Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score &gt;3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.</p

Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score &gt;3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.</p

Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

<p>We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment.</p

Involved-nodal radiation therapy leads to lower doses to critical organs-at-risk compared to involved-field radiation therapy

©2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology. Background Involved field radiotherapy (IFRT) after cytotoxic chemotherapy has become the standard of care in treating pediatric patients with Hodgkin lymphoma. However, recent interest in shrinking the treatment volume to involved node radiotherapy (INRT) may allow lower doses to critical organ structures. We dosimetrically compared IFRT and INRT treatment approaches.Methods INRT treatment plans were retrospectively constructed from 17 consecutively treated pediatric patients identified with Hodgkin lymphoma who had been previously treated with conventional IFRT. The radiation doses delivered to organs-at-risk (OARs) with virtual INRT treatment plans based on INRT field design were then compared to the original IFRT treatment plans. Metrics for comparison included mean doses to organs and volumes of organ receiving at least 50% of the original prescription dose (V50%). A one-tailed, paired t-test was then performed to verify statistical significance at an alpha level of 0.05.Results All organs at risk compared in this investigation (kidneys, heart, thyroid, parotids, and lungs) had significantly lower doses of radiation with INRT when compared to IFRT (p \u3c 0.05). Furthermore, the volume of the breast receiving at least 50% of the initial prescription dose was statistically lower in the INRT plans.Conclusions Utilizing the concept of INRT results in a reduction of radiation dose to critical organ structures in pediatric patients with Hodgkin lymphoma when compared to the more traditional method of IFRT

Outcomes and patterns of care in a nationwide cohort of pediatric medulloblastoma: Factors affecting proton therapy utilization

Purpose: We examined national outcomes and patterns of care for pediatric patients with medulloblastoma (MB) in a large observational cohort. Methods and materials: Using the National Cancer Database, we evaluated the clinical features and survival outcomes of patients diagnosed with MB. The association between intervention, covariables, and outcome was assessed in a multivariable Cox analysis and through logistic regression analysis. Survival was estimated using the Kaplan-Meier method. Results: Among the 4032 patients in the National Cancer Database with pediatric brain tumors, 1300 patients met the inclusion criteria of histologic diagnosis, receipt of chemotherapy and radiation, and age ≤18 years. The median age and follow-up were 8.4 years and 4.5 years, respectively. Five-year survival was 79.0%. In the univariate analysis, inferior outcome (overall survival) was associated with rural residence (hazard ratio [HR], 2.78; 95% confidence interval [CI],1.47-5.29; P < .01) and histology (large cell; HR, 1.78; 95% CI,1.08-2.94; P < .05). In multivariable analysis, both remained significant predictors of survival (large cell: HR, 1.68; P < .05; rural residence: HR, 2.74; P < .01). In 2013, the utilization rate of proton therapy (23% of patients) in the United States surpassed intensity modulate radiation therapy (16%), more frequently for patients with higher income (P < .05) or more favorable insurance status (P < .05). Conclusions: As one of the largest data sets on pediatric MB, the observed variations in treatment intervention and survival outcomes may represent a target for further research