 We talked about polatuzumab moving to the front. Let’s talk about tafasitamab. There’s tafasitamab lenalidomide or tafasitamab alone. Dr Wang, what are your thoughts about potentially moving tafasitamab to an earlier in the line of therapy?

It’s happening as we speak. We just learned from the L-MIND trial that if you use the drug earlier, you have a better and more durable response and better survival. So moving the L-MIND regimen to the front line makes sense. To do that, we needed to approve the safety and feasibility. The First-MIND trial mainly tested the feasibility of adding tafasitamab to R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] or tafasitamab and lenalidomide to R-CHOP. The study was presented at ASH [American Society of Hematology Annual Meeting], and it showed a high response rate, with very promising early progression-free survival data. More important, the safety data look very good, and there’s nothing surprising when you add tafasitamab-lenalidomide to R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. Based on those data, the frontline trial randomizing tafasitamab-lenalidomide plus R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] vs R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] alone has accrued already. We’re eager to see those data in a year or 2.

 That will be in the front of our mind. We heard about tafasitamab. CAR [chimeric antigen receptor] T-cells based on ZUMA-7 have an overall survival [OS] advantage. That’s already tickled a lot of neurons, and now we’re into the double digits in the ZUMA trials. We heard about ZUMA-12 even earlier in an enriched population, but ZUMA-12 wasn’t the last stop for ZUMA. We’re at the ZUMA-23 now. Dr Westin, can you talk about ZUMA-23?

 ZUMA-23 is a randomized global phase 3 study in frontline patients with high-risk disease. We saw that second-line axicabtagene-ciloleucel was superior in and EFS [event-free survival] and OS, so why not move that to the front line to evaluate the highest-risk patients before chemotherapy resistance or refractory disease emerges? The filters for ZUMA-23 are in IPI [International Prognostic Index] of 4 or 5; that’s at diagnosis. Patients with DLBCL [diffuse large B-cell lymphoma] and OS, high-grade B-cell lymphoma, and transformed disease who haven’t had a prior anthracycline could all be eligible. Everybody gets 1 cycle of R [rituximab]–chemotherapy prior to going on trial. Then you’re eligible, and your randomized to stay the course—finishing your 6 cycles of R [rituximab] chemotherapy, which on this trial is R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] or R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, hydroxydaunorubicin hydrochloride]—or axicabtagene-ciloleucel arm. This would have apheresis followed by a second cycle of R [rituximab] chemotherapy to hold the disease while you’re waiting for manufacturing. This keeps the cadence of every-3-week therapy, which is the paradigm in front line. The study is up and rolling, and it’s a global study. We’re eagerly anticipating those results, but it’s going to take a few years to enroll that high-risk-patient population across the globe.

 Can you be treated at an outside institution and be referred in at cycle 2 for the study?

 Absolutely. That first cycle is outside the protocol, so this is an intentional strategy to get the highest-risk patients. Many studies have lots of barriers to get on the trial. You need a central review of radiology and a biopsy review to confirm pathology. All those delays in time mean that the sickest patients can’t wait, and they go and do something else. We’ve seen many studies where they’re randomized, but the control arm seems to do better than you’d expect, probably because those sickest patients could not get on trial. ZUMA-23 is mandating 1 cycle of therapy before you go on trial, and that will allow many patients who aren’t at a CAR T-cell center, but who have bad disease, to get to the CAR T-cell center and then perhaps participate in the study.

 That’s another exciting trial—for future discussions.

Videos

Expert perspectives on recent efforts to move novel therapy from the relapsed/refractory to frontline setting of diffuse large B-cell lymphoma.

Jason Westin, MD, The University of Texas MD Anderson Cancer Center

Articles

Diffuse Large B-Cell Lymphoma: Moving Novel Therapy to the Frontline Setting