Sequencing of therapy for patients with diffuse large B-cell lymphoma in the era of novel drugs

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma, accounting for ~40% of all cases in adults. Whilst approximately two-thirds of DLBCL patients can be cured by first-line therapy, one-third of patients are primary refractory or relapse after an initial response (r/r DLBCL). Recent advances in the treatment of DLBCL have been achieved by a plethora of novel drugs, such as monoclonal antibodies, antibody-drug conjugates (ADC), bi-specific T-cell engagers (BITEs), and CD-19 directed chimeric antigen receptor (CAR)-T-cell therapies. The increasing number of therapeutic options significantly improved the outcome of patients; however, the therapeutic algorithm has become increasingly complex. In this review, we provide an overview of novel therapies for DLBCL patients and potential treatment sequencing from first to second, third, and later lines.

Keywords: DLBCL; antibody‐drug conjugate (ADC); bi‐specific T‐cell engager (BITE); chimeric antigen receptor (CAR)‐T‐cell therapy; high‐dose chemotherapy/autologous stem cell transplantation (HDCT/ASCT); novel drugs; sequencing therapies.

FIGURE 1

Potential therapeutic algorithm for patients with DLBCL. ADC, antibody–drug conjugate; allo‐SCT, allogeneic stem cell transplantation; BITEs, bi‐specific T‐cell engagers; CAR‐T, chimeric antigen receptor T‐cell therapy; DLBCL, diffuse large B‐cell lymphoma; HDCT/ASCT, high‐dose therapy and autologous stem cell transplantation; IPI, International Prognostic Index; mo., months; Pola‐BR, polatuzumab–vedotin, bendamustine, rituximab; Pola‐R‐CHP, polatuzumab–vedotin, rituximab, cyclophosphamide, doxorubicin, prednisone; R, rituximab; R‐CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R‐GemOx, rituximab, gemcitabine, oxaliplatin.