Adding the investigational treatment polatuzumab vedotin to a therapy of Bendeka (bendamustine) and Rituxan (rituximab) made patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) respond better to the treatment.
The clinical trial investigating the treatment also indicated that the triple-combination allowed patients to survive longer.
Genentech will present data from the Phase 1b/2 trial that investigated the treatment combination at the upcoming 59th American Society of Hematology (ASH) Annual Meeting Dec. 9-12 in Atlanta, Georgia.
The findings have already led to the compound being granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration. It has also received PRIME (PRIority MEdicines) designation in the European Union.
The meeting presentation is titled, “Addition of Polatuzumab Vedotin to Bendamustine and Rituximab (BR) Improves Outcomes in Transplant-Ineligible Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) Versus BR Alone: Results from a Randomized Phase 2 Study.”
The Phase 1b/2 trial (NCT02257567) included 78 patients in the Phase 2 part who were ineligible for stem cell transplants. They were randomly assigned to treatment with Bendeka and Rituxan with or without polatuzumab vedotin.
More patients in the triple combination group responded to the treatment — 70 percent compared to only 33 percent in the Bendeka-Rituxan group. The addition of polatuzumab vedotin also improved complete response rates from 20 percent in the Bendeka-Rituxan group to 58 percent.
The duration of response was also better in patients on polatuzumab vedotin. Half of these patients had an ongoing response for at least 8.8 months, compared to a median of only 3.7 months in the double-combo group.
The study was too small to provide robust assessments of survival, but researchers said the data demonstrated significant survival differences between the groups.
Patients on polatuzumab vedotin survived without disease progression for a median of 6.7 months, compared to only two months in the Bendeka-Rituxan group.
Meanwhile, overall survival was 11.8 months in the triple-combo and 4.7 months in the double-combo group — lowering the risk of death during the study by 65 percent, compared to the Bendeka-Rituxan treatment.
At one year, 48 percent of patients on the triple combo with polatuzumab vedotin were still alive, compared to 24 percent in the double-combo group.
While achieving such results, the treatment did not give rise to unmanageable safety issues, researchers said. But it did cause more side effects than the dual combination with Bendeka and Rituxan.
The addition of polatuzumab vedotin lowered blood cell counts more than the double combo and was more often linked to diarrhea, fatigue, fever, a loss of appetite, rash, and infusion-related reactions.
It also caused symptoms from peripheral nerves far more often — 39 percent of patients in the polatuzumab vedotin group developed peripheral neuropathy, compared to only 3 percent in the control group.
Rates of infections, nausea, and constipation were similar in the two groups.
One-third of patients in the triple-combination group quit the treatment early because of adverse events, compared to 10 percent in the Bendeka-Rituxan group.
Polatuzumab vedotin is an antibody-drug conjugate that targets the CD79b protein — a molecule found on the surface of the majority of cancerous B-cells.
“Our ongoing development program in hematology is one of the largest in this area, underscoring our commitment to developing practice-changing medicines and improving outcomes for people with diseases of the blood,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a press release.
