DLBCL is an aggressive and the most common type of NHL that can arise in lymph nodes or outside of the lymphatic system (such as in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain). Often, the first sign of DLBCL includes painless, rapid swelling in the neck, underarms, or groin that is caused by enlarged lymph nodes. 

For effective treatment, OROCH-E demonstrated promising results with Pola-R-GemOx at EHA 2025. As per the results, the analysis clearly shows that Pola-R-GemOx significantly improved overall survival (OS) compared to R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). With a median follow-up of 24.6 months, the median OS for the Pola-R-GemOx group was 19.5 months, notably longer than the 12.5 months seen in the R-GemOx group. Additionally, the 24-month OS rate was 44.0% for Pola-R-GemOx versus 33.2% for R-GemOx. The stratified hazard ratio (HR) was 0.60 with a p-value of 0.0017, indicating a statistically significant 40% reduction in the risk of death with Pola-R-GemOx. These results highlight the clear survival benefit of adding polatuzumab vedotin to the standard regimen for this high-risk patient population.

The safety profile shows that Pola-R-GemOx was associated with a longer treatment duration (median 4.8 vs. 2.1 months) and more cycles (median 7.5 vs. 4) compared to R-GemOx. Adverse events (AEs) were common in both groups, but serious AEs and Grade 5 AEs (fatal events) were higher with Pola-R-GemOx (38.3% and 11.7%, respectively) than with R-GemOx (31.2% and 4.0%). Additionally, treatment discontinuation and dose reductions due to AEs occurred more frequently in the Pola-R-GemOx group (23.4% and 24.2%) compared to R-GemOx (8.0% and 11.2%). Overall, while Pola-R-GemOx increased treatment intensity and duration, it also led to higher rates of serious and fatal adverse events.

Peripheral neuropathy was more frequent with Pola-R-GemOx (57.0%) vs. R-GemOx (28.8%), and thrombocytopenia occurred in 53.1% vs. 40.8%, respectively. Hepatic toxicity (32.0% vs. 20.0%) and infections (41.4% vs. 31.2%) were also higher in the Pola-R-GemOx group, with Grade ≥3 infections in 21.9% vs. 9.6%. COVID-19-related adverse events were reported in 20.3% vs. 13.6%. Neutropenia rates were similar (41.4% vs. 41.6%), as were Grade ≥3 anemia (13.3% vs. 15.2%) and febrile neutropenia (2.3% vs. 2.4%). Overall, the Pola-R-GemOx regimen showed increased toxicity, particularly in severe events.

KOL insights

“The POLARGO data reinforce the benefit of combining polatuzumab vedotin with chemotherapy in the treatment of DLBCL.” – Expert Opinion

Conclusion

Roche’s dominance in the DLBCL space began with the approval of RITUXAN in 2007, establishing R-CHOP as the gold standard for first-line treatment. Despite numerous efforts to shift the treatment paradigm, RITUXAN-based regimens remained firmly entrenched—until the arrival of POLIVY. Approved in combination with R-CHP for first-line DLBCL, POLIVY marked the first breakthrough in two decades, rapidly gaining market share and redefining the standard of care.  POLIVY + R-CHP is now approved in over 70 countries, establishing a strong global footprint. The NCCN has recognized it as a Category 1, preferred first-line therapy, highlighting its significance in DLBCL treatment. Its uptake surged following first-line approval in the US, driving global sales to approximately USD 1.3 billion in 2024, with USD 645 million from the US alone.

Roche’s POLIVY, combined with R-CHP, gained US approval for first-line DLBCL after two decades, rapidly gaining traction and positioning itself as the new standard of care. Its growing adoption is reinforced by 5-year POLARIX data demonstrating improved overall survival, with the regimen now used in more than 42,000 patients worldwide. Furthermore, recent results from the Phase II trial add to the growing evidence supporting Pola-R-GemOx as a promising treatment for transplant-ineligible R/R DLBCL patients who have not previously received polatuzumab vedotin. The regimen maintains strong efficacy while presenting manageable side effects such as peripheral neuropathy and infection, and its non–T-cell-depleting profile may help preserve future therapeutic options.