The U.S. Food and Drug Administration (FDA) has approved polatuzumab vedotin-piiq Polivy®; Genentech/Roche)* in combination with rituximab (Rituxan®; Genetech/Biogen), cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index (IPI) score of two or greater.
This FDA decision converts the accelerated approval of polatuzumab vedotin, a first-in-class anti-CD79b antibody-drug conjugate (ADC), in combination with bendamustine and rituximab for relapsed or refractory (R/R) DLBCL after at least two prior therapies to regular approval.
An aggressive disease
CD79b is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polatuzumab vedotin binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin’s lymphoma (NHL) in the United States, accounting for one in thee cases of NHL.
Approximately 31,000 people in the U.S. are projected to be diagnosed with DLBCL in 2023. Globally, approximately 160,000 people are estimated to be diagnosed with DLBCL each year. Limited progress has been made in improving patient outcomes in previously untreated DLBCL over the last two decades.
While many patients are responsive to initial treatment, as many as four in 10 people (approximately 40%) with DLBCL do not respond or relapse. For patients who undergo initial treatment with the standard of care, rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), most relapses occur within two years of starting treatment, and the majority of those who require subsequent lines of therapy have poor outcomes. For these patients salvage therapy options are limited and survival is short.
“It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development.
“Today’s decision from the FDA to approve polatuzumab vedotin in combination with R-CHP in this setting brings a much-needed new treatment option which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.”
The FDA approval of polatuzumab vedotin plus R-CHP for the first-line treatment of DLBCL is based on pivotal data from POLARIX [NCT03274492], an international Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of polatuzumab vedotin + rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL).
The study enrolled 879 patients with previously untreated DLBCL were randomized 1:1 to receive either polatuzumab vedotin plus R-CHP plus a vincristine placebo for six cycles, followed by rituximab for two cycles; or R-CHOP plus a polatuzumab vedotin placebo for six cycles, followed by two cycles of rituximab.
In the study, the risk of disease progression, relapse or death was reduced by 27% with polatuzumab vedotin plus R-CHP (n=440) compared with R-CHOP (n=439; hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). The safety profile was comparable for polatuzumab vedotin plus R-CHP versus R-CHOP, including rates of Grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), Grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%).
The most common AEs were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The most common Grade 3-4 AEs were lymphopenia and neutropenia.
The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma demonstrated a statistically significant and clinically meaningful improvement in PFS compared to R-CHOP.
This approval follows the FDA Oncologic Drugs Advisory Committee (ODAC) vote of 11 to 2 in favor of polatuzumab vedotin in combination with R-CHP for previously untreated DLBCL. More than 70 countries have approved this polatuzumab vedotin combination for the treatment of adult patients with previously untreated DLBCL, including in the EU, UK, Japan, Canada and China.
Polatuzumab vedotin in combination with R-CHP was recently added to the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 1, preferred regimen for first-line DLBCL. Polatuzumab vedotin in combination with bendamustine and Rituxan is currently approved in more than 80 countries worldwide for the treatment of adults with relapsed or refractory (R/R) DLBCL after one or more prior therapies, including in the U.S.
Genentech continues to explore areas of unmet need where polatuzumab vedotin has the potential to deliver additional benefit, including in ongoing studies investigating combinations of polatuzumab vedotin with the company’s CD20xCD3 T-cell engaging bispecific antibodies mosunetuzumab-axgb (Lunsumio® Genentech/Roche) or the glofitamab (RG6026), an investigational CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy.
Trials include the Phase 3 SUNMO study in combination with mosunetuzumab in patients with R/R DLBCL and the Phase 3 POLARGO study with Rituxan in combination with gemcitabine and oxaliplatin in patients with R/R DLBCL.
Note: * Polatuzumab vedotin is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.
A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Diffuse Large B-Cell Lymphoma (POLARIX) – NCT03274492
Highlights of prescribing information
Polatuzumab vedotin-piiq (Polivy®; Genentech/Roche)[Prescribing Information]
Mosunetuzumab-axgb (Lunsumio® Genentech/Roche)[Prescribing Information]
Approved indication in the United States
- Polatuzumab vedotin-piiq (Polivy®) is a prescription medicine used with other medicines (a rituximab product, cyclophosphamide, doxorubicin, and prednisone) as a first treatment for adults who have moderate to high risk diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL).
- Mosunetuzumab-axgb (Lunsumio®) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer.
 FDA approves polatuzumab vedotin-piiq for previously untreated diffuse large B-cell lymphoma, not otherwise specified, and high-grade B-cell lymphoma. Food and drug Administration. Online. Last accessed on April 19, 2023.
 Types of B-cell Lymphoma. Diffuse large B-cell lymphoma (DLBCL). American Cancer Society (ACS). Online. Last accesses on April 19, 2023.