Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: A prespecified subgroup analysis of high-risk patients from the ECHELON-1 study.

Approximately one-third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD-treated versus ABVD-treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high-risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON-1 shows a favorable benefit-risk balance in high-risk patients.

Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapy.

BACKGROUND: While much cancer research focuses on tumours and their microenvironment, malignancies cause widespread physiologic changes. Cancer and treatment-related sarcopenia, measured with quantitative imaging or as a decrease in overall body mass, are indicative of poor prognosis in elderly diffuse large B-cell lymphoma (DLBCL) patients, skeletal muscle radiodensity (SMD) may be a better prognostic marker. SMD, a measure of muscle radiation attenuation on CT imaging, is more prognostic than sarcopenia or International Prognostic Index (IPI) scores in follicular lymphoma and multiple solid organ malignancies. Low SMD appears to correlate with fat accumulation in muscle and is associated with inflammation. This study set out to examine SMD's prognostic ability in DLBCL. METHODS: All DLBCL patients treated with rituximab-containing therapy between 2004 and 2009 were compared to determine SMD's prognostic ability in this single centre, retrospective study. Pre-treatment CT scans were used to measure SMD and muscle cross-sectional area. Primary endpoints included progression free (PFS) and overall survival (OS) while objective response rates (ORR) were secondary. RESULTS: Of 224 evaluable patients, 116 were identified as having low SMD. Low SMD predicted poorer 5 year PFS, 60 vs. 81% (p = 0.001) and OS, 58 vs. 86% (p < 0.0001). SMD's prognostic ability retained significance in multivariate analysis taking into consideration the Revised International Prognostic Index (R-IPI) and sex. Although high SMD was not predictive of ORR (95.4 vs. 91.4%, p = 0.17), it was strongly associated with radiographic complete response (85 vs. 66%, p = 0.0007). Contrary to previous findings, sarcopenia did not predict for poorer OS but suggested improved OS in elderly DLBCL patients (HR 0.38, p = 0.01). CONCLUSIONS: SMD is a novel prognostic (and potentially treatment predictive) marker independent of R-IPI in DLBCL. It presents an inexpensive yet complementary assessment to R-IPI for prognosticating DLBCL outcomes.

Effects of a Structured Exercise Program on Physical Activity and Fitness in Colon Cancer Survivors: One Year Feasibility Results from the CHALLENGE Trial.

BACKGROUND: There is strong interest in testing lifestyle interventions to improve cancer outcomes; however, the optimal methods for achieving behavior change in large-scale pragmatic trials are unknown. Here, we report the 1-year feasibility results for exercise behavior change in the Canadian Cancer Trials Group CO.21 (CHALLENGE) Trial. METHODS: Between 2009 and 2014, 273 high-risk stage II and III colon cancer survivors from 42 centers in Canada and Australia were randomized to a structured exercise program (SEP; n = 136) or health education materials (HEM; n = 137). The primary feasibility outcome in a prespecified interim analysis was a difference between randomized groups of ≥5 metabolic equivalent task (MET)-hours/week in self-reported recreational physical activity (PA) after at least 250 participants reached the 1-year follow-up. Secondary outcomes included health-related fitness. RESULTS: The SEP group reported an increase in recreational PA of 15.6 MET-hours/week compared with 5.1 MET-hours/week in the HEM group [mean difference = +10.5; 95% confidence interval (CI) = +3.1-+17.9; P = 0.002]. The SEP group also improved relative to the HEM group in predicted VO2max (P = 0.068), 6-minute walk (P < 0.001), 30-second chair stand (P < 0.001), 8-foot up-and-go (P = 0.004), and sit-and-reach (P = 0.08). CONCLUSIONS: The behavior change intervention in the CHALLENGE Trial produced a substantial increase in self-reported recreational PA that met the feasibility criterion for trial continuation, resulted in objective fitness improvements, and is consistent with the amount of PA associated with improved colon cancer outcomes in observational studies. IMPACT: The CHALLENGE Trial is poised to determine the causal effects of PA on colon cancer outcomes. Cancer Epidemiol Biomarkers Prev; 25(6); 969-77. ©2016 AACR.

Skeletal muscle radio-density is an independent predictor of response and outcomes in follicular lymphoma treated with chemoimmunotherapy.

Skeletal muscle radio-density (SMD) measures muscle radiation attenuation (in Hounsfield Units, HU) on computed tomography (CT) scans. Low SMD is prognostic of poor survival in melanoma, however its significance is unknown for hematologic malignancies. We performed a single institution, retrospective review of all follicular lymphoma (FL) patients who received chemoimmunotherapy from 2004-2009. Patient demographics, FL International Prognostic Index 1 (FLIPI-1), progression free (PFS) and overall survival (OS) were collected as primary endpoints. Objective response rates (ORR) were secondary. SMD was calculated using pre-treatment CT scans. In 145 patients reviewed, median values were age 59, FLIPI-1 of 2, stage III, and 8 chemoimmunotherapy cycles received. Median PFS for those with low SMD (<36.6 and <33.1 HU for patients with BMI ≤ 25 and > 25 kg/m2, respectively) compared to those with high SMD was profoundly worse, 69.6 vs. 106.7 months (hazard ratio [HR] 1.85; p = 0.01), respectively. Median OS was not reached in patients with high SMD vs. 92.7 months in low SMD patients (HR 4.02; p = 0.0002). Multivariate analysis supported lower SMD's OS detriment (HR = 3.40; p = 0.002) independent of FLIPI-1 (HR 1.46-2.76, p = 0.05) or gender. Low SMD predicted lower ORR, 83 vs. 96% (p = 0.01). SMD predicts survival independent of FLIPI-1 and potentially chemoimmunotherapy response. SMD is an inexpensive and powerful tool that can complement FLIPI-1.