Challenges in the management and treatment of patients with relapsed/refractory DLBCL

The virtual Lymphoma Hub Satellite Symposium at the European School of Haematology (ESH)’s 2nd How to Diagnose and Treat: Lymphoma conference saw a panel of international experts come together to discuss how to manage patients with relapsed and/or refractory (R/R) lymphoma. Kieron Dunleavy, George Washington University Cancer Center, Washington, US, and Marie José Kersten, Amsterdam UMC, Amsterdam, NL, discussed the progress being made in the field of R/R diffuse large B-cell lymphoma (DLBCL). Below you will find their perspectives as presented at the symposium.

Patient case

The two panelists outlined their approaches to treating a distinct patient case (Figure 1) while highlighting the emerging strategies in the R/R DLBCL setting across Europe and the US.

ASCT, autologous hematopoietic stem cell transplantation; CAR, chimeric antigen receptor; DHAP, dexamethasone + high-dose cytarabine + cisplatin; DLBCL, diffuse large B-cell lymphoma; ECOG, FISH, fluorescence in situ hybridization; IGHV, immunoglobulin heavy chain variable region; LDH, lactate dehydrogenase; R/R, relapsed and/or refractory; R-CHOP, rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone. 

US perspective: Kieron Dunleavy

Kieron Dunleavy began with a summary of what he considers to be feasible next steps for the patient following relapse to chimeric antigen receptor (CAR) T-cell therapy. He outlined recently approved agents and combination regimens, as well as therapies being evaluated in clinical trials. Dunleavy concluded with an emphasis on prognostic techniques, stressing the need for a biopsy to determine the patient’s CD19 expression profile. In terms of therapeutic approach, he suggested enrolling the patient onto a clinical trial evaluating novel bispecific antibodies.

Take part in the survey and watch Kieron Dunleavy’s presentation below.

European perspective: Marie José Kersten

Marie José Kersten opened with a comprehensive overview of the pivotal clinical trials evaluating CAR T-cell treatments for DLBCL. She then moved on to explain the most widely understood mechanisms of resistance to CD19-directed CAR T-cell therapy. This introduction helped to paint a clearer picture of the patient case, explaining why a proportion of patients who receive CAR T-cell therapy eventually relapse. Marie José Kersten highlighted the potential benefit of a second infusion of CAR T cells, as was investigated in a cohort of patients from the ZUMA-1 study.

After outlining a number of novel CAR T constructs, she proceeded to discuss non-CAR T-based therapies and relevant clinical trial opportunities for the patient. These included studies evaluating bispecific antibodies, including epcoritamab and blinatumomab, and the CDK9 inhibitor AZD4573.

Kersten also pointed out the discrepancies in access to novel drugs between the US and Europe, and the inter-country variations within Europe.

Watch Marie José Kersten’s presentation below.

Conclusion

Despite the encouraging clinical outcomes demonstrated by CAR T-cell therapies in patients with DLBCL, a proportion of patients do not respond to CAR T-cell therapy, or eventually relapse, as in the selected patient case. There are a number of exciting novel agents in clinical trials that promise to improve the outlook of patients with heavily pretreated DLBCL. Both panelists were in consensus that participation in clinical trials is the optimal approach for managing patients who have exhausted other treatment strategies, including CAR T-cell therapy.