Adding polatuzumab vedotin (an antibodydrug conjugate targeting CD79b-positive cells) to the combination of bendamustine and rituximab (BR) extended survival and increased complete responses (CRs) in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL), according to results from a phase II trial presented at the 23rd Congress of the European Hematology Association.
These improvements were seen with “acceptable toxicity” compared with BR alone, the researchers, led by Laurie Sehn, MD, from the BC Cancer Agency in Vancouver, British Columbia, Canada, reported.
The study included transplant-ineligible patients with follicular lymphoma (FL; n=80) and DLBCL (n=80). All participants were randomized to receive intravenous bendamustine 90 mg/m2 and rituximab 375 mg/m2 alone (n=41 in FL and n=40 in DLBCL), or with polatuzumab vedotin 1.8 mg/kg (n=39 in FL; n=40 in DLBCL). In the FL group, treatment was administered in six 28-day cycles; in the DLBCL group, treatment was administered in six 21-day cycles.
An independent review committee assessed CR (using the modified Lugano criteria) as determined by PET scan approximately six to eight weeks following treatment (primary endpoint).
In the FL cohort, median age was 65 years and 63 years (ranges not reported) in the polatuzumab vedotin and BR-alone groups, respectively. Forty-one percent and 42 percent, respectively, were refractory to last therapy and the median number of prior therapies was two (range not reported).
In the DLBCL cohort, median age was 67 years and 71 years (ranges not reported) in the polatuzumab vedotin and BR-alone groups, respectively. Twentynine percent and 32 percent, respectively, were refractory to their last therapy and, again, the median number of prior therapies was two (range not reported).
In her presentation, Dr. Sehn highlighted the grade 3-5 adverse events (AEs) that occurred more frequently in the polatuzumab vedotin groups, compared with BR alone: cytopenias and febrile neutropenia in both disease groups and infections in the FL group. Grade 5 AEs appeared to occur more frequently in the FL group (5% in FL and 18% in DLBCL).
“There were no unexpected toxicities [with the polatuzumab vedotin combination], so it was typical for what we would expect with what is known with this drug alone and BR alone,” Dr. Sehn said.
At a median follow-up of 15 months (range not reported), rates of progressionfree survival (PFS) and PET-confirmed CR were similar among patients in the FL group. However, in the DLBCL group, the addition of polatuzumab vedotin to BR significantly increased all efficacy outcomes: PET-CR (p=0.012), median PFS (p<0.0001), and median overall survival (OS; p=0.0008; see TABLE).
The researchers also observed apparent differences in PFS and OS in patients with DLBCL receiving polatuzumab vedotin versus BR alone, regardless of patients’ prior treatment or disease status (p values not reported):
- secondline therapy (PFS: 11.1 months vs. 3.7 months; OS: not reached for either)
- thirdline plus therapy (PFS: 6.0 months vs. 2.0 months; OS: 11.5 months vs. 3.8 months)
- relapsed disease (PFS: 11.1 months vs. 5.1 months; OS: not reached for either)
- refractory disease (PFS: 6.0 months vs. 1.9 months; OS: 11.5 months vs. 3.8 months)
Also, the addition of polatuzumab vedotin appeared to result in greater OS in thirdline plus therapy (11.5 months vs. 3.8 months) and refractory patients (11.5 months vs. 3.8 months) compared with bendamustine and rituximab only, though p values were not reported.
Dr. Sehn noted a potential limitation of this head-to-head study is that “time-to-event endpoints are immature due to low event rate.” Based on the results reported in this trial for both DLBCL and FL cohorts, polatuzumab vedotin has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and is being explored in other combinations in ongoing trials, she added.
Dr. Sehn reports a financial relationship with Roche, the manufacturer of polatuzumab vedotin.
Sehn LH, Kamdar M, Herrera AF, et al. Adding polatuzumab vedotin (POLA) to bendamustine and rituximab (BR) treatment improves survival in patients with relapsed/refractory DLBCL: results of a phase 2 clinical trial. Abstract #S802. Presented at the 23rd Congress of the European Hematology Association, June 16, 2018; Stockholm, Sweden.