Résumé
In phase 1 of CC-92480- MM- 001 (NCT03374085), the recommended phase 2 dose (RP2D) of mezigdomide plus dexamethasone (MEZI-d) was selected at 1 mg once daily for 21/28 days. Here we report preliminary results from the MEZI-d dose-expansion cohort in patients with heavily pretreated RRMM. Key eligibility criteria were: RRMM;>=3 prior lines of therapy;disease progression <=60 days of last myeloma therapy;refractoriness to lenalidomide/pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody. Oral mezigdomide 1 mg was given on days 1-21 of each 28-day cycle, plus weekly dexamethasone (40 mg;20 mg if >75 years of age). Primary objective was to evaluate efficacy (overall response rate [ORR]);secondary objectives included safety/tolerability and additional efficacy assessments. Pharmacodynamics was an exploratory objective. As of 16/Sep/2022, 101 patients had received MEZI-d at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years;39.6% of patients had plasmacytomas and 37/101 patients had high-risk cytogenetics (56/101 not evaluable). Median number of prior regimens was 6 (3-15);prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%). All patients were refractory to last myeloma regimen and triple-class refractory. Median follow-up was 7.5 (0.5-21.9) months, with a median of 4 (1-20) cycles;10.0% of patients continued treatment;progressive disease was the main reason for discontinuation (60.4%). ORR was 40.6% for all patients. Whilst data are not mature yet, median PFS was 4.4 (95% CI 3.0-5.5) months and median duration of response was 7.6 (95% CI 5.4-9.5) months. ORR was 30.0% in patients with plasmacytomas (N = 40) and 50.0% in patients with prior anti-BCMA therapy (N = 30). Ninety-one (91.1%) patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). Most frequent hematologic grade 3/4 TEAEs were neutropenia (75.2%), anaemia (35.6%), and thrombocytopenia (27.7%);34.7% of patients had grade 3/4 infections, including grade 3/4 pneumonia (15.8%) and COVID-19 (7.0%). Occurrence of other grade 3/4 non-hematologic TEAEs was generally low. Due to TEAEs, 76.2% and 29.7% of patients had mezigdomide dose interruptions and reductions, respectively;90.1% of patients discontinued mezigdomide. Mezigdomide induced substrate degradation and increases in activated and proliferating T cells in patients, including those directly refractory to pomalidomide-based therapies. MEZI-d had a manageable safety profile with encouraging efficacy in patients with triple-class refractory RRMM, including patients with prior BCMA-targeted therapies. These results strongly support the continued development of mezigdomide in MM, and especially in combination.
Résumé
Alternative education (AE) settings support students with significant social–emotional and behavioral needs. Such settings often implement individualized programming;however, this presents challenges with staffing resources and training. Application of systems to address behavior on a schoolwide level could simplify training, increase staffing flexibility, and decrease use of crisis response procedures. This 2-year, descriptive case study provides an implementation example of universal behavioral supports based on a Positive Behavioral Interventions and Supports (PBIS) framework within an AE setting. Over the course of the study, a reduction in staff use of restraint and seclusion procedures was observed. Additionally, staff perceived the framework favorably. Implementation steps are described, along with differentiation of the framework to meet the needs of a heterogeneous student population within the context of the COVID-19 pandemic.
Résumé
Background: Concerns about safety and treatment interference are known barriers to COVID-19 vaccination in cancer patients. Data on safety and tolerability in this population remain scarce. One of the objectives of this study is to describe COVID-19 vaccination safety in cancer patients. Methods: Patients diagnosed with a malignancy requiring systemic treatment in the last 12 months and undergoing COVID-19 vaccination were prospectively enrolled in this single-center study. Validated questionnaires to assess vaccine-related adverse events (VRAEs) were collected;chart review identified baseline characteristics and treatments received. Descriptive statistics and logistic regressions were performed. Results: 253 questionnaires were collected from 171 patients, enrolled between May and September 2021. 130 patients were survey-eligible after the 1st dose (D1) and 185 after 2nd dose (D2). 91 questionnaires were collected after D1 (Questionnaire 1: Q1) and 162 after D2 (Questionnaire 2: Q2). Surveys couldn't be collected due to interval > 1 month between D1 / enrollment, patients' unavailability, withdrawal of study or death. Median age was 55 (24-87) and 62.8% were female. 58.5% had solid tumors, treated with chemotherapy (49%) or checkpoint inhibitors only (9.5%);19.4% malignancies were treated with targeted therapies and 22.1% had hematological malignancies. Most frequent solid tumors were breast (31.3%), lung (15.9%) and gastro-intestinal (GI) (14.3%). Patients received 45.6% Pfizer/BioNTech, 52.8% Moderna and 1.6% Oxford/AstraZeneca. A combination of 2 different vaccines was administered to 11.9%. Interval between D1 and D2 was ≤30 days in 53.1%, 31-90 days in 42.6%, and 91-180 days in 4.3%. Among all patients, 84.1% developed VRAEs after a median of 2 days post-vaccine for a median of 4 days. 74.5% had local symptoms (Sx) (pain, sensitivity and/or redness at injection site and/or arm) and 65.8% had systemic Sx. Most frequent systemic Sx were fatigue, chills or myalgia (39.4%), GI (6.3%) and fever (2.9%). Most patients (90.7%) described their Sx as having no / minimal impact (Gr 1), 7.8% reported seeking medical consultation (Gr 2), and 1.5% lead to hospitalization (Gr 3) (1 cardiovascular event, 1 infection;causality with concurrent systemic treatment not excluded and 1 due to malignancy). Gr 2, but not Gr 3, VRAEs were more common after D2 (11.4% vs 2.5%, p = 0.03). 41.7% considered their Sx as a new health problem. On multivariate analysis, younger age and female sex were significantly associated with the development of any Sx (OR 1.08, p = 0.01;OR 2.92, p = 0.02, respectively) and local Sx (OR 1.04, p = 0.04;OR 2.19, p = 0.04), but not systemic Sx or new health problem. Conclusions: Patients experienced mostly minor and transient symptoms post-vaccination;few perceived these as a new health problem. COVID-19 vaccination is overall safe and well-tolerated among cancer patients.