities, complications fatigue, nausea, dyspnea, diarrhea, pyrexia, and up- caused by the disease, and the adverse events per respiratory tract infections; see Table 1 (Onyx (AEs) associated with individual treatments Pharmaceuticals, 2012; Siegel et al., 2013). The most (Dimopoulos & Terpos, 2010; Laubach et al., 2011; common events ≥ grade 3 were mainly hematologic Mohty et al., 2012; van de Donk et al., 2011). and included thrombocytopenia (23.4%), anemia Carfilzomib (Kyprolis) is a proteasome inhibi- (22.4%), lymphopenia (18.1%), pneumonia (10.5%), tor that has shown safety and efficacy in patients and neutropenia (10.3%). Of the 526 patients in this with RR MM in both phase I (Alsina et al., 2012; analysis, 14.6% required a dose modification and O’Connor et al., 2009) and phase II trials (Badros 14.8% discontinued treatment due to an AE (Siegel et al., 2013; Jagannath et al., 2012; Siegel et al., 2012; et al., 2013). Vij et al., 2012a, 2012b). Carfilzomib selectively Adverse events frequently observed in the and irreversibly inhibits the chymotrypsin-like clinical setting can be found in Table 2, listed activities of both the constitutive proteasome and according to relative observed frequency; these the immunoproteasome via a binding mechanism events are generally consistent with those reported that is distinct from that of the reversible inhibitor from the clinical trials noted above. Adverse events bortezomib (Velcade; Arastu-Kapur et al., 2011). most commonly appearing in the first 24 to 48 Carfilzomib has a short half-life (Badros et al., hours include infusion-related reactions charac- 2013; O’Connor et al., 2009), which, along with its terized by flu-like symptoms including fever, rigor, selective binding and lack of off-target effects, may chills, and dyspnea; injection site–related reactions explain the favorable safety profile of the drug. such as phlebitis; increases in certain laboratory Carfilzomib was recently approved by the US values (including creatinine and transaminases); Food and Drug Administration (FDA) for patients and elevations in blood pressure. Other com- with RR MM. Approval was based on results from mon AEs that can appear either early or in later the pivotal PX-171-003-A1 trial (ClinicalTrials.gov treatment cycles include fatigue, gastrointestinal identifier NCT00511238) for efficacy and safety AEs, hematologic AEs, dyspnea not related to initial and studies PX-171-003-A0 (NCT00511238), dosing, infections, and similar increases in labora- PX-171-004 (NCT00530816), and PX-171-005 tory values described above. Cardiac, renal, and (NCT00721734) for safety (Onyx Pharmaceuticals, hepatic AEs are reported infrequently but can lead 2012; Siegel et al., 2012, 2013). to serious complications. To maximize the benefits of carfilzomib, it is important to understand the possible AEs associated RISK MANAGEMENT with its administration. The objective of this review is Baseline Assessment to summarize both common and infrequent clinically It is well-accepted that patient education is relevant AEs observed following carfilzomib use an important tool that can improve treatment. and to provide insight into the management of In order to obtain a thorough baseline profile of

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Table 1. Incidence of Treatment-Emergent Adverse Events in > 10% of Patients From 526 Patients in Four Phase II Clinical Trials

Patients, N = 526 Event All grades Grade 3 Grade 4 Hematologic Anemia 246 (46.8%) 111 (21.1%) 7 (1.3%) Thrombocytopenia 191 (36.3%) 69 (13.1%) 54 (10.3%) Lymphopenia 126 (24.0%) 84 (16.0%) 11 (2.1%) Neutropenia 109 (20.7%) 50 (9.5%) 4 (0.8%) Leukopenia 71 (13.5%) 27 (5.1%) 1 (0.2%) Nonhematologic Fatigue 292 (55.5%) 38 (7.2%) 2 (0.4%) Nausea 236 (44.9%) 7 (1.3%) 0 Dyspnea 182 (34.6%) 25 (4.8%) 1 (0.2%)a Diarrhea 172 (32.7%) 4 (0.8%) 1 (0.2%) Pyrexia 160 (30.4%) 7 (1.3%) 2 (0.4%) Upper respiratory tract infection 149 (28.3%) 17 (3.2%) 0 Headache 145 (27.6%) 7 (1.3%) 0 Cough 137 (26.0%) 1 (0.2%) 0 Blood creatinine increased 127 (24.1%) 13 (2.5%) 1 (0.2%) Edema peripheral 126 (24.0%) 3 (0.6%) 0 Vomiting 117 (22.2%) 5 (1.0%) 0 Constipation 110 (20.9%) 1 (0.2%) 0 Insomnia 94 (17.9%) 0 0 Chills 84 (16.0%) 1 (0.2%) 0 Arthralgia 83 (15.8%) 7 (1.3%) 0 Muscle spasms 76 (14.4%) 2 (0.4%) 0 Hypertension 75 (14.3%) 15 (2.9%) 2 (0.4%) Hypokalemia 72 (13.7%) 14 (2.7%) 3 (0.6%) Hypomagnesemia 71 (13.5%) 2 (0.4%) 0 Pain in extremity 70 (13.3%) 7 (1.3%) 0 Pneumonia 67 (12.7%) 52 (9.9%) 3 (0.6%)a Aspartate aminotransferase increased 66 (12.5%) 15 (2.9%) 1 (0.2%) Dizziness 66 (12.5%) 5 (1.0%) 1 (0.2%) Hypoesthesia 64 (12.2%) 3 (0.6%) 0 Hypophosphatemia 55 (10.5%) 24 (4.6%) 3 (0.6%) Hyponatremia 54 (10.3%) 31 (5.9%) 3 (0.6%) Note. Information adapted from Onyx Pharmaceuticals (2012). aOne event was of grade 5 severity. the patient, it is helpful to educate the patient have been exposed to multiple therapies, such on how to provide an adequate medical history. as those patients with RR MM, it is important Particularly in individuals who are older and to consider comorbid conditions and to have a

J Adv Pract Oncol 24 AdvancedPractitioner.com SIDE EFFECT PROFILE OF CARFILZOMIB REVIEW thorough knowledge of the patient’s medical history. Performing a complete initial assessment Table 2. Relative Observed Frequency of Adverse Events Associated With Carfilzomib is necessary to establish a baseline profile. In all patients with MM, baseline evaluation of cardiac Frequently observed • Fatigue and renal function is essential. Given that PN can • Dyspnea be associated with treatment of MM (Mohty et • Hematologic AEs al., 2010), a baseline neuropathy examination is Thrombocytopenia Anemia important as well. However, neuropathy is not a Neutropenia significant concern with carfilzomib treatment • Upper respiratory tract infections and pneumonia (Martin et al., 2012). It is necessary to obtain baseline Occasionally observed vital signs and monitor for changes during and • Gastrointestinal after dosing, particularly in patients with a history Nausea Diarrhea of hypertension. A thorough review of previous • Flu-like infusion-related reactions and current medications is essential, especially for • Other infusion-related complications (e.g., site reactions) patients with a history of cardiovascular disease. • Increases in laboratory values or blood pressure During this initial evaluation, patients should be • Electrolyte imbalances advised that concomitant medication records • Other infections (e.g., urinary tract infections) need to be updated frequently in order to properly Infrequently observed anticipate and manage potential AEs. Additionally, • Peripheral neuropathy a patient’s weight should be recorded at baseline Infrequently observed but potentially serious • Cardiac and at least once weekly during treatment. • Renal It is important to educate the patient on the • Hepatic need for prophylactic medication (which may vary according to the patient) to help manage AEs. It is also helpful to educate both patients and The carfilzomib prescribing information dos- caregivers on the side effects that may occur with ing guidelines recommend that patients receive carfilzomib treatment, making sure they are aware 250 to 500 mL of normal saline or other appropri- of what should be reported and when to report it. ate intravenous (IV) fluid prior to the administra- Empowering patients and their caregivers with tion of carfilzomib and the same amount following this knowledge will enable APs to manage patients administration, as needed (Onyx Pharmaceuticals, who are taking carfilzomib more effectively. 2012). In clinical practice, following cycle 1, patients have been instructed to drink 8 cups of water prior Patient Management to each dose of carfilzomib in order to prevent or Many of the more frequently reported AEs reduce fatigue as well as to reduce the risk of other such as fatigue, dyspnea, and infections can be potential AEs, including renal toxicity and tumor alleviated with proper prophylactic measures, lysis syndrome. It is, however, important to main- including hydration, dexamethasone, and antiviral/ tain homeostatic fluid balance; some patients may antibacterials (Table 3). Fatigue, which is commonly require a reduction in hydration or the addition of observed following carfilzomib use, was the most diuretics if they have signs or symptoms of fluid common treatment-emergent AE observed in the overload, including weight gain. It is also important integrated safety analysis of several phase II clinical to note that shortness of breath can be related to trials (Siegel et al., 2013). Dyspnea has been observed fluid retention. If hydration is needed post cycle 1 following carfilzomib treatment, both as part of flu- it can be reduced as necessary. Patients at high risk like infusion reactions (observed in early phase I for fluid overload (e.g., those with preexisting con- studies [Alsina et al., 2012]) including fever, rigors, gestive heart failure [CHF]) should be instructed and chills, and at other times during treatment. Anti- to monitor their weight frequently after the first viral prophylaxis was used in the clinical trials to predose and report weight gains of 3 to 5 pounds above vent viral infections in patients with MM, who typi- baseline to the clinical team. cally have myelosuppression that can be attributed Based on data from early clinical trials, to their disease as well as their course of treatment administration of very low-dose dexamethasone (Dimopoulos & Terpos, 2010; Mateos, 2010). (4 mg) prior to carfilzomib in cycles 1 and 2 is

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Table 3. Carfilzomib Administration: Recommended Prophylactic Measures

Prophylaxis Instruction Purpose Hydration Instruct the patient to drink 8 cups of water per Prevention of fatigue day during dosing Reduction in risk of renal toxicity and tumor lysis syndrome Administer 250–500 mL IV normal saline predose and again postdose as needed Dexamethasone Administer 4 mg orally or IV prior to all doses Prevention/alleviation of flu-like (infusion- of carfilzomib during cycle 1 and prior to all related) symptoms carfilzomib doses during the first cycle of dose escalation to 27 mg/m2 Antivirals Administer valacyclovir or acyclovir Particularly important in patients with a history of herpesvirus infections Antibacterials Administer moxifloxacin, levofloxacin, Prevention of infections related to cotrimoxazole, or ciprofloxacin immunosuppression, especially important for patients at risk of certain infections, including urinary tract infections and pneumonia recommended to decrease the potential occurrence Antiviral prophylaxis (e.g., valacyclovir, and severity of flu-like infusion-related symptoms, acyclovir) is recommended for patients who including dyspnea. In clinical practice, symptoms have a history of herpes zoster infections to watch for in the first 24 to 48 hours after each (Onyx Pharmaceuticals, 2012). In the clinic, dose include fever, chills, myalgia, facial swelling or antiviral prophylaxis is often administered to all flushing, vomiting, weakness, shortness of breath, patients, and antibacterial prophylaxis should hypotension, and possible chest tightness (Table 4). be considered for patients at risk of urinary tract Dexamethasone should be reintroduced if symptoms infections, pneumonia, and other infections. develop or reappear in subsequent cycles. It is important for patients to be educated Managing Common Adverse Events about the symptoms to watch out for. Additionally, In the four phase II clinical trials that caregivers should monitor the patient while he or she investigated carfilzomib, hematologic AEs is answering a question to determine if they can speak related to myelosuppression were common but without experiencing shortness of breath, which infrequently dose limiting (Nooka et al., 2012). In may occur after dosing. Shortness of breath at rest the 526 patients included in the phase II trials, should also be closely monitored. The patient should ≥ grade 3 thrombocytopenia and neutropenia be instructed to inform their health-care provider were reported in 23.4% and 10.3% of patients, immediately if he or she experiences breathing respectively. Dosing guidelines recommend difficulties so that any respiratory side effects can be that the carfilzomib dose be withheld for grade managed appropriately, which may in turn decrease 4 thrombocytopenia or ≥ grade 3 neutropenia the likelihood of dose interruptions. (Onyx Pharmaceuticals, 2012). Due to the nature of MM, thrombocytopenia is commonly seen in the clinic but is generally mild; discontinuation of therapy due to Table 4. Signs and Symptoms of Flu-Like Infusion-Related Reactions thrombocytopenia is low. Approximately a third of patients have > 50% plasmacytosis in their bone Symptoms to watch for in the first 24 to 48 hours: marrow at baseline, which leads to a reduction • Fever • Vomiting in patients’ platelet count prior to initiating • Chills • Shortness of breath and • Weakness chest tightness carfilzomib. Platelet counts typically decrease • Syncope • Angina during the dosing cycle and return to baseline prior • Myalgia, arthralgia • Hypotension to the next cycle. Thrombocytopenia is generally • Facial swelling and flushing managed first with dose reduction and then with platelet transfusions if the platelet count falls

J Adv Pract Oncol 26 AdvancedPractitioner.com SIDE EFFECT PROFILE OF CARFILZOMIB REVIEW below 25,000/μL. The carfilzomib dose should that may require magnesium and potassium be held for grade 4 thrombocytopenia until the supplementation occur in some patients during platelet count surpasses 25,000/μL. It is helpful the first cycle as well as throughout treatment. to educate patients on the signs and symptoms The imbalances are generally low grade and easily of thrombocytopenia: unexpected bruising, managed with oral supplements or increased petechiae, bleeding from the nose or gums, severe dietary intake. There may be an occasional need headaches, dizziness, and increased fatigue. for IV replacement with severe depletion. It is Grade 3 neutropenia is observed and common- recommended that chemistry panels be checked ly treated with growth factors including filgrastim at least once per cycle, with increased frequency (Neupogen), 300 or 480 μg subcutaneously (SC) in the first two cycles depending on the individual for 1 to 3 days followed by a complete blood count patient. within a week, or pegfilgrastim (Neulasta) 6 mg SC per cycle. The carfilzomib dose is held for an Consideration of Potential Adverse Events absolute neutrophil count < 1000/μL; generally It is important to comment on the AEs that patients are given growth factors and the carfilzo- occurred infrequently during the four phase II mib dose is delayed for 1 to 2 days. clinical trials but can potentially be serious none- Anemia is usually grade 1 or 2 and managed theless. Many of these AEs occur because of with growth factors such as epoetin alfa comorbidities that are observed in patients with (Procrit) 40,000 units SC weekly for hemoglobin MM: cardiac, renal, and hepatic AEs that can be ≤ 10 g/dL or darbepoetin alfa (Aranesp) 300 exacerbated upon treatment. μg SC every 2 weeks or 500 μg each month for Cardiac AEs have the potential to be serious; hemoglobin ≤ 10 mg/dL. Transfusions are rarely therefore, it is imperative to identify patients required for asymptomatic grade 1/2 anemia, and with confounding cardiac risk factors prior to although growth factors can lead to side effects, initiating carfilzomib treatment. The integrated the benefits of using them generally outweigh the safety analysis of the phase II studies, from risks. Anemia ≥ grade 3 (defined as hemoglobin < which patients with New York Heart Association 8 g/dL, < 4.9 mmol/L [National Cancer Institute, Class III-IV heart failure or recent myocardial 2010]) typically necessitates transfusions and infarction/unstable angina were excluded, sometimes requires dose interruptions and/or showed that > 70% of patients had a medical modifications. Rather than hold treatment because history of a cardiac event and 70% had cardiac of anemia, carfilzomib can be administered risk factors at baseline, including hypertension, followed by transfusion of packed cells as needed diabetes, hyperlipidemia, coronary artery disease, for hemoglobin < 8 mg/dL. and CHF (Lonial et al., 2012). Overall, a dose Gastrointestinal AEs including nausea, reduction due to a cardiac AE was required in 6 diarrhea, vomiting, and constipation were common patients (1.1%); 23 patients (4.4%) discontinued in phase II studies; however, they were rarely treatment due to a cardiac AE, including CHF dose limiting and rarely resulted in treatment (1.7%), arrhythmia (1.1%), and ischemic heart discontinuation (Onyx Pharmaceuticals, 2012; disease (1.0%; Lonial et al., 2012). Siegel et al., 2013). In clinical practice, these AEs Renal dysfunction is common in patients with are less worrisome as their frequency and severity MM, and although a majority of the patients in the vary significantly from patient to patient. Nausea phase II carfilzomib studies had renal dysfunction is generally mild in severity and very manageable. at baseline, transient worsening of renal function Premedicating with antinausea medication is was reported in 6% of patients. Nontransient suggested including oral ondansetron 8 mg, 30 worsening of renal function was reported in 7% minutes prior to carfilzomib treatment. The of patients (Harvey et al., 2012). Serious hepatic majority of patients do not typically require disorders in the phase II trials were rare (Siegel additional nausea medication. et al., 2013). Hypomagnesemia and hypokalemia were In clinical practice, because of the presence observed in the four phase II studies and were of cardiac risk factors in many patients with RR mainly grades 1 or 2 (Onyx Pharmaceuticals, MM prior to initiation of carfilzomib therapy, it is 2012). In the clinic, electrolyte imbalances important to be aware of individual symptoms and

AdvancedPractitioner.com 27 Vol 4 . No 6 . Suppl 1 . Nov/Dec 2013 REVIEW McBRIDE and SAMUEL concomitant medications and to manage them CONCLUDING REMARKS appropriately. In addition, a patient with cardiac There are certain considerations that are risk factors should be cleared by a cardiologist important in the management of patients with prior to treatment. Medication adjustment may be MM treated with carfilzomib, and a recommended required during carfilzomib treatment to manage checklist to aid in patient care is provided in the blood pressure in hypertensive patients. For patients Figure. Knowledge of the possible AEs associated with CHF, baseline and repeat echocardiograms with carfilzomib and the suggested guidelines for may be necessary, taking note of the ejection fraction patient management prior to, during, and after as well as any signs of pulmonary hypertension. treatment will help to prevent complications Patients with cardiac risk factors need to be closely and ensure that prophylactic measures are monitored for fluid overload, which is most easily implemented to reduce the frequency and severity done by monitoring weight. of side effects. It is important to educate the While renal impairment is not typically patient on possible side effects and precautions observed in response to carfilzomib treatment and to explain the actions to be taken. Establishing in clinical practice, it is important to recognize a baseline profile and monitoring the patient that small, typically transient increases in serum closely throughout the course of treatment will creatinine are often observed between the two help to personalize treatment while minimizing consecutive doses. The increases are easily discomfort and AEs. managed with adequate oral and IV hydration. Finally, the care team should work together, Dose reduction is not normally required in sharing patient information and encouraging the patients with renal dysfunction, including patient to communicate any changes or side effects patients on dialysis. Similar to renal impairment, they experience. The overall treatment goal should hepatic impairment is not a significant issue be to maximize the efficacy of carfilzomib while in the clinic, although occasional elevations in minimizing AEs and discomfort in the patient. transaminases are observed. In the event that Being aware of the clinical practice experience hepatic enzymes are elevated, a review of the with carfilzomib presented here should help APs patient’s concomitant medications is suggested. to attain that goal. The carfilzomib dose can be reduced if necessary. Another AE of importance to patients with ACKNOWLEDGMENT MM is PN, which is related either to the disease The authors would like to thank Melissa Kirk, or to treatment and is frequently observed in PhD (Fishawack Communications), for medical patients with RR MM (Mohty et al., 2010). writing and editorial assistance, which was Peripheral neuropathy was not frequently supported by Onyx Pharmaceuticals, Inc. reported during the four phase II clinical trials of carfilzomib even though most patients on study DISCLOSURE (71.9%) entered with a baseline of PN grade 1 Ms. McBride has received payment as a or 2. Notably, newly developed PN occurred member of the Onyx Speakers Bureau and infrequently, and all reported cases of PN were reimbursement for travel, accommodations, generally ≤ grade 2 and rarely resulted in dose and meeting expenses from L&M Healthcare modifications or discontinuations (Martin et al., Communications. Ms. Samuel has received an 2012). As in the clinical trial data summary, PN honorarium as a member of the Carfilzomib is rarely observed in the clinic. Advisory Board. References appear on page 30 ☛

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Recommended Carfilzomib Care Checklist

Prior to Administration  Perform a thorough history and physical examination  Obtain records of past echocardiography or pulmonary function tests  Obtain current medication list  Query patient or caregiver regarding side effects from previous treatments  Note which medications were used/helpful  Explain the importance of hydration (8 cups of water/day) and prophylactic dexamethasone as well as any antivirals/ antibiotics necessary  Explain flu-like infusion-related reaction symptoms and timing  Explain precautions to females of childbearing age  Explain patient responsibilities, including:  Report early signs of shortness of breath  Stay well hydrated to avoid dehydration  Inform the doctor before starting new medications  Monitor weight  Give IV hydration for the first cycle and make sure the patient is well hydrated for all cycles  Administer dexamethasone premedication for the first cycle and as needed for later cycles  Check weight prior to treatment

During Administration  Monitor for fluid overload

Post Administration  Monitor for infusion-related reactions (e.g., flu-like symptoms)  Monitor for injection site-related reactions (e.g., phlebitis)  Monitor for fluid overload  Monitor vital signs for 30 minutes after infusion for changes in blood pressure, temperature, and pulse

Figure. Recommended carfilzomib patient care checklist.

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