December 10, 2023
By Dibash Kumar Das, PhD
Patients with relapsed or refractory (R/R) aggressive large B-cell lymphoma (LBCL) who have already undergone first-line treatment often face a challenging prognosis. In recent years, numerous novel therapies have been approved for the treatment of R/R LBCL. However, conventional chemo-immunotherapy (CIT) regimens continue to be commonly used.
A new study, presented at the 65th ASH Annual Meeting and Exposition, sought to investigate the effectiveness of both CIT and novel therapies in the second line or later (2L+) treatment of patients with R/R LBCL (Abstract 309). Additionally, the study aimed to analyze the association between clinical characteristics of patients and real-world treatment outcomes.
This multi-site retrospective observational study involved patients aged 18 years or older with R/R LBCL in the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort. These patients were followed from January 1, 2015, to February 15, 2023, and treated with either CIT or novel therapy in the 2L+ setting. CIT regimens included various combinations of salvage/palliative chemotherapy, lenalidomide, rituximab, or obinutuzumab. Novel therapies encompassed polatuzumab vedotin plus bendamustine and rituximab (or variations thereof), tafasitamab plus lenalidomide (or variations), and loncastuximab tesirine.
The study evaluated patients' demographic and clinical characteristics from their first confirmed R/R disease diagnosis and initiation of 2L+ therapy. Real-world outcomes, such as overall response rate (ORR), complete response (CR) rate, duration of response (DOR), duration of complete response (DOCR), progression-free survival (PFS), and overall survival (OS), were assessed for all patients and a subgroup of patients with prior chimeric antigen receptor (CAR) T-cell therapy. Multivariable Cox proportional hazards models were employed to examine associations between select clinical characteristics and real-world outcomes.
The study population included patients treated with CIT (653 patients), a pola-based regimen (116 patients), a TAFA-based regimen (55 patients), and lonca (42 patients). Researchers observed the following key findings.
• In the CIT group, ORR was 33.8 percent with 15.5 percent achieving CR. The median PFS (mPFS) was 1.9 months and the median OS (mOS) was 9.1 months.
• The pola group showed an ORR of 42.2 percent, with 24.1 percent achieving CR. The mPFS was 2.5 months and the mOS was 7.8 months.
• The tafa group had an ORR of 25.5 percent with 14.5 percent achieving CR. The mPFS was 2.7 months and the mOS was 8 months.
• In the lonca group, the ORR was 40.5 percent with 21.4 percent achieving CR. The mPFS was 3 months and the mOS was 4.7 months.
To gain deeper insights into the study, Oncology Times interviewed the lead study author, Loretta J. Nastoupil, MD, Director of the Lymphoma Outcomes Database and Section Chief of New Drug Development in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer.
Oncology Times: Were there any notable differences in treatment response or survival outcomes between patients who had prior chimeric antigen receptor (CAR) T-cell therapy and those who did not within each treatment group?
Nastoupil: “The subgroup of patients that had prior CAR T-cell therapy was small limiting strong conclusions from being drawn, particularly when comparing treatment outcomes post-CAR. This is an interesting observation in itself, suggesting that CAR-T is underutilized even among U.S. academic centers with access to CAR. In general, the baseline characteristics were different among the treatment groups and outcomes were poor including those that were CAR-T naïve or exposed.”
Oncology Times: Considering the modest overall response rates and poor overall survival observed in this study, what implications do these findings have for the current treatment landscape of relapsed/refractory large B-cell lymphoma? What future directions should be explored for improving patient outcomes?
Nastoupil: “This study highlights the unmet need for novel drug development. There are important limitations to this dataset, specifically, the CD20xCD3 bispecifics were not included and may provide an effective treatment strategy both for those that are CAR-T naïve or exposed. The sample size is small, particularly, when we start to explore the different treatment groups limiting our ability to draw any conclusions about preferred treatment approaches. We also did not explore sequencing of therapy and its impact on outcomes.
“With several CD19 targeted approaches in the treatment landscapes, it would be helpful to explore whether sequencing matters or whether chemotherapy prior to a T-cell engaging therapy matters. The strength of this data set is that we are able to describe changes in the treatment landscape over time and real-world outcomes to identify unmet needs for drug development.”
Dibash Kumar Das is a contributing writer.