Anna Magee

BACKGROUND: Phase I and Phase II studies in patients with moderate to severe plaque psoriasis demonstrated that intravenous (IV) efalizumab improved clinical signs and symptoms and was well tolerated. OBJECTIVE: To determine if subcutaneous (SC) delivery of efalizumab improves chronic plaque psoriasis and demonstrates an acceptable safety profile. METHODS: This was a Phase I, open-label, single- and multiple-dose, escalating-dose study. Subjects received a single dose of efalizumab (0.3 mg/kg/wk SC) or escalating multiple doses of efalizumab (0.50-2.0 mg/kg/wk SC). Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI), target lesion assessment, and Physician's Global Assessment (PGA). Safety was assessed by evaluating adverse events, clinical laboratory test results, physical examination results, immunologic responses, and vital signs. RESULTS: PASI score, target lesion assessment, and PGA showed improvement of approximately 40%-60% in signs and symptoms of plaque psoriasis by day 56. Mean PASI scores were still declining at the end of the eight-week dosing period, suggesting that longer duration of treatment would be more effective. By day 91, mean PASI scores were 16.2 vs. 14.6 at day 56 in the 0.5-1.0-mg/kg/wk group and 11.7 vs. 10.1 in the 1.0-2.0-mg/kg/wk group. This demonstrates that, on average, patients maintained their treatment benefit during the 42-day followup period. Overall, there were considerably fewer adverse events than in previous IV studies. These consisted principally of mild to moderate headache, pain, and rhinitis. No allergic reactions were observed. Antibodies to efalizumab were observed in only one subject (2%) and did not have any clinical relevance. CONCLUSION: The SC administration of eight weekly doses of efalizumab improves signs and symptoms of psoriasis. The treatment was safe and very well tolerated. In comparison to previously published results with IV efalizumab, SC administration of efalizumab improves overall safety and tolerability, with the additional advantage of greater convenience.

BACKGROUND: The treatment of nonmelanoma skin cancer (NMSC) in the elderly population is a source of significant debate. Mohs micrographic surgery (MMS) is a highly effective treatment option yet not every patient with a cutaneous malignancy that meets appropriate use criteria (AUC) should be treated with surgery. OBJECTIVE: The purpose of this study was to use the Karnofsky Performance Status (KPS) scale to categorize the functional status of patients aged 75 years and older who required treatment of NMSC. The authors wanted to see whether functionality played a role on the treatment selection. METHODS: Patients aged 75 years and older presenting for biopsy of a suspected NMSC that met AUC for MMS were included in the study. Trained medical assistants used the KPS scale to assess patient functionality. Treatment modality was recorded once the biopsy confirmed the NMSC. RESULTS: A cohort of 203 subjects met inclusion criteria for the study. There was a statistically significant difference in utilization of surgical treatments between high and low functionality patients (p = .03). CONCLUSION: Dermatologists consider patient functionality when selecting a treatment for NMSC and use less invasive modalities for patients with poor functional status, even when the tumor meets AUC.

Background: Phase I and Phase II studies in patients with moderate to severe plaque psoriasis demonstrated that intravenous (TV) efalizumab improved clinical signs and symptoms and was well tolerated. Objective: To determine if subcutaneous (SC) delivery of efalizumab improves chronic plaque psoriasis and demonstrates an acceptable safety profile. Methods: This was a Phase I, open-label, single- and multiple-dose, escalating-dose study. Subjects received a single dose of efalizumab (0.3 mg/kg/wk SC) or escalating multiple doses of efalizumab (0.50–2.0 mg/kg/wk SC). Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI), target lesion assessment, and Physician's Global Assessment (PGA). Safety was assessed by evaluating adverse events, clinical laboratory test results, physical examination results, immunologic responses, and vital signs. Results: PASI score, target lesion assessment, and PGA showed improvement of approximately 40%–60% in signs and symptoms of plaque psoriasis by day 56. Mean PASI scores were still declining at the end of the eight-week dosing period, suggesting that longer duration of treatment would be more effective. By day 91, mean PASI scores were 16.2 vs. 14.6 at day 56 in the 0.5–1.0-mg/kg/wk group and 11.7 vs. 10.1 in the 1.0–2.0-mg/kg/wk group. This demonstrates that, on average, patients maintained their treatment benefit during the 42-day followup period. Overall, there were considerably fewer adverse events than in previous IV studies. These consisted principally of mild to moderate headache, pain, and rhinitis. No allergic reactions were observed. Antibodies to efalizumab were observed in only one subject (2%) and did not have any clinical relevance. Conclusion: The SC administration of eight weekly doses of efalizumab improves signs and symptoms of psoriasis. The treatment was safe and very well tolerated. In comparison to previously published results with IV efalizumab, SC administration of efalizumab improves overall safety and tolerability, with the additional advantage of greater convenience.

Abstract Background The Eastern Cooperative Oncology Group performance status (ECOG PS) represents the standard for assessing health status prior to CAR-T cell treatment, but is limited by interobserver variability and low granularity. To address this limitation, we implemented a standardized and objective assessment based on two bedside physical fitness tests that evaluate functional capacity in patients with hematologic malignancies undergoing CAR T-cell therapy. This pilot study aims to improve patient stratification by analyzing associations of physical performance with CAR-T-related toxicities and clinical outcomes. Methods We prospectively evaluated 50 patients undergoing standard-of-care CD19 and BCMA CAR-T treatment for hematologic malignancies (including LBCL, MCL, B-ALL, and MM). In addition to ECOG PS, Barthel Index, and HCT-CI scoring, all patients underwent two bedside physical performance tests: i) 10-meter walking test (gait speed), and ii) 30-second sit-to-stand test. Patients completing both tests within reference values were classified as fit; those failing at least one were classified as unfit. Frailty was assessed using a modified Short Physical Performance Battery (SPPB). Clinical endpoints included nutritional indices (mGPS, PNI), treatment-related toxicities (CRS, ICANS, ICAHT), hospitalization duration, as well as progression-free survival (PFS) and overall survival (OS).Body composition analysis (BCA) was performed on pre-therapeutic PET/CT images using the Body-and-Organ-Analysis segmentation tool by the Ship-AI group, calculating sarcopenia index (muscle volume/bone volume) and fat index (total adipose tissue volume/bone volume). Kaplan-Meier estimates were used to examine survival outcomes. Results Of the 50 prospectively evaluated patients, 23 (46%) were classified as unfit and 27 (54%) as fit. The relative ECOG PS distribution showed no statistically significant difference between groups (p=0.27), but a trend toward higher ECOG PS in unfit: among unfit patients, 21.7% had ECOG 0, 60.9% ECOG 1, and 17.4% ECOG ≥2; in fit patients, the distribution was 22.2%, 74.1%, and 3.7%. This underscores the limited discriminatory power of ECOG PS alone in capturing the full spectrum of functional status. Fitness correlated significantly with the validated 5-item FRAIL scale (score 0-5; ρ = –0.46, p=0.0009), supporting its role in capturing functional vulnerability. SPPB (ρ = 0.36, p = 0.01) and Barthel Index (ρ = 0.37, p = 0.009) also correlated moderately with fitness, while HCT-CI showed no relevant association with functional metrics (p=0.48). Of interest, unfit patients were more likely to have lost weight (at least 5% reduction in BMI) in the 3 months prior to treatment. Unfit patients had higher pre-lymphodepletion Ferritin levels (605 vs. 383 ng/ml, p=0.03), and a trend toward elevated NT-proBNP (783 vs. 350 pg/mL, p=0.13), reflecting subclinical systemic inflammation and potential cardiac stress. They more frequently had longer hospital stays (median 18 vs. 11 days) and a trend toward increased grade ≥2 CRS (39.1% vs. 25.9%, p=0.5) and high-risk CAR-HEMATOTOX scores (26.1% vs 11.1%, p=0.06). On the other hand, the distribution of ICAHT and ICANS grades was comparable between both groups. Notably, fit patients achieved significantly higher CR rates (52% vs. 21.7%, p=0.04). BCA revealed a higher sarcopenia index in fit (mean ± SD: 4.03 ± 0.86) compared to unfit individuals (3.63 ± 0.56), reflecting greater muscle mass. On the other hand, fat index was comparable between groups (9.87 ± 7.27 vs. 9.87 ± 4.44). Univariable Cox models did not reveal statistically significant association between BCA and OS. Unfit patients trended toward lower PNI and higher mGPS, indicating poorer nutritional and inflammatory profiles. Conclusions In this prospective single-center pilot study, we established an objective physical performance testing and delineate its association with radiomic BCA and frailty assessment in CAR-T recipients. While ECOG PS remains a widely established clinical tool, the objective assessment provided additional granularity in capturing patient's functional capacity and demonstrated an improved identification of patients at risk for inferior outcomes with CAR-T therapy. These findings highlight the prognostic value of standardized functional metrics and support their integration into clinical trials and routine care to potentially enable more personalized treatment and rehabilitation measures.