Preoperative parameters (signalment, digital radiography, urinalysis, urine microbiological culture) and novel algorithm improve prediction of canine urocystolith composition.

OBJECTIVE: To determine the accuracy of 4 preoperative parameters (signalment, urinalysis, urine microbiological culture, and digital radiography) in predicting urocystolith composition, compare accuracy between evaluators of varying clinical experience and a mobile application, and propose a novel algorithm to improve accuracy. ANIMALS: 175 client-owned dogs with quantitative analyses of urocystoliths between January 1, 2012, and July 31, 2020. METHODS: Prospective experimental study. Canine urocystolith cases were randomly presented to 6 blinded "stone evaluators" (rotating interns, radiologists, internists) in 3 rounds, each separated by 2 weeks: case data alone, case data with a urolith teaching lecture, and case data with a novel algorithm. Case data were also entered into the Minnesota Urolith Center mobile application. Prediction accuracy was determined by comparison to quantitative laboratory stone analysis results. RESULTS: Prediction accuracy of evaluators varied with experience when shown case data alone (accuracy, 57% to 82%) but improved with a teaching lecture (accuracy, 76% to 89%) and further improved with a novel algorithm (accuracy, 93% to 96%). Mixed stone compositions were the most incorrectly predicted type. Mobile application accuracy was 74%. CLINICAL RELEVANCE: Use of the 4 preoperative parameters resulted in variable accuracy of urocystolith composition predictions among evaluators. The proposed novel algorithm improves accuracy for all clinicians, surpassing accuracy of the mobile application, and may help guide patient management.

Mosunetuzumab Safety Profile in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma: Clinical Management Experience From a Pivotal Phase I/II Trial.

BACKGROUND: Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody approved in Europe and the United States for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior therapies. MATERIALS AND METHODS: We present interim safety data from the mosunetuzumab GO29781 (NCT02500407) phase I/II dose-escalation study in R/R non-Hodgkin lymphoma (NHL), focusing on FL. RESULTS: Overall, 218 patients with R/R NHL, including 90 with R/R FL, received a median of eight 21-day cycles of intravenous mosunetuzumab with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1 mg; C1D8, 2 mg; C1D15/C2D1, 60 mg; C3D1 and onwards, 30 mg). Cytokine release syndrome (CRS) was the most common adverse event (AE), occurring in 39.4% (NHL) and 44.4% (FL) of patients. Events occurred predominantly during C1 at the first loading dose; the majority were grade 1/2. CRS events were managed at the investigator's discretion with supportive care, steroids, and tocilizumab, based on protocol management guidelines. Immune effector cell-associated neurotoxicity syndrome was uncommon, reported in 0.9% (NHL) and 1.1% (FL) of patients. Neutropenia occurred in 27.5% (NHL) and 28.9% (FL) of patients (mostly grade 3/4) and could be effectively managed using granulocyte colony-stimulating factor. Tumor lysis syndrome occurred in 0.9% (NHL) and 1.1% (FL) of patients (all grade 3/4 with CRS; all resolved). CONCLUSION: Mosunetuzumab monotherapy as treatment for R/R B-cell NHL, including FL, was associated with low rates of severe AEs (including CRS) and is suitable for outpatient administration in the community setting. Adapted protocol guidance for the management of select AEs during mosunetuzumab treatment is included.

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial.

Relapsed/refractory aggressive large B cell lymphoma (LBCL) remains an area of unmet need. Here we report the primary analysis of a phase 1b/2 trial of outpatient mosunetuzumab (a CD20xCD3 T-cell-engaging bispecific antibody) plus polatuzumab vedotin (an anti-CD79B antibody-drug conjugate) in relapsed/refractory LBCL. The phase 2 component is a single arm of an ongoing multi-arm trial. The primary endpoint during dose expansion was independent review committee (IRC)-assessed best overall response rate. Secondary endpoints included investigator-assessed overall response rate, complete response, duration of response, progression-free survival and overall survival. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% confidence interval (CI): 48.8-69.0) and 45.9% (45/98; 95% CI: 35.8-56.3), respectively (median follow-up, 23.9 months). Median duration of complete was not reached (95% CI: 20.5-not estimable (NE)). Median progression-free survival was 11.4 months (95% CI: 6.2-18.7). Median overall survival was 23.3 months (95% CI: 14.8-NE). Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients. These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 .

Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma.

As part of a phase 1 or 2 study, this single-arm expansion cohort established the efficacy and safety of mosunetuzumab monotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (received ≥2 previous lines of therapy). Intravenous mosunetuzumab was administered with cycle (C) 1 step-up dosing for cytokine release syndrome (CRS) mitigation: C1 day (D) 1: 1 mg; C1D8 2 mg; C1D15 and C2D1: 60 mg; C3 + D1: 30 mg. Hospitalization was not mandatory. Patients with complete response (CR) completed treatment after C8; those with partial response or stable disease continued treatment for a total of 17 cycles. The primary end point was CR rate (best response), assessed against a historical control CR rate (20%) by independent review facility. Eighty-eight patients (73.9% de novo DLBCL; 26.1% transformed follicular lymphoma) were enrolled; all had received previous anthracycline and anti-CD20 therapy. Overall response and CR rates were 42.0% (95% confidence interval [CI], 31.6-53.1) and 23.9% (95% CI, 15.4-34.1), respectively; CR rate did not reach statistical significance vs the historical control (P = .36). Median time to first response was 1.4 months. Median progression-free survival was 3.2 months (95% CI, 2.2-5.3). The CR rate in 26 patients who received previous chimeric antigen receptor T-cell (CAR-T) therapy was 12%. CRS was one of the most common adverse events (26.1% of patients); predominantly grade 1 to 2 and primarily in C1. Four patients (4.5%) discontinued mosunetuzumab owing to adverse events. Mosunetuzumab demonstrated notable efficacy and a manageable safety profile in patients with R/R DLBCL, including those previously treated with CAR-Ts. This trial was registered at www.clinicaltrials.gov as #NCT02500407.

Suspected primary pure red cell aplasia in a 4-month-old intact male mixed breed Bernese mountain dog.

A 4-month-old, 31-kg intact male mixed-breed Bernese mountain dog was presented for evaluation of severe non-regenerative anemia after several days of lethargy, inappetence and pale mucous membranes. Bone marrow evaluation and complete response to immunosuppressive therapy were suggestive of primary pure red cell aplasia (PRCA). Primary PRCA is a rare immune-mediated non-regenerative anemia that is overrepresented in middle-aged to older spayed female dogs and has not previously been described in an intact male puppy.

Aplasie primaire pure des globules rouges suspectée chez un bouvier bernois mixte mâle intact âgé de 4 mois. Un bouvier bernois mixte mâle intact âgé de 4 mois et pesant 31 kg a été présenté pour l'évaluation d'une anémie grave non régénérative après plusieurs jours de léthargie, d'inappétence et de muqueuses pâles. L'évaluation de la moelle osseuse et la réponse complète au traitement immunosuppresseur suggéraient une aplasie primaire pure des globules rouges (PRCA). L'érythroblastopénie primaire est une anémie non régénérative à médiation immunitaire rare qui est surreprésentée chez les chiennes stérilisées d'âge moyen à plus âgées et qui n'a pas été précédemment décrite chez un chiot mâle intact.(Traduit par Dr Serge Messier).