Ian W. Flinn, MD, PhD

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; 

 < .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; 

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.

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.

 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.

 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.

Videos

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. 

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

Ian W. Flinn, MD, PhD, director of lymphoma research and a principal investigator at Sarah Cannon Research Institute, and director of the Sarah Cannon Center for Blood Cancer at Tennessee Oncology and TriStar Centennial Medical Center, discusses the Bruton’s kinase (BTK) inhibitors available for patients with B-cell malignancies and how they compare.

There are many ongoing trials with zanubrutinib (Brukinsa) and other BTK inhibitors in the B-cell lymphoma landscape. Flinn says the biggest issue in these disease settings currently is deciding which BTK inhibitor is better to use for these patients. Head-to-head trials are looking at zanubrutinib with ibrutinib (Imbruvica) versus acalabrutinib (Calquence) with ibrutinib to get a better understanding of how the efficacy and adverse event profiles compare.

Many people think that these drugs are fairly similar in their efficacy, but because some patients have to come off treatment—most prominently with ibrutinib—that cuts into the efficacy because patients are no longer on therapy, according to Flinn. He thinks that may be where the differences are most evident for patients and will help physicians decide which BTK inhibitor is best to use depending on the patient.

<< View more resources and information regarding hematology

Ian W. Flinn, MD, PhD, discusses the Bruton’s kinase inhibitors available for patients with B-cell malignancies and how they compare.

Comparing BTK Inhibitors in Patients With B-Cell Malignancies

Articles

Ian W. Flinn, MD, PhD, director, Blood Cancer Research Program, principal investigator, Sarah Cannon Research Institute, discusses a phase I story which examined cerdulatinib in patients with relapsed/refractory B-cell malignancies.

Cerdulatinib in Relapsed/Refractory B-Cell Malignancies

Ian W. Flinn, MD, PhD, director, Hematologic Malignancies Research Program, Sarah Cannon Research Institute, discusses the mechanism of action and toxicity profile of duvelisib (IPI-145). Duvelisib is being studied for the treatment of hematologic malignancies.

Duvelisib inhibits both delta and gamma isoform.

The hope is that the molecule targets both the tumor cell as well as the microenvironment.

The toxicity profile of duvelisib is still being studied.

To date, the molecule appears to have a similar toxicity profile of other PI3K inhibitors.

Ian W. Flinn, MD, PhD, discusses the mechanism of action and toxicity profile of duvelisib (IPI-145). Duvelisib is being studied for the treatment of hematologic malignancies.

The Mechanism of Action and Toxicity Profile of Duvelisib (IPI-145)

Ian W. Flinn, MD, PhD, director, Hematologic Malignancies Research Program, Sarah Cannon Research Institute, gives an overview of two ongoing clinical trials looking at IPI-145 for the treatment of hematologic malignancies.

- DUO is a randomized, phase III trial comparing IPI-145 to ofatumumab for patients with relapsed or refractory CLL or SLL.

- Ofatumumab is a CD20-directed cytolytic monoclonal antibody approved for the treatment of CLL.

- Patients in this trial are randomized 1:1 and are able to cross over.

- DYNAMO is a single-arm, phase II trial of patients with non-Hodgkin lymphoma that are no longer responding to rituximab or chemotherapy.

- There is currently no established therapy for this group of patients.

View more from the 2014 ASCO Annual Meeting

Ian W. Flinn, MD, PhD | Authors

Articles

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

Comparing BTK Inhibitors in Patients With B-Cell Malignancies

Cerdulatinib in Relapsed/Refractory B-Cell Malignancies

The Mechanism of Action and Toxicity Profile of Duvelisib (IPI-145)

Two Ongoing Clinical Trials of IPI-145 for Hematologic Malignancies