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Summary: The treatment pattern and outcomes in patients with indolent B‐cell lymphoma treated during the coronavirus disease 2019 (COVID‐19) pandemic period compared to the prepandemic period are unclear. This was a retrospective population‐based study using administrative databases in Ontario, Canada (follow‐up to 31 March 2022). The primary outcome was treatment pattern; secondary outcomes were death, toxicities, healthcare utilization (emergency department [ED] visit, hospitalization) and SARS‐CoV‐2 outcomes. Adjusted hazard ratios (aHR) from Cox proportional hazards models were used to estimate associations. We identified 4143 patients (1079 pandemic, 3064 prepandemic), with a median age of 69 years. In both time periods, bendamustine (B) + rituximab (BR) was the most frequently prescribed regimen. During the pandemic, fewer patients received R maintenance or completed the full 2‐year course (aHR 0.81, 95% CI 0.71–0.92, p = 0.001). Patients treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p < 0.0001; hospitalization aHR 0.81, 95% CI 0.70–0.94, p = 0.0067) and complications (infection aHR 0.69, 95% CI 0.57–0.82, p < 0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47–0.94, p = 0.020), with no difference in death. Independent of vaccination, active rituximab use was associated with a higher risk of COVID‐19 complications. Despite similar front‐line regimen use, healthcare utilization and admissions for infection were less in the pandemic cohort. [ABSTRACT FROM AUTHOR]

Summary: Bendamustine (B) with rituximab (R) has become the preferred regimen for patients with indolent lymphoma in Ontario, Canada, compared to R with cyclophosphamide, vincristine, prednisone (CVP) or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). We conducted a propensity‐matched retrospective cohort population‐based study of patients treated with R‐CVP/CHOP from 2005 to 2012 and patients treated with BR from 2013 to 2018. The primary outcome was 5‐year overall survival (OS), and secondary outcomes included toxicities and healthcare utilization. The 5‐year OS for patients treated with BR (n = 2023) and R‐CVP/CHOP (n = 2023) was 80% and 75% respectively. Treatment with BR was associated with improved OS (HR 0.79, 95% CI 0.69–0.91). During the first 9 months, patients treated with BR versus R‐CVP/CHOP had a higher number of admissions for infection (22% compared to 17%, p < 0.01) and a higher number of mean ED visits (mean 1.01 ± 1.68 visits vs. 0.85 ± 1.51 visits, p < 0.01). This trend persisted for 3 years. The adjusted 5‐year OS for patients 75 years and older did not differ based on treatment regimen (55.5% for BR vs. 55.4% for R‐CVP/CHOP). Our study supports the use of BR for patients with indolent lymphoma requiring treatment but suggests increased risk of certain toxicities warranting careful patient selection. [ABSTRACT FROM AUTHOR]

We conducted an analysis of indirect costs alongside the LY.12 randomized trial in patients with relapsed or refractory (R/R) aggressive non-Hodgkin lymphoma (NHL). Lost productivity data for Canadian patients and caregivers in the trial were collected at baseline and with each chemotherapy cycle pre-transplant, using an adapted Lost Productivity questionnaire. Mean per patient indirect costs were CAD 2999 for patients in the GDP arm and CAD 3400 in the DHAP arm. A substantial majority was not working or had to reduce their workload during this treatment time. Salvage chemotherapy for R/R aggressive NHL is associated with significant indirect costs to patients and their caregivers. [ABSTRACT FROM AUTHOR]

Summary: Post‐transplant lymphoproliferative disorder (PTLD) may arise after solid organ transplantation, and the most common subtype resembles diffuse large B cell lymphoma (DLBCL). In DLBCL‐type PTLD, the anti‐CD20 antibody rituximab (R) may be combined with chemotherapy (R‐CHOP) or use a strategy (R‐primary; similar to the PTLD‐1 clinical trial) consisting of induction with four weekly doses of R‐alone, without any chemotherapy or sequential R‐CHOP follow‐up. Here we report on a multicentre retrospective cohort of solid organ transplant patients with DLBCL‐type PTLD that were treated with R. In 168 adults, two‐year overall survival (OS) was 63·7% [95% CI (confidence interval) 56·6–71·7%]. No difference in OS was observed, whether patients were treated with R‐CHOP versus the R‐primary strategy. In the 109 patients treated with R‐primary, multivariate analysis found that baseline IPI score and the response to R‐induction predicted OS. Patients who responded to R‐induction had durable remissions without the addition of chemotherapy. Conversely, of the 46 patients who had stable or progressive disease after R‐induction (R‐failure), those who received R‐CHOP had an only marginally improved outcome, with a two‐year OS of 45% (23·1–65·3%) vs. no R‐CHOP at 32% (14·7–49·8%). In real‐world patients, R‐failure and high IPI scores predict a poor outcome in DLBCL‐type PTLD. [ABSTRACT FROM AUTHOR]

Outcomes of patients with relapsed low-grade lymphoma retreated with rituximab are similar to rituximab naïve patients Rituximab combined with chemotherapy has been shown to be superior to chemotherapy alone in patients with relapsed/refractory indolent lymphomas [[1]]. As per the regional funding guidelines, patients had to have at least a one-year treatment-free period between their first- and second-line therapies; this therefore excluded any patients who were refractory to rituximab per this definition. Maintenance rituximab use after second-line chemoimmunotherapy was associated with superior PFS (HR: 0.39 (95%CI: 0.2, 0.77), I p i =.0069), with most patients (19/26 patients, 73%) who received it being in Group 1 (NoR-R). [Extracted from the article]

Background: Brentuximab vedotin is currently approved for patients with relapsed or refractory Hodgkin's lymphoma who previously received an autologous stem cell transplant or two previous multiagent chemotherapy regimens, and for patients with relapsed or refractory systemic anaplastic large-T-cell lymphoma who previously received at least one chemotherapy regimen. A high proportion of patients with CD30-expressing relapsed or refractory lymphomas have durable responses to single-agent brentuximab vedotin and show longer progression-free survival than do patients treated with chemotherapy. In patients with Hodgkin's lymphoma and peripheral T-cell lymphoma, treatment with bendamustine alone only achieves modest improvements in progression-free survival compared with that for chemotherapy. The objective of this study was to explore the safety and clinical activity of the combination of brentuximab vedotin plus bendamustine in heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma and anaplastic large-T-cell lymphoma.Methods: In this international, multicentre, single-arm, phase 1-2 trial, eligible patients were aged 18 years or older, had histologically confirmed relapsed or refractory Hodgkin's lymphoma or anaplastic large-T-cell lymphoma, had biopsy-proven CD30-positive tumours, had an Eastern Cooperative Oncology Group performance status of 2 or less, and received at least one previous multiagent chemotherapy regimen. In phase 1, patients were assigned following a 3+3 dose-escalation design to one of four cohorts to receive one dose of either 1·2 mg/kg or 1·8 mg/kg of brentuximab vedotin intravenously on day 1 of a 21 day cycle, plus one dose of bendamustine (70 mg/m2, 80 mg/m2, or 90 mg/m2) on days 1 and 2 of the treatment cycle. In phase 2, all patients were assigned to receive brentuximab vedotin plus bendamustine at the recommended phase 2 dose from phase 1. The primary endpoints were maximum tolerated dose and dose-limiting toxicity for phase 1, and the proportion of patients achieving an overall response in phase 2. For both phases 1 and 2, all patients receiving at least one dose of study drug were evaluable for toxicity and all patients completing at least one cycle of therapy were evaluable for response. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01657331.Findings: Between July 26, 2012, and May 31, 2017, we enrolled and assigned 65 patients to treatment (64 [98%] with Hodgkin's lymphoma and one [2%] with anaplastic large-T-cell lymphoma; 28 [43%] during phase 1 and 37 [57%] during phase 2). In the phase 1 part, the maximum tolerated dose of the combination was not reached. Dose-limiting toxicities were observed in three (11%) of 28 patients, including grade 4 neutropenia at 1·8 mg/kg brentuximab vedotin plus 80 mg/m2 of bendamustine in two (7%) patients and diffuse rash at 1·2 mg/kg brentuximab vedotin plus 70 mg/m2 of bendamustine in one (4%) patient. The recommended phase 2 dose was deemed to be 1·8 mg/kg of brentuximab vedotin and 90 mg/m2 of bendamustine, which are the standard doses of the drugs when given as single agents. In the phase 2 part, an overall response was achieved in 29 (78% [95% CI 62-91]) of 37 patients. Serious adverse events included grade 3 lung infection in five (14%) of 37 patients in the phase 2, and grade 3-4 neutropenia in 16 (25%) of 65 patients across phases 1 and 2. There were no treatment-related deaths.Interpretation: This study shows that brentuximab vedotin plus bendamustine, with a favourable safety profile, is an active salvage regimen for heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma. This salvage regimen can potentially serve as an efficacious and safe alternative to platinum-based chemotherapy before autologous stem cell transplant.Funding: Seattle Genetics, Lymphoma Research Fund of Columbia University and National Center for Advancing Translational Sciences, and National Institutes of Health. [ABSTRACT FROM AUTHOR]