Transition from Intravenous to Subcutaneous Daratumumab Formulation in Clinical Practice.

INTRODUCTION: Daratumumab is an anti-CD38 monoclonal antibody widely used for treating patients with newly diagnosed or relapsed/refractory multiple myeloma. The subcutaneous formulation of daratumumab was developed with the purpose of minimizing the treatment burden (to patients and health care system) associated with intravenous daratumumab. Given its recent approval, there is a knowledge gap regarding the best practices that should be instituted for safe administration of subcutaneous daratumumab. METHODS: A retrospective chart review was performed from August 2020 until November 2020 to identify patients either switched to or treated upfront (daratumumab naive) with any subcutaneous daratumumab-based treatment regimen. All patients received appropriate premedications per institutional standards of care. The study end points were to report real-world data regarding administration-related reaction rates (at or following discharge from infusion center), as well as compare their incidence rates to those noted in the COLUMBA study (historical cohort). RESULTS: The study included 58 patients, of whom 38% (n = 22) were daratumumab naive. The majority (84%, n = 49) received subcutaneous daratumumab in combination with various antimyeloma regimens. There were no cases of administration-related reactions at infusion center or after discharge irrespective of previous exposure to intravenous daratumumab. None of the patients included herein required rescue home medications or visited the emergency department within 24 to 48 hours after subcutaneous daratumumab administration. These translated into a significant difference in incidence of administration-related reactions compared with historical cohort (0% vs. 13%, P = .003). CONCLUSION: Subcutaneous daratumumab was extremely well tolerated and could be safely administered without need for monitoring or rescue home medications.

Alternative Clinical Indications of Botulinum Toxin.

Botulinum toxin type A (BoNTA) is a powerful neurotoxin that inhibits acetylcholine release from presynaptic vesicles. The potency and safety profile of BoNTA grant the toxin vast therapeutic potential. It has been used off-label for a variety of dermatologic conditions. This review aims to analyze published literature regarding the benefits and risks of the off-label use of BoNTA beyond facial lines, including eccrine hidrocystomas, enlarged pores, keloids and hypertrophic scars, hidradenitis suppurativa, hyperhidrosis, masseter muscle hypertrophy, and salivary gland hypertrophy, among others. A MEDLINE search from January 2000 to December 2019 was conducted on the off-label uses of botulinum toxin in dermatology.

Differentiating Nonpermanent Injectable Fillers: Prevention and Treatment of Filler Complications.

Though the incidence of complications and adverse events with dermatological fillers is inherently low, practitioners should be well versed in both prevention of filler complications and the treatment algorithms for addressing "granulomas," nodules, infection, and vascular compromise. Appropriate preventative measures, coupled with timely and effective treatment, are critically important for patient safety and satisfaction. In addition to the preventive measures and treatment algorithms outlined here, the authors emphasize that the broad classification and treatment of nodules as "granulomas" is likely to lead to ineffective treatment, or worse, unnecessary exposure to incorrect treatment. In practice, nodules are classified and treated based on clinical manifestation (eg, late vs early or noninflammatory vs inflammatory) rather than on histology. Indeed, classification of a nodule as a granuloma requires a histological examination, rarely available (or necessary) in clinical practice to guide treatment. Thus, the apparent inflammatory nature of the nodule and the time of onset should drive treatment approach. The treatment algorithms presented here are based on these clinically meaningful parameters.

Subcutaneous Rituximab for the Treatment of B-Cell Hematologic Malignancies: A Review of the Scientific Rationale and Clinical Development.

Rituximab (MabThera®/Rituxan®), a chimeric murine/human monoclonal antibody that binds specifically to the transmembrane antigen CD20, was the first therapeutic antibody to enter clinical practice for the treatment of cancer. As monotherapy and in combination with chemotherapy, rituximab has been shown to prolong progression-free survival and, in some indications overall survival, in patients with various B-cell malignancies, while having a well-established and manageable safety profile and a wide therapeutic window. As a result, rituximab is considered to have revolutionized treatment practices for patients with B-cell malignancies. A subcutaneous (SC) formulation of rituximab has been developed, comprising the same monoclonal antibody as the originally marketed formulation [rituximab concentrate for solution for intravenous (IV) infusion], and has undergone a detailed, sequential clinical development program. This program demonstrated that, at fixed doses, rituximab SC achieves non-inferior serum trough concentrations in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia, with comparable efficacy and safety relative to the IV formulation. The added benefit of rituximab SC was demonstrated in dedicated studies showing that rituximab SC allows for simplified and shortened drug preparation and administration times resulting in a reduced treatment burden for patients as well as improved resource utilization (efficiency) at the treatment facility. The improved efficiency of delivering rituximab's benefit to patients may broaden patient access to rituximab therapy in areas with low levels of healthcare resources, including IV-chair capacity constraints. This article is a companion paper to G. Salles, et al., which is also published in this issue. FUNDING: F. Hoffmann-La Roche Ltd.

New High Dose Pulsed Hyaluronidase Protocol for Hyaluronic Acid Filler Vascular Adverse Events.

The purpose of this article is to update the changes to the author's protocols used to manage acute filler related vascular events from those previously published in this journal. For lack of a better term, this new protocol has been called the High Dose Pulsed Hyaluronidase (HDPH) protocol for vascular embolic events with hyaluronic acid (HA) fillers. The initial protocol used involved many different modalities of treatment. The current protocol is exceedingly simple and involves solely the use of hyaluronidase in repeated high doses. Despite the simplicity of the treatment, it has proven itself to be very successful over the past two years of clinical use. There has been no partial or complete skin loss associated with this protocol since its implementation if the protocol was implemented within 2 days of the ischemic event onset. The protocol involves diagnosis and repeated administration of relatively high doses hyaluronidase (HYAL) into the ischemic tissue repeated hourly until resolution (as detected clinically through capillary refill, skin color, and absence of pain). The dosage of HYAL varies as the amount of ischemic tissue, consistent with the new underlying hypothesis that we must flood the occluded vessels with a sufficient concentration of HYAL for a sufficient period of time in order to dissolve the HA obstruction to the point where the products of hydrolysis can pass through the capillary beds. Although vascular embolic events are rare, it is important to note that the face has higher risk and lower risk areas for filler treatment, but there are no "zero risk" areas with respect to filler treatments. Even with good anatomic knowledge and correct technique, there is still some nonzero risk of vascular embolic events (including highly skilled, experienced injectors). However, with careful low pressure, low volume injection technique, and adequate preparation for treatment of acute vascular events, the risk is quite manageable and the vast majority of adverse events are very treatable with an excellent prognosis, with a few exceptions. This new protocol offers excellent results, but requires further research to determine optimal parameters for various HA fillers.

Subcutaneous heparin for prophylaxis of venous thromboembolism in deep brain stimulation surgery: evidence from a decision analysis.

OBJECTIVE: The addition of subcutaneous heparin (SQH) to mechanical prophylaxis for venous thromboembolism (VTE) involves a balance between the benefit of greater protection from VTE and the added risk of intracranial hemorrhage. There is evidence that the hemorrhage risk outweighs the benefits for patients undergoing craniotomy. We investigated the safety of SQH in patients undergoing deep brain stimulation (DBS) surgery. METHODS: A retrospective analysis was performed of all patients with movement disorders (n = 254) undergoing DBS surgery at our institution from 2003 to 2007. Before September 2005, none of the patients undergoing DBS received SQH (non-SQH group) (n = 121). Thereafter, all patients were administered SQH perioperatively (SQH group) (n = 133). All patients wore graduated compression stockings and pneumatic compression boots postoperatively in bed. A postoperative brain magnetic resonance imaging scan was obtained on the day of surgery. RESULTS: Five (3.8%) of 133 SQH patients and 1 (0.8%) of 121 non-SQH patients developed asymptomatic intracranial hemorrhage. None of the SQH patients developed clinically significant VTE, whereas 3 (2.5%) non-SQH patients developed VTE (1 deep venous thrombosis, 2 pulmonary embolisms). Using a decision-analysis model, we have shown that the use of SQH plus mechanical prophylaxis together yielded outcomes at least as good as mechanical prophylaxis alone. CONCLUSION: Our findings suggest that SQH for VTE prophylaxis in patients with movement disorders undergoing DBS surgery is safe. SQH protects against VTE in this patient population and merits further investigation.