PORT (OP-109): Phase 2, Randomized, Pharmacokinetic (PK), Cross-over Study of Peripheral Vs Central Intravenous Administration of Melflufen in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Introduction: Melphalan flufenamide (melflufen) is a peptide-drug conjugate with unique PK properties that rapidly penetrates cells, where it is metabolized to melphalan either directly or through an intermediate metabolite, desethyl-melflufen. Melflufen has only been administered via central venous catheter (CVC); however, peripheral venous catheter (PVC) administration may be preferred by patients if safety and tolerability are acceptable. The ongoing PORT study (NCT04412707) aims to compare the PK of melphalan after central and peripheral administration of melflufen, and to assess the local tolerability of peripheral administration of melflufen. The overall efficacy and safety of melflufen in patients with RRMM will also be evaluated. Methods: Patients (following ≥2 lines of prior therapy) were randomized (1:1) to melflufen 40 mg (administered on Day 1 of each cycle; combined with weekly oral dexamethasone 40 mg [20 mg for patients aged ≥75 years] on Days 1, 8, 15, and 22) either via PVC in Cycle 1 then CVC in Cycle 2 (Arm A) or via CVC in Cycle 1 and then PVC in Cycle 2 (Arm B). From Cycle 2 (Arm A) or Cycle 3 (Arm B) onward, patients received melflufen via CVC. PK sampling was performed frequently during and after the 30-minute melflufen infusion. Primary endpoints were maximum observed concentration (C max), area under the concentration-time profile from start of infusion to both last measurable concentration (AUC 0-t) and infinity (AUC 0-inf) for melphalan, and frequency and severity of PVC-related local infusion-site reactions. Secondary endpoints included PK variables for melflufen and desethyl-melflufen and general safety and tolerability. PK parameters after CVC and PVC administration were compared using bioequivalence methods. Patient satisfaction and nurse convenience after CVC and PVC administration (Day 1 of Cycles 1 and 2) were also explored. Results: At data cutoff (June 2, 2021), 27 patients had received melflufen (median age 67 years; 48.1% male), of whom 19 patients received at least 2 doses and were evaluable for PK analysis. Melphalan C max, AUC 0-t, and AUC 0-inf met bioequivalence criteria for CVC and PVC administration, as demonstrated by a 90% confidence interval (CI) for the ratio of means within 80-125%. Geometric mean melphalan concentration over time by CVC vs PVC is shown in Figure 1. For melflufen, the ratio of means was 107-117% for the PK parameters, with all upper 90% CIs above 125%. For desethyl-melflufen, AUC 0-t and AUC 0-inf met bioequivalence criteria and the 90% CI for C max was marginally above the upper limit (127%). Melflufen disappeared rapidly from plasma after the end of infusion, with an average half-life of 5-7 minutes. Melphalan C max was observed on average 7-9 minutes after the end of melflufen infusion for both routes of administration, which reflects the delay in distribution of melphalan from tissues to plasma. Furthermore, there were no local or systemic tolerability issues reported, and patient-reported satisfaction and nurse-reported convenience were comparable for CVC and PVC melflufen administration. The overall melflufen safety profile was in line with previous studies. Conclusions: Systemic melphalan exposure is similar after melflufen PVC and CVC administration. Differences between PVC- and CVC-related PK parameters for melflufen and desethyl-melflufen are considered to have no clinical consequences because their plasma-exposure duration is short. There were no local reactions after melflufen PVC administration. Figure 1 Figure 1. Disclosures Minarik: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Micheva: Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Andzhelini Farma: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Usenko: AbbVie: Consultancy, Honoraria, Other: Clinical Trials Investigator; Janssen: Consultancy, Honoraria, Other: Clinical Trials Investigator; Pfizer: Consultancy, Honoraria; Acerta: Other: Clinical Trials Investigator; Ascentage: Other: Clinical Trials Investigator; Celgene: Other: Clinical Trials Investigator; Il-Yang: Other: Clinical Trials Investigator; Karyopharm: Other: Clinical Trials Investigator; Oncopeptides: Other: Clinical Trials Investigator; Rigel: Other: Clinical Trials Investigator; Takeda: Other: Clinical Trials Investigator; UCB: Other: Clinical Trials Investigator. Mikala: Takeda: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Janssen: Honoraria. Thuresson: Oncopeptides AB: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Jerling: Oncopeptides: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Xie: Oncopeptides: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.

Nurses’ knowledge and experience related to short peripheral venous catheter extravasation

Background: The majority of hospitalized patients receive a Peripheral Venous Catheter (PVC) in the course of their treatment. Extravasation injury is a serious complication of intravenous treatment. Objective: This cross-sectional survey designed study aims to investigate nurses’ knowledge and experience related to short peripheral venous catheter extravasation. Method: The study sample included 145 nurses working in a university hospital in the west of Turkey. A questionnaire developed in accordance with the literature was used for data collection. The data were assessed by frequency and proportions. Results: Of the nurses included in this study, 26.2% reported they had experienced extravasation injury in a patient; 74.5% said they had received no instruction in the management of extravasation during their in-service training program; and 85.5% stated they did not keep a record of extravasation. 89.7% of the nurses reported infused medications as a cause of extravasation, and 81.4% reported catheter sites as a cause. Among the medications reported by the nurses as causing extravasation: 89.7% reported contrast agents; 84.8% TPN solutions; 71.0% cytotoxic agents; and 65.1% mannitol. The symptoms of extravasation reported by nurses included: swelling (97.9%), redness (97.2%), pain (92.4%), rise in temperature (65.5%), and ulceration (60.0%). In responding to the occurrence of extravasation, interventions reported by the nurses included: stopping the flow of fluid (98.6%), elevation (89.7%), cold application (76.6%), and aspiration of drug (40.7%). Conclusion: Based on these results, it is recommended that guidelines are developed for the management of extravasation, that periodic in-service training programs are provided and that observational studies are carried out into the administration of vesicant drugs.

First human case of catheter-related blood stream infection caused by Staphylococcus schleiferi subspecies coagulans: a case report and literature review

Background Staphylococcus schleiferi is a gram-positive pathogenic coccus which causes canine skin and ear infections. Only four cases of human infection caused by Staphylococcus schleiferi subspecies coagulans have been reported. Herein, we present the first case of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. Case presentation A 62-year-old Japanese man was admitted to our hospital for examination of sigmoid colon tumor. During hospitalization, he had fever, shaking chills, and swelling at the peripheral venous catheter insertion site. Two sets of blood cultures were positive for S. schleiferi subspecies coagulans which was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S ribosomal RNA sequencing and the coagulase test. The patient was successfully treated without relapse. Conclusion To our knowledge, this is the first report of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. S. schleiferi subsp. coagulans can be pathogenic in humans, and MALDI-TOF MS can contribute to accurate identification of S. schleiferi subspecies coagulans.

Case report: risk of skin necrosis related to injectable vancomycin in critically ill newborn infants

Background Vancomycin is commonly used as part of empiric antibiotic therapy in the preterm infants who develop signs and symptoms of infection. Although skin necrosis has been noted to occur following injection of vancomycin into a peripheral vein in an adult patient, this complication has not been previously described in a preterm infant. Case presentation We report the case of a very low birthweight male infant born at 30 weeks gestational age who developed skin necrosis, most likely as a complication of vancomycin administration via a peripheral venous catheter. The immature skin and endothelial cells of this preterm infant may have increased the risk of drugs related venous and skin toxicity. In this case, assumption of a cumulative toxicity with other drugs administered concomitantly via the same catheter can’t be excluded. Conclusions To prevent the risk of skin damage, we advocate that in newborn infants, the administration of vancomycin should be limited to a concentration of < 2.5 mg/mL via a peripheral intravenous catheter if a central venous catheter is not available.

A case of COVID-19 with superficial thrombophlebitis caused by an indwelling peripheral venous catheter

Background: COVID-19 is caused by SARS-CoV-2 infection, and cytokine storm and microthrombus formation affect the severity of the disease, which is often complicated by venous thrombosis due to a systemic hypercoagulable state. On the other hand, indwelling peripheral venous catheters can cause catheter-related bloodstream infections and venous thrombus formation, albeit less frequently. Case presentation: A 53-year-old man was admitted to the hospital with severe COVID-19. He had bilateral pneumonia and required ventilator management but recovered after steroid and anticoagulation. On the 26th day after onset, redness, swelling, and pain developed around the insertion site of the catheter placed in the cephalic vein of the left forearm. Vascular ultrasonography revealed a thrombus in this vein accompanied by inflammation in the surrounding tissues. Catheter-related bloodstream infection was suspected and vancomycin was administered; however, blood cultures were negative, leading to the diagnosis of non-infectious superficial thrombophlebitis. The skin findings improved after removal of the peripheral venous catheter. Conclusions: This case suggested that catheter placement in peripheral veins during COVID-19 treatment increases the risk of thrombus formation. Although anticoagulant therapy is able to control the systemic hypercoagulable state caused by COVID-19, indwelling catheters can induce a local hypercoagulable state, leading to superficial thrombophlebitis.