Columvi Extends Overall Survival in Relapsed/Refractory DLBCL Patients: Two-Year Follow-up Data

Breakthrough Clinical Results

Roche announced two-year follow-up data from the Phase III STARGLO study, showing a 40% improvement in overall survival (OS) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with Columvi (glofitamab) plus GemOx compared to MabThera/Rituxan plus GemOx. The study demonstrated a statistically significant and clinically meaningful survival benefit, with a 59% reduction in the risk of disease progression or death. The benefit was maintained across key secondary endpoints, including progression-free survival and complete remission. Columvi's combination with GemOx is approved in over 30 countries for R/R DLBCL patients not eligible for autologous stem cell transplant and is an NCCN category 1 preferred recommendation for second-line treatment.

Latest Estimates of Incidence and Prevalence of Diffuse Large B-cell Lymphoma Globally

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma (NHL) worldwide, accounting for 30% of adult non-Hodgkin lymphomas. Non-Hodgkin lymphomas constitute about 90% of an estimated 3%-4% worldwide distribution of malignant lymphomas among various cancers.

The incidence of NHL is variable and affected by age, gender, racial, and geographic factors. Regional prevalence data shows significant variations:

• In Sabah, Malaysia, DLBCL was found to be the most prevalent type, accounting for 65.1% of NHL cases
• In Ghana, DLBCL constitutes the predominant group (40.9%) among NHL subtypes
• In Pakistan, from a study conducted between 2015-2020, only 6.4% of DLBCL cases were recognized as anaplastic variants
• Epstein-Barr virus (EBV)-positive DLBCL of the elderly accounts for 8-10% of DLBCLs in Asian countries, but is less common in Western populations

In the United States, a study estimated DLBCL prevalence ranging from 63,883 to 142,889 depending on cure rate assumptions (52.8% to 68.9%). With an assumption of no cure, estimated prevalence in the US was 179,475.

Multiple studies have demonstrated race-based disparities in survival among patients with DLBCL across all stages of disease. African Americans with DLBCL may have a poorer prognosis than non-African American populations.

Study Design Parameters and Endpoints in Key DLBCL Trials

Study Design Parameters

Key trials in diffuse large B-cell lymphoma (DLBCL) typically include:

• Phase 2, single-arm and multicenter trials evaluating novel therapies for relapsed/refractory DLBCL
• Randomized controlled trials comparing treatments like Pola-BR with other interventions
• Treatment durations consisting of multiple cycles (28-day cycles common)
• Patient recruitment with specific characteristics (e.g., age ≥60 years, relapsed/refractory status)

Common Trial Endpoints

DLBCL trials consistently measure:

• Overall survival (OS)
• Progression-free survival (PFS)
• Overall response rate (ORR)
• Complete response (CR) rate
• Safety and toxicity profiles
• Freedom from progression (FFP)

Key Trials

(90)Y-ibritumomab Tiuxetan Trial

• Enrolled 55 high-risk elderly patients (age >60 years)
• Treatment: 4 cycles of R-CHOP21 followed by (90)Y-ibritumomab tiuxetan
• Primary endpoints: overall response rate (80%), including 73% complete remissions
• Secondary endpoints: 2-year PFS of 85% and 2-year OS of 86%

Enzastaurin Phase 2 Study

• Included 55 patients (median age 68 years) with 1-5 prior therapies
• Primary endpoints: freedom from progression (FFP) and objective response
• Results: 22% of patients achieved FFP for two cycles, 15% for four cycles

Lenalidomide plus Rituximab Trial

• Enrolled 23 heavily pretreated elderly patients (≥65 years)
• Treatment regimen: Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) plus rituximab (375 mg/m²) on days 1 and 21
• Achieved overall response rate of 35% after induction phase

BTKi Combination Study

• Investigated zanubrutinib or orelabrutinib combined with R-CHOP or R² in newly diagnosed MYD88/CD79B DLBCL
• Enrolled 23 newly diagnosed DLBCL patients with MYD88 and/or CD79B mutations

• Results: Improved outcomes with BTKi+R-CHOP compared to R-CHOP alone:

• ORR: 100% vs 70.6%

• CRR: 94.4% vs 52.9%

• 1-year PFS rate: 88.9% vs 41.2%

These trials demonstrate the evolution of DLBCL treatment approaches, with consistent measurement of response rates, survival outcomes, and safety profiles across different patient populations.