The role of CAR-T cell therapy as second line in diffuse large B-cell lymphoma

Abstract

For approximately three decades, autologous hematopoietic cell transplantation (auto-HCT) has been the standard of care for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after frontline therapy. This approach is limited due to the intensity of chemotherapy and the proportion of patients who relapse after auto-HCT. Since the approval of anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy and novel agents, the treatment paradigm for DLBCL has changed remarkably. Anti-CD19 CAR-T therapy was first approved for relapsed DLBCL after two or more previous lines of therapy with long-lasting responses, with over 50% of patients still alive at 5-year follow-up. Here, we discuss recent randomized phase 3 clinical trials using axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in the second-line therapy setting compared with the standard of care in transplant-eligible patients who have DLBCL R/R within 12 months of completing chemo-immunotherapy, potentially changing the treatment algorithm for DLBCL.

STAT6 mutations enriched at diffuse large B-cell lymphoma relapse reshape the tumor microenvironment

“…To this end, further investigation is warranted to determine if therapeutic resistance is associated with STAT6 D419 -induced microenvironmental remodeling. From a therapeutic angle, knowing how the tumor influences the surrounding immune cells is important, as cellular therapies, such as CAR-T [50,51], are being increasingly used to treat rrDLBCL. Future studies may examine if STAT6 mutations affect responses to these novel therapies, by using immunocompetent mouse models that allow for the careful dissection and manipulation of the TME.…”

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions

“…Three formulations of the chimeric antigen receptor T cell (CAR-T) therapy, axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel, have been approved by the FDA for the treatment of relapsed/refractory DLBCL patients ( 83 ). The ZUMA-7, BELINDA, and TRANSFORM phase 3 clinical trials showed significant efficacy of CAR-Ts in the second line of treatment, and challenged the second line standard of care (SOC) with autologous stem cell transplantation.…”