Polatuzumab/Rituximab Display Tolerability in Frail/Older DLBCL Groups

Combination regimens containing rituximab (Rituxan) plus dose-reduced cyclophosphamide, vincristine, doxorubicin, and prednisone (R-mini-CHOP) or polatuzumab vedotin-piiq (Polivy) and rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-pola-mini-CHP) displayed tolerability among patients deemed frail or elderly with diffuse large B-cell lymphoma (DLBCL), according to a safety analysis of the phase 3POLAR BEAR trial (NCT04332822) presented at the European Hematology Association (EHA) 2026 Congress.¹

Specifically, among 300 patients 75 years and older in the investigational R-mini-CHOP (n = 150) and R-pola-mini-CHP control arms (n = 150), serious adverse effects (AEs) were reported in 36.0% vs 42.7% of each of the respective arms, of which 2.7% vs 7.3% were fatal. In the R-pola-mini-CHP arm, 22.7% of serious AEs were related to polatuzumab vedotin, leading to treatment discontinuation in 6% of patients.

Moreover, the rate of grade 3 or higher AEs was generally consistent between arms, although a higher proportion of patients treated with polatuzumab vedotin experienced grade 3 or higher infections (16.7% vs 10.7%), gastrointestinal (GI) tract events (8% vs 3.3%), and cardiovascular toxicities (8% vs 3.3%).

Pooled progression-free survival (PFS) data showed that after a median follow-up of 2.54 years (IQR, 1.71-3.91), the 2-year PFS rate was 63% (95% CI, 57%-69%) among all patients treated on the trial. This compared favorably with prior findings from the phase 3 SENIOR trial, which showed a 2-year PFS rate of 56% with R-mini-CHOP in a similar population, which included patients 80 years and older with untreated CD20-positive DLBCL.² The projected date for the final PFS readout will be presented in the third or fourth quarter of 2027.

Additionally, the pooled overall survival (OS) data showed a 2-year rate of 76% (95% CI, 70%-80%). In the PFS analysis, the outcomes between patients younger than 80 years and those 80 years to 89 years were similar.

“We can say that both the [R-mini-CHOP and R-pola-mini-CHP] regimens are tolerable treatments in patients [who are elderly or frail] with DLBCL,” Mats Jerkeman, MD, professor in Clinical Oncology at Lund University and senior consultant at Skane University Hospital, Lund, Sweden, stated in the presentation.¹ “Although R-pola-mini-CHP was associated with more grade 3 or 4 toxicity—especially infections, GI toxicity and cardiovascular toxicity—it’s really encouraging to see the 2-year PFS [rate] of 63% and OS at 2 years of 76%.”

Additionally, patients who scored 10 or higher on the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) displayed comparable PFS outcomes vs those with those who scored up to 9. Similar outcomes were observed among patients regardless of Instrumental Activities of Daily Life (IADL) – Complex independent living skills or Activities of Daily Life (ADL) – Basic self-care tasks scores.

Patients 80 years or older or those 75 to 80 years old who were deemed frail with histologically confirmed aggressive B-cell lymphoma were eligible to enroll on the study. Additionally, inclusion criteria included stage II to IV disease and a WHO performance status of 0 to 3. Patients were deemed frail if they had one or more of the following:

• An ADL score of 5 or less,
• 3 or more grade 3 CIRS-G comorbidities,
• And/or at least 1 grade 4 CIRS-G comorbidity

After a screening period of 4 or fewer weeks, patients were randomly assigned 1:1 to receive the polatuzumab vedotin regimen or R-mini-CHOP. Treatment persisted for 18 weeks, or six 3-week cycles. Polatuzumab vedotin was given at 1.8 mg/kg.

Patients in the R-mini-CHOP and R-pola-mini-CHP arms had a median age of 82 years (IQR, 80-85) and 82 years (IQR, 80-84), respectively. Moreover, 15.3% vs 17.3% were younger than 80, 40.0% vs 43.3% had a WHO performance status of 1, and 87.3% vs 81.3% had DLBCL histology.

Efficacy assessments occurred at 6 weeks, followed by at 3 months, 6 months, 12 months, and 24 months. Follow-up visits were conducted every 3 months after treatment up to 24 months, followed by 30 months and 36 months.

The primary end point of the trial was PFS. The target HR for PFS was 0.63 based on the phase 3 POLARIX trial (NCT03274492), with at least 158 events necessary to achieve at least 80% power with type I error α = 0.05.

References

1. Jerkeman M, Ferreri A, Brown P, et al. Safety data and initial pooled efficacy data from the Nordic Lymphoma Group phase 3 POLAR BEAR trial in elderly or frail patients with diffuse large B-cell lymphoma: R-pola-mini-CHP vs. R-mini-CHOP. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S238.
2. Oberic L, Peyrade F, Puyade M, et al. Subcutaneous rituximab-miniCHOP compared with subcutaneous rituximab-miniCHOP plus lenalidomide in diffuse large B-cell lymphoma for patients age 80 years or older. J Clin Oncol. 2021;39(11):1203-1213. doi:10.1200/JCO.20.02666
3. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304