Source: European Hematology Association (EHA) 2025 Congress
Polatuzumab vedotin added to rituximab-gemcitabine-oxaliplatin (Pola-R-GemOx) significantly extends overall survival compared to R-GemOx alone in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with a 40% reduction in death risk (HR 0.60, P=.0017). This provides clinicians with a new chemotherapy backbone option that avoids bendamustine and its negative impact on subsequent T-cell-engaging therapies. The survival benefit comes with increased toxicity, particularly infections and peripheral neuropathy.
Study Design & Population
- Phase 3 randomized controlled trial (POLARGO)
- 255 patients with relapsed or refractory DLBCL
- Randomized to Pola-R-GemOx vs R-GemOx for up to 8 cycles
- Key enrollment criterion: no prior polatuzumab exposure
- Equal efficacy across cell of origin subtypes (activated B-cell vs germinal center)
Key Findings
- Overall survival: 19.5 months (Pola-R-GemOx) vs 12.5 months (R-GemOx); HR 0.60 (95% CI, 0.43–0.83; P=.0017)
- Progression-free survival: 7.4 months vs 2.7 months; HR 0.37 (95% CI, 0.27–0.51; P<.0001)
- Treatment exposure: median 7.5 cycles (Pola-R-GemOx) vs 4.0 cycles (R-GemOx)
- No differential benefit by cell of origin subtype (ABC vs GCB)
Clinical Implications
- Provides alternative to bendamustine-based regimens for relapsed/refractory DLBCL
- Preserves future T-cell-engaging therapy options by avoiding bendamustine
- Standard treatment option for appropriate patients with relapsed/refractory disease
- Results comparable to recent STARGLO trial with similar R-GemOx control arm performance
Limitations
- Increased toxicity burden: infections (41.4% vs 31.2%), peripheral neuropathy (57.0% vs 28.8%)
- Higher grade 5 adverse events: 11.7% vs 4.0% (two-thirds were infections)
- Study conducted during “peak COVID” period, potentially inflating infection rates
- Only applicable to polatuzumab-naive patients (prior exposure was exclusion criterion)
- Cross-trial comparison limitations with competing regimens