Two-year progression free survival (PFS) was 76.7% for the 440 patients randomized to polatuzumab-vedotin (PV) add-on, versus 70.2% for the 439 randomized to R-CHOP, which translated to a 27% reduction in the risk of progression, relapse, or death (P = .02). However, overall survival (OS) at 2 years was just under 89% in both arms of the trial, dubbed POLARIX. Toxicity was comparable between the two arms.
The investigators swapped out the vincristine in R-CHOP for PV to avoid overlapping neurotoxic side effects and called their modified regimen “pola-R-CHP.”
“We believe these results support use of pola-R-CHP in the initial management of patients with DLBCL,” senior investigator Gilles Salles, MD, PhD, a hematologic oncologist at Memorial Sloan Cancer Center in New York, said at the American Society of Hematology annual meeting.
The study (ASH 2021 abstract LBA-1), was published simultaneously in the New England Journal of Medicine.
Worth the cost?
The investigators reported that the median follow up of 28.2 months may simply have been too short to see if the PFS benefit translates into better overall survival. Also, newer treatments for relapsed/refractory disease might have masked any OS benefit.
With the PFS benefit, however, “what we think we are seeing is a deeper, more profound complete remission that hopefully will translate into [better] overall survival, but it may be a while until that can be demonstrated,” said Jane N. Winter, MD, a hematologic oncologist at Northwestern University, Chicago, who moderated Dr. Salles’ presentation.
“If the improvement in PFS at 2 years represents a true higher cure rate and plateau rather than a simple delay in relapse,” the “results from the POLARIX trial are likely to be practice-changing,” blood cancer specialist Ajay K. Gopal, MD, professor of medicine at the University of Washington, Seattle, told this news organization when asked for comment.
With additional OS results pending, an audience member at ASH wondered if “the cost of this highly expensive monoclonal antibody drug conjugate is worth the small improvement in PFS.”
“We have to further study this point, but at this moment what is important is to have a treatment with better efficacy and no more toxicity” than R-CHOP, lead investigator Herve Tilly, MD, a hematologic oncologist at the University of Rouen, France, said at the meeting.
Dr. Gopal said the cost concerns are legitimate, but also pointed out that they “may be somewhat offset by the potential reduction in downstream use of expensive cellular therapies.”
The findings support his assertion. With reduced PFS, R-CHOP subjects were more likely than were pola-R-CHP subjects to go on to subsequent lines of therapy (30.3% versus 22.5%).
PV is already approved in the United States for relapsed or refractory DLBCL in combination with bendamustine and rituximab after failure of at least two previous regimens.