Management Considerations for Patients With Primary Refractory and Early Relapsed Diffuse Large B-Cell Lymphoma

Area of Science:

• Hematology
• Oncology
• Immunotherapy

Background:

• Diffuse large B-cell lymphoma (DLBCL) has a significant relapse rate despite initial chemoimmunotherapy.
• Traditional salvage chemotherapy followed by autologous stem-cell transplant (ASCT) is less effective for high-risk relapsed/refractory (R/R) DLBCL.
• Advancements in cellular therapies are transforming R/R DLBCL treatment paradigms.

Purpose of the Study:

• To review the current treatment landscape for R/R DLBCL.
• To evaluate the role of CAR T-cell therapy as a second-line treatment option.
• To provide recommendations for managing R/R DLBCL based on patient fitness and disease characteristics.

Main Methods:

• Review of clinical trial data (e.g., TRANSFORM, ZUMA-7, PILOT) for CAR T-cell therapies.
• Analysis of treatment outcomes for R/R DLBCL patients.
• Synthesis of current guidelines and expert recommendations for R/R DLBCL management.

Main Results:

• Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are approved second-line therapies for high-risk R/R DLBCL in medically fit patients.
• Liso-cel is a viable option for R/R DLBCL patients who are transplant-ineligible.
• CAR T-cell therapy demonstrates positive outcomes and manageable toxicity profiles.

Conclusions:

• CAR T-cell therapies (axi-cel or liso-cel) are recommended as second-line treatments for fit R/R DLBCL patients.
• Liso-cel is recommended for unfit R/R DLBCL patients.
• Alternative strategies including ASCT, clinical trials, and other emerging therapies should be considered when CAR T-cell therapy is not feasible.