Should CAR-T cell therapy be considered a standard of care for patients with refractory diffuse large B-cell lymphoma in second line treatment?

in Expert opinion on biological therapy by Lucia Perez-Lamas, Jose Sandoval-Sus, Julio C Chavez

TLDR

  • CAR-T therapy demonstrated superior outcomes compared to historical standard chemoimmunotherapy and consolidation with auto-HCT in phase 3 trials.
  • Phase 2 trials showed the efficacy of CAR-T therapy in patients ineligible for auto-HCT.
  • The study highlights the need to define patient populations and enhance accessibility and cost-effectiveness to expand CAR-T therapy in earlier treatment lines.

Abstract

CAR-T therapy has transformed the treatment landscape for relapsed/refractory diffuse large B-cell lymphomas (DLBCL). This article reviews the existing evidence for using CAR-T therapy as a second-line treatment. Two major phase 3 trials, ZUMA-7 and TRANSFORM, have shown that axi-cel and liso-cel, respectively, offer superior outcomes compared to historical standard chemoimmunotherapy and consolidation with autologous hematopoietic stem cell transplantation (auto-HCT). Additionally, two promising phase 2 trials, PILOT and ALYCANTE, demonstrated the efficacy of CAR-T therapy in patients who are ineligible for auto-HCT. We also reviewed the potential biological factors behind these results. Several factors support the use of CAR-T therapy in earlier treatment lines: better T-cell fitness in the infused product, reduced systemic inflammation in patients, and a more favorable tumor microenvironment. Although real-world data for second-line CAR-T therapy is still early, it is expected that CAR-T will be used more widely. Additional focus highlights the need for defining suitable patient populations and the efforts to enhance accessibility and cost-effectiveness of this groundbreaking treatment approach.

Overview

  • This study reviews the existing evidence for using CAR-T therapy as a second-line treatment for relapsed/refractory diffuse large B-cell lymphomas (DLBCL).
  • Two major phase 3 trials, ZUMA-7 and TRANSFORM, have shown that axi-cel and liso-cel, respectively, offer superior outcomes compared to historical standard chemoimmunotherapy and consolidation with autologous hematopoietic stem cell transplantation (auto-HCT).
  • The study highlights the need for defining suitable patient populations, enhancing accessibility, and cost-effectiveness of CAR-T therapy to expand its use in earlier treatment lines.

Comparative Analysis & Findings

  • Two phase 3 trials, ZUMA-7 and TRANSFORM, demonstrated superior outcomes for axi-cel and liso-cel, respectively, compared to historical standard chemoimmunotherapy and consolidation with auto-HCT.
  • Two phase 2 trials, PILOT and ALYCANTE, showed the efficacy of CAR-T therapy in patients who are ineligible for auto-HCT.
  • Biological factors supporting the use of CAR-T therapy in earlier treatment lines include better T-cell fitness, reduced systemic inflammation, and a more favorable tumor microenvironment.

Implications and Future Directions

  • The study supports the expanded use of CAR-T therapy in earlier treatment lines due to its superior outcomes and promising results in phase 2 trials.
  • Defining suitable patient populations and enhancing accessibility and cost-effectiveness are crucial to increase the adoption of CAR-T therapy.
  • Real-world data and ongoing research will provide further insights on the long-term efficacy and safety of CAR-T therapy in second-line treatment.
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