DLBCL Management With Combination Therapy in the Relapsed/Refractory Setting

Polatuzumab Shows Improved Survival and Complete Responses in R/R DLBCL

Ian W. Flinn, MD, PhD, discusses the study design and results of the phase 2 trial of the antibody-drug conjugate polatuzumab vedotin-piiq plus bendamustine and rituximab for patients with relapsed/refractory diffuse large B-cell lymphoma.

Ian W. Flinn, MD, PhD, director of lymphoma research at Sarah Cannon Cancer Institute, discusses the study design and results of the phase 2 trial (NCT02257567) of the antibody-drug conjugate polatuzumab vedotin-piiq (Polivy) plus bendamustine and rituximab (Rituxan) for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

In cohorts C and D of this trial, 80 patients were randomized 1:1 to receive either 1.8 mg/kg of polatuzumab every 3 weeks plus bendamustine and rituximab for 6 cycles, or only bendamustine and rituximab. The primary end point was complete response (CR) rate as assessed by an independent review committee.

The primary end point was met, with a CR rate in the polatuzumab arm of 40%, versus 17.5% in those receiving only bendamustine/rituximab. At a median follow-up of 22.3 months, the polatuzumab arm had a median progression-free survival (PFS) of 9.5 months versus 3.7 months in the other arm (HR, 0.36; 95% CI, 0.21-0.63; P < .001). Median overall survival (OS) was 12.4 months with polatuzumab versus 4.7 months with only bendamustine/rituximab (HR, 0.42; 95% CI, 0.24-0.75; P = .002).

Flinn says these are impressive results considering that patients had a median of 2 prior lines of therapy. This trial led to the approval of polatuzumab vedotin plus bendamustine/rituximab as third-line therapy for R/R DLBCL.

TRANSCRIPTION:

0:08 | This was the study of polatuzumab vedotin with bendamustine and rituximab. There are several different arms of this trial, but the pivotal arm was a randomized phase 2 trial that had a 1:1 randomization for patients who had previously treated DLBCL that had relapsed/refractory patients. There were 80 patients on this trial; patients are randomized 1:1 to receive [bendamustine/rituximab] plus or minus polatuzumab. And the primary end point of this study was CR rate.

0:45 | The basic results of this study were that 40% of patients achieved a CR rate with a CR with polatuzumab/BR versus 17.5% of patients who are on the [bendamustine/rituximab]-alone arm, and…that met the primary end point of the study which was a higher CR rate as judged by an independent response committee. The other end points of the study were PFS and OS. And there was a substantial improvement in PFS for those patients treated on the experimental arm, it was 9.5 months versus 3.7 months.

1:29 | And then the OS was also surprisingly much improved with those patients who received the polatuzumab-containing arm. I say surprisingly, because this was third line, and the magnitude of difference was pretty large; it was 12.4 months versus 4.7 months. And when you think about it, this is not very many patients, just 40 patients per arm. To me, this was very spectacular results.