Carfilzomib, cyclophosphamide, and dexamethasone (KCd) for the treatment of triple-class relapsed/refractory multiple myeloma (RRMM).

BACKGROUND: Multiple myeloma (MM) is an incurable hematologic malignancy, and outcomes remain poor for patients with triple-class relapsed/refractory MM (RRMM). Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes of the KCd on triple-class RRMM patients at our institution. PATIENTS AND METHODS: Twenty-three patients with triple-class RRMM treated with KCd between June 2017 and October 2020 were included in our analysis. The regimen KCd consisted of 28 days cycles of carfilzomib 20/36 mg/m2 IV on days 1, 2, 8, 9, 15, and 16, cyclophosphamide 300 mg/m2 IV weekly, and dexamethasone (20-40) mg orally weekly. RESULTS: Patients received a median of 6 (3-10) prior regimens. The median number of cycles administered was 4 (1-11) cycles. Overall response rate was 52%, 6 patients (26%) achieved very good partial response (VGPR), 6 patients (26%) achieved partial response (PR), and 5 patients (22%) achieved stable disease (SD). Progression-free survival (PFS) and Overall-survival (OS) were 4 and 11.9 months, respectively. There was no reported treatment-related mortality. The most common grade ≥3 adverse events were neutropenia (26%), thrombocytopenia (56.5%), and anemia (56.5%). CONCLUSIONS: KCd showed clinically meaningful efficacy and manageable safety profile in patients with triple-class RRMM in real-world.

Bilateral Cystoid Macular Edema with Zanubrutinib Therapy: A Case Report.

We present a patient with recurrent mantle cell lymphoma (MCL) who was treated with zanubrutinib, a Bruton's tyrosine kinase inhibitor. He subsequently developed bilateral cystoid macular edema (CME) in both eyes. This is the first report of CME in a patient with MCL who was treated with zanubrutinib. CME was refractory to topical corticosteroid therapy, but sub-Tenon's steroid injections and holding off zanubrutinib managed to decrease the CME. Treatment managed to prevent further vision loss but did not restore lost vision. The prompt ophthalmic exam is recommended for patients on zanubrutinib with decreased vision.

Uveo-meningeal syndrome secondary to Herpes Simplex Virus related acute retinal necrosis.

PURPOSE: To present a rare case of uveo-meningeal syndrome secondary to herpes simplex virus (HSV-1) in a patient with acute retinal necrosis. OBSERVATIONS: A 49-year-old female with a past medical history of herpes simplex encephalitis 18 years prior presented with a 3-day history of right sided headache and decreased vision of the right eye. Her visual acuity was 20/30 in the right eye and 20/20 in the left eye. Clinical examination revealed right relative afferent pupillary defect, panuveitis, and retinal necrosis. Examination of the left eye was unremarkable. Cerebral spinal fluid (CSF) analysis by polymerase chain reaction (PCR) was negative for herpes simplex virus 1 (HSV-1) but did reveal pleocytosis consistent with meningitis. The patient was admitted and empirically treated with intravenous acyclovir (10 mg/kg every 8 hours) and systemic steroids. Topical steroids and cycloplegia were also started. Magnetic resonance imaging revealed no leptomeningeal, pachymeningeal, or parenchymal enhancement. Systemic autoimmune and infectious workup were unremarkable. Based on clinical exam findings and negative PCR results, an anterior chamber tap was performed with aqueous fluid PCR testing which revealed 71,000 copies of HSV-1. A repeat lumbar puncture was performed on day three of admission and revealed a decrease in pleocytosis after initiation of acyclovir therapy and remained negative for HSV on PCR testing. She was discharged home on intravenous acyclovir, topical steroids, and topical cycloplegics. Her retinal necrotic lesions continued to regress and her headaches continued to improve. CONCLUSIONS AND IMPORTANCE: Uveo-meningeal syndromes are a rare clinical entity that involve the uvea, retina, and meninges. This case highlights the importance of aqueous fluid PCR testing despite negative CSF PCR, as it may hasten treatment with antiviral therapies to preserve vision and limit neurologic sequelae.

Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice.

Elucidating the underlying molecular mechanisms regulating fear and extinction learning may offer insights that can lead to novel treatments for debilitating anxiety and trauma-related disorders including posttraumatic stress disorder. The endocannabinoid (eCB) system is a retrograde inhibitory signaling pathway involved in regulating central responses to stress. The eCB 2-arachidonoylglycerol (2-AG) has recently been proposed to serve as a homeostatic signal mitigating adverse effects of stress exposure, however, less well understood is 2-AG's role in fear learning and fear extinction. In this study, we have sought to explore 2-AG's role in fear conditioning and fear extinction by disrupting 2-AG synthesis utilizing the DAGL inhibitor (DO34) and DAGLα knock-out mice (DAGLα-/-). We found that DAGLα-/- mice, and male and female C57B6/J mice treated with DO34, exhibited impairment in extinction learning in an auditory cue fear-conditioning paradigm. DO34 did not increase unconditioned freezing. Interestingly, inhibition of fatty-acid amide hydrolase was not able to restore normal fear extinction in DO34-treated mice suggesting increased Anandamide cannot compensate for deficient 2-AG signaling in the regulation of fear extinction. Moreover, augmentation of CB1R signaling with tetrahydrocannabinol also failed to restore normal fear extinction in DO34-treated mice. Overall, these data support the hypothesis that DAGLα plays an important role in fear extinction learning. Although genetic and pharmacological disruption of DAGL activity causes widespread lipidomic remodeling, these data combined with previous studies putatively suggest that deficient 2-AG signaling could be a susceptibility endophenotype for the development of trauma-related psychiatric disorders.