Future Use of Novel Therapy in DLBCL

Matthew J. Matasar, MD:As we continue to explore the best ways to leverage polatuzumab vedotin-[piiq] into diffuse large B-cell lymphoma, we look at the current FDA approval in the NCCN [National Comprehensive Cancer Network] Compendium Listing, which is third-line plus. Despite the fact that the GO29365 study enrolled both second- and third-line patients, it was decided that the relative paucity of patients in the second-line setting was not enough to justify approval or compendium listing for such patients. This is despite the fact that the outcomes for second-line patients were actually better in this small group of patients than for third-line plus.

Given that there’s work ongoing to better explore the activity of polatuzumab for second-line patients, additionally given that BR [bendamustine, rituximab] is not universally accepted as the preferred regimen for relapsed-refractory large-cell lymphoma for transplant-ineligible patients, and despite the fact that there are no great data that 1 regimen is better than the other, many clinicians in this area prefer regimens like R-GemOx [rituximab, gemcitabine, oxaliplatin] for such patients. There is currently a study opening that is a randomized trial of R-GemOx [rituximab, gemcitabine, oxaliplatin] plus or minus polatuzumab for second-line-plus patients who are transplant ineligible.

This is an important study for a couple of reasons. First, we’ll gain a clear understanding for its activity and role in second-line patients. We’ll also have a better sense for whether adding it to a platinum-based backbone, No. 1, continues to show incremental benefit from inclusion of polatuzumab; as well as whether there is or is not an increased risk of neurotoxicity when combining polatuzumab with a platinum-based program.

Additionally, we have the POLARIX trial, which was a recently concluded randomized clinical trial that was conducted worldwide in newly diagnosed diffuse large B-cell lymphoma with an IPI [International Prognostic Index] score of 1 or more. This was a randomized trial of R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone] versus R-CHP [rituximab, cyclophosphamide, doxorubicin hydrochloride, prednisone], with substitution of vincristine with polatuzumab vedotin in a 1:1 randomized fashion. This was a randomized and double-blinded placebo-controlled trial with a primary end point for overall survival as its end point with ORR [objective response rate], CR [complete response], and other quality-of-life end points as important as secondary end points.

This trial is now done, and we hope to have readout from this trial, probably, by the year 2021. If this trial is positive, if it does show an overall survival benefit in newly diagnosed diffuse large B-cell lymphoma, it would be the first randomized trial to demonstrate a superiority over R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone]. Secondly, it would likely represent a new standard of care in such patients.

The therapeutic landscape for relapsed-refractory large-cell lymphoma continues to change rapidly. There’s a lot of work being done in multiple areas. There’s a lot of work being done in immunotherapy as we continue to develop and enhance our use of CAR [chimeric antigen receptor] T-cell therapy. There’s the field of bispecific antibodies. These are antibodies that bind to both the B-cell antigen as well a T-cell antigen, such as CD3, and serve as a potent stimulus for T-cell activation and proliferation. A number of targeted therapies are being developed trying to attack either individually or via combination therapy, multiple signaling pathways within the malignant B-cell.

There’s a lot of active research going on at Memorial Sloan Kettering Cancer Center [in New York, New York], around the country and around the world, to treat relapsed-refractory large-cell lymphoma. This remains an area of tremendous unmet need and an area in which we need to continue to do better for our patients.

Transcript edited for clarity.