Dr Nowakowski on the Current Treatment Landscape for DLBCL

Grzegorz S. Nowakowski, MD, consultant, Division of Hematology; enterprise deputy director, Clinical Research, Mayo Clinic Comprehensive Cancer Center, discusses the current treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), emphasizing the need for novel therapeutic approaches to treat patients in the second-line setting.

Standard frontline therapy for DLBCL typically involves chemoimmunotherapy regimens, such as R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone), which has been associated with an overall response rate of approximately 80% to 90%, Nowakowski explains, adding that approximately 60% to 70% of patients can achieve complete remission. Despite these high initial response rates, a proportion of patients will still experience disease relapse, including many within the first 2 years of initiating treatment. For the approximately 40% of patients with DLBCL who experienced relapse following frontline chemoimmunotherapy, the prognosis is often poor with limited long-term survival, Nowakowski explains.

Nowakowski notes an existing need to continue developing novel treatments for patients in the second line and beyond, particularly for those who do not achieve durable remission with standard chemoimmunotherapy. Current therapeutic developments are focusing on the integration of novel agents, including CAR T-cell therapies, targeted therpies, and bispecific antibodies.

Approved CAR T-cell therapies, such as axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah) have emerged as later-line options for patients with relapsed/refractory DLBCL. Notably, axi-cel’s initial approval came in the third-line setting in 2017 before the indication was updated to include second-line treatment in 2022.

Additionally, bispecific antibodies such as glofitamab-gxbm (Columvi) and epcoritamab-bysp (Epkinly) targeting CD20-positive B cells offer another treatment avenue for relapsed/refracotry DLBCL.

Nowakowski concludes by explaining that the continued development of these novel therapies is essential to address the unmet needs in DLBCL, particularly for patients who relapse after frontline treatment.