Response-adapted anti-PD-1-based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE.

This phase 2 trial evaluated PET-adapted nivolumab alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240 mg nivolumab every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, whereas patients with progressive disease at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. Forty-three patients were evaluable for toxicity; 42 were evaluable for response. Thirty-four patients received nivolumab alone, and 9 patients received nivolumab+NICE. No unexpected toxicities were observed after nivolumab or NICE. After nivolumab, the overall response rate (ORR) was 81%, and the CR rate was 71%. Among 9 patients who received NICE, all responded, with 8 (89%) achieving CR. At the end of protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n = 43) were 72% and 95%, respectively. Among 33 patients who bridged directly to AHCT, the 2-year PFS was 94% (95% CI: 78-98). PET-adapted sequential salvage therapy with nivolumab/nivolumab+NICE was well tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This trial was registered at www.clinicaltrials.gov #NCT03016871.

Energy expenditure and heart rate responses to increased loading in individuals with motor complete spinal cord injury performing body weight-supported exercises.

OBJECTIVE: To examine acute metabolic and heart rate responses in individuals with motor complete spinal cord injury (SCI) during stepping and standing with body weight support (BWS). DESIGN: Cohort study. SETTING: Therapeutic exercise research laboratory. PARTICIPANTS: Nonambulatory individuals with chronic, motor complete SCI between T5 and T12 (n=8) and healthy, able-bodied controls (n=8). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Oxygen consumption (V˙o2) and heart rate. RESULTS: Individuals with motor complete SCI performed standing and stepping exercises in a BWS system with manual assistance of lower body kinematics. V˙o2 and heart rate responses were assessed in relation to level of BWS. Weight support was provided by an overhead lift at high (≥50% BWS) or low (20%-35% BWS) levels during stepping and standing. Although participants with motor complete SCI were unable to stand or step without assistance, levels of V˙o2 and heart rate were elevated by 38% and 37%, respectively, when load was maximized during stepping (ie, low BWS). Participants without an SCI (able-bodied group) had a similar acute response to exercise. None of the participants met the target range for V˙o2 response in any of the tasks. However, stepping was sufficient to enable half of the participants in the SCI group to attain the target range for heart rate response to exercise. CONCLUSIONS: Individuals with motor complete SCI exhibit cardiovascular responses during body weight-supported exercise. Findings indicate that body weight-supported stepping provides a minimal cardiovascular challenge for individuals with paraplegia. Emphasis on low weight support during locomotor training can trigger additional heart rate adaptations.