CD19 as a Target in the Treatment of DLBCL - Episode 9

Frontline Therapy for R/R DLBCL: TAFA/LEN/R-CHOP

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Drs John M. Burke and Marin F. Xavier consider the potential utilization of tafasitamab plus lenalidomide plus R-CHOP chemotherapy vs R-CHOP chemotherapy alone as relapsed/refractory diffuse large B-cell lymphoma treatment.

Marin F. Xavier, MD: We talked a lot about the combo of immunomodulator plus anti-CD19. The nice thing about loncastuximab is that it’s antibody-drug conjugate therapy, so I believe the payload is an alkylator. We don’t have to do the oral therapy, so it’s a little more lean in that respect. They’re priced pretty similarly in total cost. But there’s something about combining anti-CD19 with chemotherapy. We do expect synergy maybe with R [rituximab]–chemotherapy. There’s a MIND frontline trial looking at that, right?

John M. Burke, MD: I don’t know if there’s synergy between tafasitamab and chemotherapy. In fact, in the early days I was learning about tafasitamab, the key point was that there’s synergy with lenalidomide, but it wasn’t clear that there’s synergy with chemotherapy. I’m not sure anything has changed. It was thought that it’s important to give tafasitamab with lenalidomide because of the mechanism of tafasitamab improving ADCC [antibody-dependent cell cytotoxicity] and ADCT [antibody-drug conjugate toxicity] and the ability of lenalidomide to stimulate the T cells and the macrophages. That combination was thought to be synergistic in improving the cell kill, but I’m not sure the same is true with chemotherapy.

The phase 2 trial that got tafasitamab in the relapsed setting was L-MIND. A trial called First-MIND was done, which is a phase 1 trial that’s been reported at the last couple of meetings, not published yet. Patients were divided into 2 groups. There was tafasitamab plus R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and then tafasitamab-lenalidomide plus R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. That was a randomized trial. We’re learning about the outcomes. Suffice it to say, the responses look good. It’s a phase 1 trial, so you can’t compare response rates and efficacy outcomes with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], but it’s fair to say that responses look good. It does look to be a relatively tolerable regimen.

With the combo of tafasitamab-lenalidomide plus R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], there does appear to be increased thrombocytopenia compared with tafasitamab/R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. That was the 1 toxicity that was importantly a little more severe with the tafasitamab-lenalidomide combination. A few patients got platelet transfusions during the trial.

The general conclusion is that the combo of tafasitamab-lenalidomide and R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] is safe and appears to be effective. That arm has been taken forward to a frontline trial comparing tafasitamab-lenalidomide plus R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] alone. That trial has recently opened around the world. It’s recruiting patients with newly diagnosed DLBCL [diffuse large B-cell lymphoma] up to the age of 80 years. The trial is trying to select high-risk patients, so IPI [International Prognostic Index] 3 or higher. Some of the thought was that the many failed trials in the past might have been the high-performing control arm. That R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] performed better than expected because of relatively favorable-risk patients being treated on the control arm. This trial is attempting to select only the higher-risk IPI 3+ patients. It’s open, and it’s an international study.

Transcript edited for clarity.