Safety and efficacy of rituximab in patients with diffuse large B-cell lymphoma in Malawi: a prospective, single-arm, non-randomised phase 1/2 clinical trial

Abstract

Background There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi.Methods This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18-60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0-2, a CD4 count of 100 cells per µL or higher (if HIVpositive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 10⁹ cells per L or higher, a platelet count of 100 × 10⁹ platelets per L or higher, a serum creatinine concentration of 132•60 µmol/L or less, a total bilirubin concentration of 34•21 µmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1•4 mg/m² (maximum 2 mg/m²), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710.

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

“…Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm, has invasive behavior and a complex origin, and is heterogeneous in clinical presentation, immunophenotype, and molecular genetics ( Locke et al, 2017 ; Kimani et al, 2021 ; Jiang et al, 2022 ). Although combination chemotherapy cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) containing rituximab serves as the backbone of treatment, approximately 30%–40% of patients experience treatment failure or an inevitable relapse, and the number of DLBCL-related fatalities continues to increase ( Maurer et al, 2014 ; Miao et al, 2019 ; Matasar et al, 2021 ).…”

Cancer-Related Stigma in Malawi: Narratives of Cancer Survivors

“…Participants were recruited from previously described existing observational cohorts of patients with breast cancer 17 and lymphoma 18 at KCH. Participants had received treatment according to previously described KCH standards of care for breast cancer 19 and lymphoma, 18 , 20 which are modeled after the National Comprehensive Cancer Network Harmonized Guidelines for Sub‐Saharan Africa. 21 Remission was defined as the disappearance of all evident disease assessed by physical examination, chest radiography, abdominal sonography, and rarely CT scan.…”

Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies

“…In combination with conventional chemotherapy, rituximab has improved the 3-yr survival rate from 82% to 94% for children diagnosed with mature B-NHL in the USA ( Minard-Colin et al, 2020 ). In the first rituximab clinical trial of African adults diagnosed with diffuse large B-cell lymphoma (DLBCL), the 2-yr survival rate was 55% when treated with rituximab and chemotherapy ( Kimani et al, 2021 ), in contrast to chemotherapy only showing a 38% overall survival rate ( Painschab et al, 2019 ). Rituximab has a myriad of ways to instigate tumor cell lysis including direct programmed cell death, complement-mediated cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP) ( Maloney et al, 2002 ).…”