If CAR T-Cell Therapy Fails, How Effective Are Bispecific Antibodies for Large B-Cell Lymphoma?

CAR T-cell therapy has transformed the treatment landscape for relapsed/refractory B-cell lymphomas, including large B-cell lymphoma (LBCL). This innovative approach achieves long-lasting remission in about 30–40% of cases. However, for patients who do not respond or relapse after CAR T-cell therapy, treatment options remain limited.

How effective are bispecific antibodies following CAR T-cell therapy for these patients? 

Small trials investigating CD3-CD20 bispecific antibodies after CAR T-cell therapy for relapsed/refractory LBCL patients showed that about 40% of participants achieved complete responses. However, the short follow-up periods in these studies left questions about long-term outcomes. 

Megan Melody, MD, from the University of South Florida Tampa General Hospital Cancer Institute, spearheaded research efforts to assess the real-world impact of bispecific antibodies in LBCL patients whose CAR T-cell therapy was unsuccessful.

Watch Dr. Melody's interview or review the study’s key findings below to learn more about this research presented at the 2024 ASH conference. 

Real-World Research of Bispecific Antibodies After CAR T-Cell Therapy 

Dr. Melody’s study tracked 830 patients with relapsed/refractory B-cell lymphoma across 14 academic centers between 2015 and 2024.

Among the participants, 429 experienced CAR T-cell therapy failure. Of these, 64 received bispecific antibody treatment an average of 218 days after their first therapy failed. These patients typically underwent about four cycles of treatment with various bispecific antibodies, including:

• Epcoritamab (Epkinly, Genmab/AbbVie)
• Glofitamab (Columvi, Genentech)
• Mosunetuzumab (Lunsumio, Genentech)

In some cases, additional therapies were administered alongside the bispecific antibodies.

What Were The Study’s Results? 

The overall response rate to bispecific antibody treatment was 54%, with 33% of patients showing a full reduction of the number of cancer cells (complete response). About two-thirds of these patients remained in complete remission for approximately 400 days. 

These findings show slightly poorer outcomes than those reported in other clinical trials testing bispecific antibodies for large B-cell lymphoma. This is potentially because the majority of patients in those studies did not previously receive CAR T-cell therapy. This highlights the importance of collecting real-world data. 

Regarding longer-term outcomes in Dr. Melody’s study:

• Progression-free survival (PFS): Half of the patients treated lived for more than 145 days without their cancer worsening after starting bispecific antibody treatment.
• Overall survival (OS): Regardless of their response to treatment, the survival time for 50% of patients was longer than 227 days.

Severe side effects were uncommon. Most side effects were mild, with some patients experiencing cytokine release syndrome (an inflammatory reaction that causes symptoms like fever) and neurotoxicity (inflammation that affects the brain, leading to symptoms like confusion). 

Influential Factors on Survival

• Negative impact:
  • High levels of lactate dehydrogenase (LDH) at the start of treatment were linked to worse survival outcomes.
  • Patients with aggressive disease characteristics, such as double-hit lymphoma, or those who did not respond well to initial treatments or relapsed quickly after CAR T-cell therapy, also had poorer outcomes.
• Positive impact:
  • Patients who received bispecific antibodies as their first rescue treatment following CAR T-cell therapy failure experienced better progression-free survival compared to those who were treated later in the cancer course.

Future Directions

Bispecific antibodies represent a promising treatment option for patients with relapsed/refractory aggressive B-cell lymphoma if CAR T-cell therapy fails. Ongoing research will continue to refine the use of bispecific antibodies, optimize patient outcomes, and potentially expand their role in the lymphoma treatment landscape, ensuring that more patients benefit from these innovative therapies earlier in the cancer course.

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Sources: 

• Efficacy, Toxicity, and Predictors of Outcomes with CD3-CD20 Bi-Specific Antibodies Post CAR T-Cell Failure for Aggressive B-Cell Lymphoma
• Bispecific Antibody Use After CAR-T Failure for B-Cell Lymphoma