Diffuse Large B-Cell Lymphoma (DLBCL): A Structured Literature Review of the Epidemiology, Treatment Guidelines, and Real-World Treatment Patterns

Introduction

The increasing incidence of DLBCL globally and a rapidly evolving treatment landscape with recent approvals of novel therapies for both frontline and relapsed/refractory (R/R) settings, make it imperative to establish up-to-date epidemiological estimates, describe recent treatment practice guidelines, and real-world treatment guidelines.

Objectives

Literature reviews were conducted to evaluate the current evidence relating to the epidemiology, clinical practice guidelines, and treatment patterns to identify evidence gaps and highlight areas of unmet need.

Methods

Medline®, Embase®, Cochrane databases were searched for studies reporting the incidence, prevalence, and mortality rates associated with DLBCL in both frontline and R/R settings, to identify clinical practice guidelines, and describe treatment patterns globally. Search period was from 2012 to 2021 (inclusive). A search of select hematology conferences was also conducted for the last three years.

Results

Of the 8,989 records screened, 43 epidemiology (North America 21, Europe 11, Asia 7, multiple countries 3, Australia 1), 23 treatment guidelines (North America 6, Europe 13, Asia 4,) and 23 treatment pattern studies (North America 13, Europe 5, Asia 5) were included in the review. Included evidence estimated incidence of DLBCL to range from 2.3 to 13.8 cases per 100,000 person-years, with 5-year cumulative incidence rate of R/R DLBCL from 20.0% to 23.1%. Prevalence for DLBCL ranged from 20.0% to 63.9% among NHL, with about 4.2% to 24.8% of DLBCL patients R/R to frontline treatments. The 5-year overall survival (OS) rate for DLBCL patients ranged from 53.1% to 61.6%. Among R/R patients, 2-year OS rates ranged from 13.9% 16.0%. The 23 guidelines recommended R-CHOP ± RT (radiotherapy) in the frontline setting. For R/R patients eligible for transplant, the guidelines recommended salvage therapy with regimens such as GDP, DHAP, ICE, ESHAP, CHOP and MINE ± R followed by high-dose chemotherapy with autologous stem cell transplant (ASCT). For transplant ineligible patients, the guidelines recommend salvage therapy with bendamustine monotherapy, CEPP, CEOP, DA-EPOCH, GDP, GemOx ± R. Use of targeted therapies including polatuzumab vedotin, brentuximab vedotin, and tafasitamab-cxix + lenalidomide was recommended in US and European guidelines. CAR-T therapies (axicabatagene ciloleucel, tisagenlecluecel, lisocabtagene maraleucel) were recommended for primary refractory (US) and secondary relapse patients (UK).

The 23 country-specific real-world treatment pattern studies were largely aligned with the US, European and Asian guideline recommendations, particularly in the 1L setting. In 1L, RCHOP ± RT was most commonly used across all geographies, with chemotherapy combinations also used. For R/R patients, most studies reported salvage chemotherapy (GDP, ICE, ESHAP, and MINE ± R) followed by SCT. Patients progressing after salvage therapy were administered CAR-T cell therapies in USA and Europe. However, no real-world study using CAR-T cell therapy was identified for Asia. Targeted therapies were used in the real-world setting in US, Europe, and Asia.

Conclusion

DLBCL is characterized by high prevalence in NHL patients. Published evidence on the epidemiology of R/R DLBCL is sparse with limited survival data. From the available data, low survival rates reported in R/R DLBCL indicate that improvements in therapeutic outcomes are needed. There was consensus on the use of salvage regimens in R/R DLBCL, the use of targeted agents varied, and CAR-T therapies were limited to the US and Europe. Further prospective and retrospective studies are warranted to assess global alignment regarding real-world treatment patterns and to ascertain current survival outcomes in R/R DLBCL.

Garg:Merck & Co., Inc.: Current Employment. Takyar:Parexel: Current Employment. Dhawan:Parexel: Current Employment. Saggu:Parexel: Current Employment. Agrawal:Parexel: Current Employment. Hall:Parexel: Current Employment. Raut:Merck & Co., Inc.: Current Employment. Ryland:Merck & Co., Inc.: Current Employment.