ABSTRACT
PURPOSE: ABBV-838 is an antibody-drug conjugate targeting a unique epitope of CD2 subset 1, a cell-surface glycoprotein expressed on multiple myeloma cells. This phase I/Ib first-in-human, dose-escalation study (trial registration ID: NCT02462525) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-838 in patients with relapsed and refractory multiple myeloma (RRMM). PATIENTS AND METHODS: Eligible patients (≥18 years) received ABBV-838 (3+3 design) intravenously starting from 0.6 mg/kg up to 6.0 mg/kg for 3-week dosing intervals (Q3W). Patients could continue ABBV-838 for up to 24 months. Assessment of alternate dosing intervals (Q1W and Q2W) was conducted in parallel. RESULTS: As of March 2017, 75 patients received at least one dose of ABBV-838. The most common any-grade treatment-emergent adverse events (TEAE) were neutropenia and anemia (28.0% each), fatigue (26.7%), and nausea (25.3%). Grade 3/4/5 TEAEs were reported in 73.3% of patients across all treatment groups; most common were neutropenia (20.0%), anemia (18.7%), and leukopenia (13.3%). Grade 3/4/5 ABBV-838-related TEAEs were reported by 40.0% of patients across all treatment groups. Overall, 4.0% of patients experienced TEAEs leading to death, none ABBV-838 related. The MTD was not reached; the selected recommended dose for the expansion cohort was 5.0 mg/kg Q3W. Pharmacokinetic analysis showed that exposure was approximately dose proportional. The overall response rate was 10.7%; very good partial responses and partial responses were achieved by 2 (2.7%) and 6 (8.0%) patients, respectively. CONCLUSIONS: These results demonstrate that ABBV-838 is safe and well-tolerated in patients with RRMM with a very limited efficacy.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunoconjugates/therapeutic use , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Signaling Lymphocytic Activation Molecule Family/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/pharmacokinetics , Cohort Studies , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Humans , Immunoconjugates/pharmacokinetics , Male , Middle Aged , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Prognosis , Salvage Therapy , Signaling Lymphocytic Activation Molecule Family/immunology , Tissue DistributionABSTRACT
Squamous cell carcinoma arising in a dentigerous cyst is a rare lesion with distinct histopathology and stringent criteria for diagnosis.(1,2) During the past century, <60 cases have been reported.(3) Of the previously documented cases, all have occurred in adults. We present the case of a squamous cell carcinoma arising in a dentigerous cyst in a 16-month-old girl. This case poses interesting questions regarding the pathophysiology of these tumors and highlights the importance of maintaining a high index of suspicion regardless of age when evaluating cystic lesions of the mandible and maxilla.
Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/etiology , Dentigerous Cyst/complications , Dentigerous Cyst/diagnostic imaging , Mandibular Neoplasms/diagnostic imaging , Mandibular Neoplasms/etiology , Carcinoma, Squamous Cell/pathology , Dentigerous Cyst/pathology , Female , Humans , Infant , Mandibular Neoplasms/pathology , RadiographyABSTRACT
An elderly patient with a history of chronic migraine was hospitalized with systolic hypertension and significant mental status changes, including increasing confusion, combative behavior, and remarkably detailed auditory hallucinations of several weeks' duration. Daily increased consumption of a product containing ergotamine 1 mg and caffeine 100 mg coincided with both onset and increasing severity of symptoms. To our knowledge, this is the first case reported in the contemporary literature of severe mental status changes and hallucination possibly due to ergotamine-caffeine.
