Clinical Summary: 

• Design/Population: This phase 3 trial compared polatuzumab vedotin plus R-ICE vs R-ICE alone in patients with relapsed or refractory large B-cell lymphoma undergoing second-line therapy before autologous stem cell transplant or CAR T-cell therapy.
• Key Outcomes: Polatuzumab-R-ICE did not improve event-free survival, progression-free survival, or overall survival in the overall study population, although exploratory subgroup analyses suggested benefit in select patient populations.
• Clinical Relevance: While the addition of polatuzumab did not improve outcomes overall, certain subgroups may derive benefit and warrant further study.

Results from a phase 3 study demonstrated that the addition of polatuzumab vedotin to rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE) did not improve outcomes among patients with relapsed or refractory large B-cell lymphoma. 

These results were presented by Bertram Glass, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden. 

In this open-label study, 294 patients with first relapse or progression of large B-cell lymphoma were randomized 1:1 to receive either polatuzumab vedotin plus standard R-ICE (n = 147) or standard R-ICE alone (n = 147) followed by consolidation with autologous stem cell transplant (ASCT) or CAR T-cell therapy at the investigator’s discretion. The primary end point was event-free survival (EFS). Key secondary end points included progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 24.6 months, the 2-year EFS rate was 26% with polatuzumab plus R-ICE and 30% with standard R-ICE (P = .901). The corresponding 2-year PFS rates were 47% and 41%, respectively, while the 2-year OS rates were 75% and 64%.

Among patients with diffuse large B-cell lymphoma, polatuzumab plus R-ICE improved the 2-year PFS rate compared with standard R-ICE (52% vs 42%; P = .040) and the 2-year OS rate (77% vs 61%; P = .033). Similar improvements in PFS and OS were observed among patients with relapsed disease (66% vs 46% [P = .004] and 87% vs 71% [P = .015], respectively), bulky disease (45% vs 23% [P = .006] and 76% vs 39% [P = .011]), and elevated lactate dehydrogenase levels (44% vs 31% [P = .034] and 67% vs 49% [P = .036]). Patients with non-germinal center B-cell subtype disease also experienced improved 2-year PFS with polatuzumab plus R-ICE (54% vs 34%; P = .040).

Primary refractory disease was the strongest adverse prognostic factor for EFS, PFS, and OS (P < .0001). Additional adverse prognostic factors for EFS included elevated lactate dehydrogenase (P = .005) and ECOG performance status >1 (P = .032). Age older than 60 years was also associated with worse OS (P = .031).

Grade ≥3 infections were reported in 23 patients in the polatuzumab plus R-ICE arm and 12 patients in the standard R-ICE arm (P = .048). Other toxicities were equally reported between treatment arms. There were 2 treatment-related deaths reported, due to ischemic colitis (polatuzumab plus R-ICE arm) and cardiorespiratory arrest (standard R-ICE arm). 

“This study could not detect a benefit of applying [polatuzumab plus R-ICE] over R-ICE as second line treatment,” concluded Dr Glass. “However, pts with [diffuse large B-cell lymphoma], relapsed disease (in contrast to those with primary refractory disease) and those with high tumour burden (bulky disease, high LDH) may clinically benefit from [polatuzumab plus R-ICE] instead of R-ICE when given prior to consolidative therapy with ASCT or CAR T.” 

Source:

Glass B, Saidy AO, Michael R, et al. Polatuzumaba vedotin plus rituximab, ifosfamide, carboplatin, etoposide (POLA-R-ICE) vs R-ICE as second-line treatment in large B cell lymphoma (LBCL). Final analysis of a randomized phase 3 study. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-3674.