December 10, 2023
By Dibash Kumar Das, PhD
In the dynamically evolving landscape of large B-cell lymphomas (LBCLs), the classification and treatment paradigms have undergone significant transformations. Notably, the introduction of CD19-targeted CAR T-cell therapy (CAR-T) has marked a pivotal shift in the treatment approach.
Initially approved as a third-line treatment in 2017, CAR-T is now indicated for second-line therapy (2L) in patients with relapsed or refractory (R/R) LBCL. A new study, presented at the 65th ASH Annual Meeting and Exposition, aimed to provide a comprehensive overview of disease characteristics, treatment patterns, and survival outcomes in patients with R/R LBCL undergoing two or more lines of systemic therapy across different treatment eras (Abstract 307).
A robust database was established, incorporating data from patients with R/R LBCL across eight U.S. academic centers participating in the Lymphoma Epidemiology of Outcomes (LEO) Cohort study (NCT02736357) and the Consortium of Real World Evidence (CReWE). Distinguishing itself from the SCHOLAR-1 dataset, this cohort included all patients receiving 2L, irrespective of the timing of progression/relapse. The analysis focused on eligible patients aged 18 years or older who received 2L between 2002 and 2022, excluding specific subtypes.
Prognostic factors, therapy details, and outcomes, including event-free survival (EFS) and overall survival (OS), were abstracted for all lines of therapy. Treatment eras were categorized as pre-CAR-T (2002-2010), CAR-T available via clinical trial (2011-2017), and post-FDA approval of CAR-T (2018-2022).
Out of 1,760 patients initiating 2L for R/R disease, 1,523 were eligible for analysis. The key findings include the following
• Median age at the start of 2L was 62 with 65 percent male and 11 percent non-White.
• The majority had high-grade subtypes (16%).
• Median time from diagnosis to 2L was 8.7 months, with various relapse scenarios.
• At a median follow-up of 48 months from 2L initiation, 61 percent of patients had died, primarily due to progressive lymphoma.
• Academic medical centers administered 2L in 83 percent of cases with 14 percent of patients enrolled in clinical trials.
• Intent for autologous stem cell transplant (ASCT) and/or CAR-T was planned for 65 percent of patients at 2L.
To learn more about the study, Oncology Times reached out to the study presenter, Jean L. Koff, MD, MSc, Associate Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine. Within the Bone Marrow and Stem Cell Transplant Center, Koff is a clinical investigator specializing in lymphoma.
Oncology Times: How did the availability of CAR-T impact patterns of care and outcomes for patients receiving 2L treatment for relapsed or refractory LBCL? Were there differences observed across distinct treatment eras (e.g., pre-CAR-T, clinical trial availability, and post-FDA approval of CAR-T)?
Koff: “In our dataset, we observed increased use of CAR-T in 2L in the 2018-2022 era (13% of patients receiving 2L for LBCL), as well as a corresponding decrease in the proportion of patients who received autologous stem cell transplant (ASCT) in 2L (from 34-35% in 2002-2017, down to 25% in the post-FDA approval era of 2018-2022). Our data set is unique in that it allowed us to gauge how many patients were intended for CAR-T or ASCT (i.e., intended for therapy with curative intent), regardless of whether they received either therapy. Interestingly, we observed a decrease in the proportion of patients not intended for curative therapy, from 44 percent in the pre-CAR-T era to 27 percent in the 2018-2022 era. This suggests more patients are being considered for curative therapy in the era of CAR-T availability. We observed increased participation in 2L clinical trials in the more recent era (9% in 2002-2017 compared to 17% in 2018-2022), which we suspect is driven by the availability of CAR-T in 2L on trial. However, it is worth noting that many trials using other agents now approved in relapsed/refractory LBCL were ongoing during this period.
“In terms of outcomes, event-free survival (EFS) and overall survival (OS) improved significantly for patients initiating 2L in eras when CAR-T was available, compared to the pre-CAR-T era of 2002-2010. For instance, median OS for the pre-CAR-T era was 1.04 years, compared to 1.72 years in the 2018-2022 era. Moreover, 5-year OS improved from 27.2 percent in the pre-CAR-T era to 38.5 percent in the 2018-2022 era.”
Oncology Times: What are implications of these findings for clinicians and patients dealing with relapsed or refractory LBCL? How might the study influence future treatment approaches and strategies for improving patient survival?
Koff: “Our study is the first-ever large-scale attempt to describe patterns of care and outcomes in LBCL 2L in the modern era, inclusive of all treatment approaches. We observed increased proportions of patients being considered for curative therapy in 2L, increased uptake of CAR-T in 2L, and improved survival outcomes in the period following FDA approval of CAR-T.
“Given that 5-year OS remains less than 40 percent in patients who require 2L treatment for LBCL even in the most recent era, more work is needed to identify treatment approaches that result in long-term survival for more patients with relapsed/refractory LBCL. Our data thus provide a benchmark for future drug development.”
Dibash Kumar Das, PhD, is a contributing writer.