Real-World Study Reveals Key Insights into DLBCL Treatment Patterns, Outcomes

Diffuse large B-cell Lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin lymphoma cases diagnosed each year in the US. Data show that up to 50% of patients will develop refractory or relapsed (R/R) disease, which often has a poor prognosis.¹ With new advances in treatment, a new study has aimed to provide data regarding the current characteristics, treatment patterns, and outcomes of DLBCL and to identify real-world unmet needs in its management. Findings were recently published in Cancer Medicine.²

Patients newly diagnosed with DLBCL between January 2016 and March 2021 who were 18 years or older and had started on first-line (1L) therapy were identified from the COTA real-world database. A total of 1347 patients with DLBCL were identified as eligible. Males comprised 54.9% of patients, and the mean patient age was 67 years at diagnosis. More than 38% of patients had stage IV disease. Patients with primary central nervous system DLBCL were not included in this study due to differences in the treatment paradigms.

Of the 1347 patients who received 1L therapy, 340 (25.2%) progressed to receive second-line (2L) treatment, with 12.8% of patients experiencing refractory disease and 11.7% experiencing disease relapse. Of the 340 patients who received 2L therapy, 141 (41.5%) progressed to receive third-line (3L) treatment, and of this cohort, 41 (36.2%) progressed to fourth-line or greater treatment (4L+). The median follow-up time was 26.7 months from 1L initiation to 2L therapy.

As patients progressed from 1L to later lines of therapy (LOTs), treatment patterns became more individualized. The most common treatments for each LOT were rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone (R-CHOP) (63.6%) in 1L, which is similar to previous studies2; followed by 5.35% receiving dose-adjusted etoposide phosphate, prednisone, Oncovin, cyclophosphamide, doxorubicin hydrochloride, and rituximab (DA-EPOCH-R). Among patients who received 2L therapy, stem cell transplant (SCT), along with various salvage regimens (17.9%); rituximab plus ifosfamide, carboplatin, and etoposide phosphate (13.5%), and bendamustine and rituximab (BR; 10.3%) were most used. In patients who received 3L regimens, the most common treatments were polatuzumab plus BR (9.9%), followed by chimeric antigen receptor T‐cell therapy (CAR T) with or without supplemental regimens (9.9%) and SCT with various salvage regimens (9.9%). CART (11.8%) was the most common therapy in patients who received 4L+ treatment. Premature discontinuation rates were higher in later LOTs, at 16.0%, 41.8%, 39.0%, and 56.9% for 1L, 2L, 3L, and 4L, respectively.

Patients who received a later LOT also had lower real-world OS rates, comparable with those seen in the literature. One-, 3‐, and 5-year real-world OS rates in 1L treatment were 88.5%, 78.4%, and 73.5%, respectively. The 1- and 3-year rates for 2L therapy were 62.4% and 46.4%, respectively. The 1-year real-world OS rates for 3L- and 4L-treated patients were 31.5% and 29.8%, respectively.

The study included a diverse population of patient characteristics across LOTs, with differences in age, disease stage, prior treatments, and comorbidities. Such variations have significant implications for treatment decisions, highlighting the importance of personalized approaches in managing DLBCL.

Since much of the existing literature focuses on patient populations with DLBCL from 2018 and earlier, the utilization and outcomes of newer treatment options for R/R-DLBCL, such as CAR T, targeted agents, and polatuzumab in the real world have not been clearly understood or quantified. This study highlights the emergence of novel therapies and their integration into clinical practice, underscoring the continually evolving nature of DLBCL management.

The authors concluded, “In this real-world analysis, 25.2% of patients experienced R/R-DLBCL after 1L [treatment] with poor outcomes. Given the findings of this study, there is a high unmet need for novel, safe, and effective treatment options for patients with R/R-DLBCL.”

References

1. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study . Blood. 2017;130(16):1800-1808. doi:10.1182/ blood-2017-03-769620
2. Sineshaw HM, Zettler CM, Prescott J, et al. Real-world patient characteristics, treatment patterns, and treatment outcomes of patients with diffuse large B-cell lymphoma by line of therapy. Cancer Med. 2024;13(7):e7173. doi:10.1002/cam4.7173