Diffuse Large B-Cell Lymphoma Treated With R-CHOP in a Resource-Limited Setting in South Africa: A Real-World Study.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma worldwide and particularly in Africa, where the incidence of HIV is the highest in the world. R-CHOP is the standard of care regimen for DLBCL, but access to rituximab is limited in developing countries. METHODS: This is a retrospective cohort study that included all HIV-negative patients with DLBCL who received R-CHOP at a single institution from January 2012 to December 2017. Clinical and demographic data were collected to assess factors that influenced survival. RESULTS: Seventy-three patients were included. Median age was 55 (17-76), 67.1% of patients were younger than 60 years, and 60.3% were female. Most presented with stages III/IV disease (53.5%) but with good performance status (56.% PS 0 and 1). Progression-free survival at 3 and 5 years was 75% and 69%, and overall survival at 3 and 5 years was 77% and 74%, respectively. Median survival had not been reached with a median follow-up of 3.5 years(0.13-7.9). Overall survival was significantly affected by performance status (P = .04), but not by IPI or age. Survival was significantly associated with response to chemotherapy after 4-5 cycles of R-CHOP (P = 0.005). CONCLUSIONS: Treatment of DLBCL with R-CHOP is feasible and can achieve good outcomes in resource-limited settings with rituximab-based chemotherapy. Poor performance status was the most important adverse prognostic factor in this cohort of HIV-negative patients.

Financial Toxicity, Symptom Burden, Illness Perceptions, and Communication Confidence in Cancer Clinical Trial Participants.

PURPOSE: Cancer clinical trial (CCT) participants are at risk for experiencing adverse associations from financial toxicity, but these remain understudied. METHODS: From July 2015 to July 2017, we prospectively enrolled CCT participants referred for financial assistance and a group of patients matched by age, sex, cancer type, trial, and trial phase. We assessed financial burden of cancer care, cost concerns about CCTs, physical (Edmonton Symptom Assessment Scale [ESAS]) and psychologic (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire), and communication confidence (Perceived Efficacy in Patient-Physician Interactions). Adjusting for age, sex, race, performance status, marital status, income, insurance, and disease status, we examined associations of financial burden and cost concerns with patients' symptoms, illness perceptions, and communication confidence. RESULTS: Of 198 patients, 112 (56.6%) reported financial burden and 82 (41.4%) reported cost concerns. Higher ESAS-total (odds ratio [OR] = 1.03; 95% CI, 1.01 to 1.06; P = .001), PHQ-4 depression (OR = 1.58; 95% CI, 1.20 to 2.08; P < .001), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.02 to 1.55; P = .025), and more negative illness perceptions (OR = 1.04; 95% CI, 1.00 to 1.07; P = .029) were associated with financial burden, but not communication confidence (OR = 0.98; 95% CI, 0.02 to 1.05; P = .587). Higher ESAS-total (OR = 1.03; 95% CI, 1.01 to 1.05; P = .004), PHQ-4 depression (OR = 1.36; 95% CI, 1.08 to 1.71; P = .03), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.03 to 1.53; P = .018), more negative illness perceptions (OR = 1.06; 95% CI, 1.02 to 1.10; P = .001), and decreased communication confidence (OR = 0.93; 95% CI, 0.86 to 1.00; P = .029) were associated with cost concerns. CONCLUSION: In this study of CCT participants, greater symptom burden, more negative illness perceptions, and lower communication confidence were associated with financial toxicity, underscoring the importance of addressing these issues when seeking to alleviate adverse associations of financial toxicity.

Accuracy of Pathologic Diagnosis in Patients With Lymphoma and Survival: A Prospective Analysis From Botswana.

PURPOSE: With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival. METHODS: Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard. RESULTS: The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL. CONCLUSION: In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries.

Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations.

PURPOSE: We evaluated the efficacy and safety of poly-(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 inhibitor veliparib and temozolomide in metastatic breast cancer patients with and without germline BRCA1/2 mutations. METHODS: In this single-arm phase II trial, patients with metastatic breast cancer received veliparib 30 to 40 mg twice daily on days 1 to 7 with concurrent temozolomide 150 mg/m2 on days 1 to 5 of a 28-day cycle. The primary cohort was unselected for BRCA mutation status, and an expansion cohort enrolled only BRCA1/2 carriers. The primary endpoint was objective response rate (ORR) in each cohort. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and evaluation of safety and tolerability. RESULTS: In the primary cohort of 41 unselected patients, which included 9 BRCA mutation carriers, the ORR was 10% and clinical benefit rate at 4 months (CBR) was 27%. In the expansion cohort of 21 BRCA1/2 carriers, the ORR was 14% and CBR was 43%. Among all 30 BRCA1/2 carriers, the ORR was 23% versus 0% among non-carriers. In the subset of BRCA1/2 carriers, the ORR was 32% among platinum-naïve patients versus 9% among platinum-exposed patients. The median PFS was 3.3 months among BRCA1/2 carriers compared to 1.8 months among non-carriers (HR: 0.48, p = 0.006). A longer median PFS of 6.2 months was observed among BRCA1/2 carriers who had no prior platinum therapy. The most common grade 3 and 4 toxicities were thrombocytopenia (32%) and neutropenia (21%) that generally improved with dose modifications. CONCLUSION: Veliparib and temozolomide demonstrated clinical activity in platinum-naïve BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single-agent active dose. Although the study did not meet its primary endpoint in unselected nor BRCA-associated breast cancer, this regimen was further evaluated in the BROCADE 2 study. TRIAL REGISTRATION: NCT01009788 (ClinicalTrials.gov), November 9, 2009.