Genentech's Polivy (polatuzumab vedotin) in combination with Rituxan (rituximab), cyclophosphamide, doxorubicin, and prednisone (R-CHP) continues to demonstrate a positive impact on outcomes for patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to five-year follow-up data from the Phase III POLARIX study. The data, presented at the 66th American Society of Hematology (ASH) Annual Meeting, reinforce the potential of this regimen as a new standard of care.
The POLARIX trial (NCT03274492) is a Phase III, randomized, double-blind, placebo-controlled study that included 879 patients with previously untreated DLBCL. Patients were randomized 1:1 to receive either Polivy plus R-CHP or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The primary outcome measure was progression-free survival (PFS).
Sustained Overall Survival Trend
After a median follow-up of 60.9 months, exploratory analysis indicated a positive trend in overall survival (OS) in the intent-to-treat (ITT) population favoring Polivy in combination with R-CHP compared to R-CHOP. The results showed a trend in reduction in the risk of death (HR 0.85; 95% CI: 0.63–1.15) for patients with previously untreated DLBCL with the Polivy combination, an improvement on the three-year follow-up data (HR 0.94; 95% CI: 0.67–1.33). According to Genentech, the five-year analysis of POLARIX indicates that the full difference in OS between treatment arms has yet to be observed and an additional two years of follow-up will continue.
Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development, stated, “POLARIX was the first trial to elevate treatment standards for frontline diffuse large B-cell lymphoma in 20 years and we are additionally encouraged by the five-year follow-up results. More than 38,000 people worldwide have been treated with Polivy in combination with R-CHP and these data continue to underscore its potential to improve outcomes for people diagnosed with this aggressive lymphoma.”
Reduced Need for Subsequent Treatments
In addition to the positive trend in OS, an observational analysis suggested nearly 25% fewer follow-up treatments such as radiation, systemic chemotherapy and CAR-T cell therapy were needed in patients receiving Polivy in combination with R-CHP compared to those treated with R-CHOP (38.3% versus 61.7%). This reduction in subsequent treatments could potentially alleviate burdens on patients and healthcare systems.
Durable Remissions
At five years of follow-up, benefits in progression-free survival and disease-free survival with Polivy in combination with R-CHP were maintained, consistent with the three-year follow-up data, reinforcing the potential of Polivy in combination with R-CHP to provide durable and lasting remissions. The latest follow-up data also showed a numerical reduction in death related to patients’ lymphoma in those treated with Polivy in combination with R-CHP compared to those treated with R-CHOP (9.0% versus 11.4%).
Safety Profile
The safety profile of Polivy in combination with R-CHP remains consistent with the known profiles of the individual study medicines, with no new safety signals observed. This reinforces the positive benefit-risk profile of this combination.
Gilles Salles, M.D., Ph.D., chief of Lymphoma Service, Division of Hematological Malignancies, Memorial Sloan Kettering Cancer Center, commented, “Diffuse large B-cell lymphoma is a notoriously challenging cancer to treat, however, Polivy in combination with R-CHP has shown to be a critical advance for patients by helping to reduce relapse and disease progression. The survival trend seen in this follow-up analysis reinforces the potential impact of frontline treatment with Polivy in combination with R-CHP and its role as a standard of care therapy.”
Ongoing Research
Genentech is continuing to investigate Polivy in combination with other molecules, including its bispecific antibodies, in an effort to further elevate treatment standards. Studies include the Phase III SUNMO trial evaluating the efficacy and safety of subcutaneously administered Lunsumio (mosunetuzumab-axgb) in combination with intravenous (IV) Polivy versus IV Rituxan plus gemcitabine and oxaliplatin (R-GemOx) in second-line or later DLBCL, and the Phase III SKYGLO trial investigating the efficacy of Polivy in combination with R-CHP and Columvi (glofitamab-gxbm) versus Polivy in combination with R-CHP in 1L DLBCL.
