Levine Cancer Institute, Atrium Health

The annual European Hematology Association (EHA) conference was recently held in Frankfurt, Germany, in a hybrid online and offline format. As the largest international conference in the European hematology field, the EHA meeting covered a wide range of scientific topics, clinical and basic research, including benign and malignant hematology, discussing the latest developments in the field of hematology. At this EHA conference, a study (abstract S224) by the team of Professor Ryan Jacobs from the Atrium Health Levine Cancer Institute in the U.S. explored the value of TNB-486 (targeting CD19/CD3) in the treatment of relapsed/refractory follicular lymphoma and achieved impressive results. As a result, Oncology Frontier interviewed Professor Ryan Jacobs on-site for a detailed interpretation of the latest developments in the treatment of follicular lymphoma and diffuse large B-cell lymphoma.

Oncology Frontier: There’s research on the combination of bispecific antibodies + rituximab + lenalidomide (R2) for the treatment of follicular lymphoma. Can you discuss the prospects of this combined approach?

Indeed, this EHA meeting reported on the efficacy of this combination treatment for follicular lymphoma (FL), particularly the promising triplet of bispecific antibody Epcoritamab + lenalidomide + rituximab. Lenalidomide and rituximab (R2 regimen) may currently be the most accepted second-line treatment for FL. Recent data shows that while the progression-free survival (PFS) of the R2 regimen may be just over 2 years, the time to the next treatment is over 70 months. Therefore, the R2 regimen is already a very effective treatment. Adding a bispecific antibody can enhance the immune-mediated effect of lenalidomide, an immunomodulatory agent. Hence, this triplet regimen is rational and has indeed shown high overall response rates (ORR) and complete remission rates (CR).

Oncology Frontier:Your team’s oral research (S224) reported on the use of a new bispecific antibody, TNB-486, for the treatment of relapsed/refractory follicular lymphoma. Can you explain this study?

This was a Phase I first-in-human clinical trial. TNB-486 was registered for the treatment of different subtypes of non-Hodgkin’s lymphoma (NHL). This study reports on its efficacy in follicular lymphoma (FL) patients, particularly those receiving doses of ≥2.4mg. Although the FL patients in this study were relapsed or refractory and had received an average of three lines of treatment, a high overall efficacy was still observed. The complete remission rate (CR) for patients with a TNB dose of ≥2.4mg reached 91%, and this was just with monotherapy. TNB-486 presents exciting therapeutic progress, which was previously only achieved with CD20/CD3 bispecific antibodies such as Epcoritamab, Glofitamab, and Mosunetuzumab. For the treatment of diffuse large B-cell lymphoma (DLBCL), monoclonal antibodies targeting CD19 like Tafasitamab and anti-CD19 ADC like Loncastuximab tesirine have shown good results, but only for DLBCL. For FL, the only treatment that directly targets CD19 is CAR-T. Unfortunately, many FL patients are not eligible for CAR-T treatment, either due to geographical constraints, not being near a CAR-T treatment center, or other factors like financial issues. Therefore, we eagerly anticipate a bispecific antibody targeting CD19. TNB-486 (targeting CD19/CD3) has shown good monotherapy efficacy, excellent treatment tolerance, and there’s much excitement for combining it with other drugs. This is undoubtedly encouraging for FL patients who have relapsed after receiving multiple CD20 monoclonal antibody treatments.

Oncology Frontier:Antibody-drug conjugates (ADC) have shown remarkable efficacy in first-line treatment for diffuse large B-cell lymphoma (DLBCL) in recent years. Can you discuss this?

Polatuzumab vedotin has been approved by the FDA in the U.S. to be combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) for first-line treatment of DLBCL, replacing the R-CHOP regimen as the standard for patients with an IPI score of ≥2 with advanced DLBCL. The POLARIX study showed that compared head-to-head with R-CHOP, Pola-R-CHP improved the 2-year progression-free survival rate by 6%. Polatuzumab vedotin is an ADC that targets CD79b and is conjugated

with the cytotoxic MMAE payload. This is a huge advancement. Additionally, other CD79b-targeting ADCs have shown good efficacy in recent studies. This includes the newly developed Loncastuximab tesirine, which is also an ADC targeting CD79b. In the LOTIS-2 trial, patients who previously failed multiple treatments achieved good results, with an overall response rate (ORR) of 48.3%. This ADC presents a significant breakthrough in the treatment of DLBCL.