Glofitamab Plus Polatuzumab Shows Strong Responses in R/R LBCL
Key Clinical Summary
- Glofitamab plus polatuzumab vedotin (Glofit-Pola) achieved a 78.3% overall response rate and 59.7% complete response (CR) rate in relapsed or refractory large B-cell lymphoma (R/R LBCL).
- Median progression-free survival (PFS) was 12.3 months, with overall survival reaching 33.8 months at 32.7 months follow-up.
- Cytokine release syndrome (CRS) was the most common adverse event (43.4%), with most cases low grade and manageable.
R/R LBCL, particularly high-grade B-cell lymphoma (HGBCL), continues to represent a major unmet clinical need. A phase 1b/2 multicenter study (NCT03533283) evaluated the efficacy and safety of Glofit-Pola, including in patients previously treated with chimeric antigen receptor (CAR) T-cell therapy.
Study Findings
In this open-label trial, 129 patients with R/R LBCL received at least 1 dose of Glofit-Pola. The median age was 67 years, and patients had received a median of 2 prior lines of therapy; 21.7% had prior CAR T-cell treatment.
The combination demonstrated robust efficacy. The overall response rate was 78.3%, with a CR rate of 59.7%. Median PFS reached 12.3 months, while median overall survival was 33.8 months after a median follow-up of 32.7 months.
Notably, high-risk subgroups showed meaningful benefit. Patients with HGBCL achieved a CR rate of 65.9%, while those with prior CAR T-cell therapy had a CR rate of 50.0%. Patients with primary refractory disease also demonstrated strong responses (CR rate 52.5%).
Safety findings were consistent with known profiles of the individual agents. CRS occurred in 43.4% of patients, primarily grade 1-2, with a median resolution of 2 days. Grade 3-4 adverse events occurred in 58.9% of patients, and 9.3% experienced grade 5 events. Treatment discontinuation due to adverse events occurred in 14.7% of patients.
Pharmacodynamic analyses showed sustained T-cell activation and expansion without the lymphodepletion typically seen with CAR T-cell therapy. B-cell recovery was observed 18-24 months after treatment completion.
Clinical Implications
For payers and managed care stakeholders, Glofit-Pola represents a potentially important addition to the treatment landscape for R/R LBCL. The regimen offers high response rates and durability comparable to CAR T-cell therapies but with key logistical advantages.
Unlike CAR T-cell therapy, Glofit-Pola is an off-the-shelf, fixed-duration regimen that avoids manufacturing delays and complex administration. This may improve access and reduce system-level costs associated with hospitalization and specialized care.
The combination also demonstrated consistent efficacy across high-risk populations, including HGBCL and patients with prior CAR T-cell exposure—groups that historically have poor outcomes and limited options. Compared with other regimens such as polatuzumab plus bendamustine and rituximab or tafasitamab plus lenalidomide, Glofit-Pola showed higher response rates and comparable or improved PFS.
The manageable safety profile, particularly the predominance of low-grade CRS, further supports its feasibility in broader clinical settings. However, the single-arm design and heterogeneous population underscore the need for confirmatory randomized data.
Study investigators noted that “high and durable responses” were observed across subgroups, including patients with historically poor prognoses such as HGBCL and those previously treated with CAR T-cell therapy. They emphasized that the safety profile was manageable, with CRS events “well-managed and resolved within a median of 2 days.”
Conclusion
Glofit-Pola demonstrated strong efficacy and manageable safety in heavily pretreated R/R LBCL. Ongoing phase 3 evaluation will further define its role, particularly as a scalable alternative to CAR T-cell therapy in high-risk populations.
Reference
Hutchings M, Sureda A, Bosch F, et al. Efficacy and safety of glofitamab plus polatuzumab vedotin in relapsed/refractory large b-cell lymphoma including high-grade b-cell lymphoma: results from a phase Ib/II trial. J Clin Oncol. 2025;43(36):3788-3798. doi: 10.1200/JCO-25-00992
