Polatuzumab Vedotin/R-CHP Meets Primary End Point of Progression-Free Survival for DLBCL in POLARIX Phase 3 Trial

Polatuzumab vedotin (Polivy) in combination with rituximab (Rituxan)- cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with standard of care rituximab- cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has met the primary end point of investigator-assessed progression-free survival (PFS) for patients with diffuse large B-cell lymphoma (DLBCL), according to a press release on the phase 3 POLARIX trial (NCT03274492).¹ 

The double-blind study randomized 879 patients 1:1 to receive polatuzumab vedotin plus R-CHP plus a vincristine placebo for 6 cycles, followed by rituximab for 2 cycles, or the control regimen of R-CHOP plus a polatuzumab vedotin placebo for 6 cycles, followed by 2 cycles of rituximab. Additional results from the POLARIX trial will be presented at an upcoming meeting, investigators reported.

“Since 40% of people with DLBCL relapse after initial therapy, achieving meaningful treatment effects in the front-line setting has the potential to be transformative,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a press release. “This [polatuzumab vedotin] regimen is the first in 2 decades to improve [PFS] in DLBCL compared [with] the standard of care, and we look forward to sharing these results with health authorities to bring this important potential new treatment option to patients as soon as possible.”

At the 2018 American Society of Clinical Oncology Annual Meeting, investigators presented a trial in progress poster for the POLARIX trial.² The poster detailed that the study’s inclusion criteria included patients between 18 to 80 years old with CD20-positive DLBCL or a high-grade B-cell lymphoma that is either MYC-positive or contains BCL2 and/or BCL6 rearrangements. An ECOG performance status of 0 to 2 was also required, as well as at least one bi-dimensionally measurable lesion of over 1.5 cm. Exclusion criteria included, prior organ donation, current peripheral neuropathy of grade 2 or higher, and history of indolent lymphoma.

Secondary end points of the study included, PET-CT complete response (CR), event-free survival, 2-year PFS, and overall survival.

Patients who received R-CHP will be closely monitored with PET-CT and CT scans after 4 cycles of treatment, as well as 6-8 weeks after study ends. During the follow-up period, patients will receive CT scans every 6 months for the first 2 years, and then every 12 months for the subsequent 3 to 5 years.

In a study that examined the long-term follow-up of elderly patients who were treated with R-CHOP for DLBCL, 75% of patients achieved a complete response (CR) to initial treatment, as well as an undocumented CR of 63%. In total, 24.3% of patients relapsed and more than 80% of relapses occurred within the first 3 years.³ Approximately 20% of patients had primary refractory disease and did not respond to initial treatment with R-CHOP.

In a phase 1/2 study (NCT01992653), polatuzumab vedotin was examined in combination with R-CHP in a population of patients with previously untreated DLBCL.⁴ Findings from the trial indicated that the overall response rate by PET at the end of treatment was 91%, including a CR rate of 78% and a partial response rate of 13%. At the data cut off of November 4, 2016, the median study duration was 9.5 months, with 1 patient experiencing disease progression.

Additionally, the phase 1b/2 GO29365 study (NCT02257567) examined the combination of polatuzumab vedotin and bendamustine/rituximab in patients with relapsed/refractory DLBCL.⁵ Findings from the trial indicated that the combination yielded a CR rate of 42.5% that was maintained in patients compared with bendamustine alone (17.5%). Data from an extended cohort indicated that the experimental regimen yielded a CR rate of 38.7%.

References:

1: Phase III study shows Roche’s Polivy plus R-CHP is the first regimen in 20 years to significantly improve outcomes in previously untreated aggressive form of lymphoma compared to standard of care. News Release. Roche. August 9, 2021. Accessed August 9, 2021. https://bit.ly/3CwmRLe

2. Tilly H, Flowers C, Friedberg J, et al. A phase 3 study comparing polatuzumab vedotin plus R-CHP versus R-CHOP in patients with DLBCL (POLARIX). J Clin Oncol. 2018;36:TPS7589. doi:10.1200/JCO.2018.36.15_suppl.TPS7589

3. Coiffer B, Thieblemont C, Den Neste EV, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. 2010;116(12):2040-2045. doi:10.1182/blood-2010-03-276246

4. Tilly H, Sharman J, Bartlett N, et al. POLA-R-CHP: Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, prednisone for patients with previously untreated diffuse large B-cell lymphoma.Hem Oncol. 2017. doi:10.1002/hon.2437_79

5. New data presented at ASH 2020 reinforces the benefit/risk profile of fixed-duration Polivy plus bendamustine and MabThera/Rituxan in patients with relapsed or refractory diffuse large B-cell lymphoma. News Release. Roche. December 7, 2020. Accessed August 9, 2021. https://bit.ly/3ixFZjR