Is Odronextamab Effective if CAR-T Stops Working for DLBCL?

Learn how a new bispecific antibody called odronextamab (by Regeneron) is showing promise in a clinical trial for people with diffuse large B-cell lymphoma (DLBCL) whose CAR T-cell therapy has stopped working. 

Why might bispecific antibodies be needed after CAR T-cell therapy? 

For about half of DLBCL patients, CD19-targeted CAR T-cell therapy stops working within six months. Additionally, up to 35% of these patients don’t receive further treatment, highlighting the need for new options if CAR-T doesn’t work.

One reason CAR T-cell therapy fails is that cancer cells lose or change the CD19 protein, making them invisible to the treatment. While CAR T-cells can sometimes be reengineered, bispecific antibodies like odronextamab already offer another approach.

Odronextamab binds to CD20 on lymphoma cells and CD3 on T-cells, bringing them together so the immune system can attack. Because it targets CD20, not CD19, odronextamab can still find and fight lymphoma cells even when CD19 is missing.

Bispecific antibodies are also “off-the-shelf” treatments, meaning they don’t require customization from a patient’s cells like CAR-T, making them more accessible. 

What did the ELM-1 study reveal about odronextamab?

The ELM-1 clinical trial, led by Dr. Matthew Matasar from Rutgers Cancer Institute, studied odronextamab in 60 people with DLBCL who had previously received CD19 CAR T-cell therapy. About half of the participants had been treated with axi-cel, while the others had received tisa-cel, liso-cel, or other CD19 CAR-T products. 

Odronextamab was given by IV infusion several times during the first four 21-day treatment cycles, followed by maintenance dosing until the cancer worsened or side effects outweighed the benefits. On average, patients received the treatment for 12 weeks. 

Achieving remission with odronextamab for DLBCL

48% of all patients achieved partial or complete remission (overall response). This number decreased to 33% for patients who had relapsed less than 180 days after prior CAR-T. Remission from odronextamab lasted an average of 14.8 months. 

32% of all patients achieved complete remission. The likelihood that these patients stayed in complete remission for two years was 68%. 

Other meaningful insights included that odronextamab’s effects were consistent across high-risk DLBCL types, and the prior brand of CD19 CAR T-cell therapy did not affect patients’ outcomes. 

Did odronextamab help improve immune system function?

Yes. One concern after CAR T-cell therapy is whether patients’ T-cells are still capable of targeting lymphoma. Odronextamab helped increase T-cell numbers in patients, regardless of which CAR T-cell therapy they had before or how recently they received it. This is an encouraging sign that the immune system can still be effectively engaged following CAR-T. 

What were the side effects of odronextamab? 

48% of patients experienced mild to moderate (grade 1-2) cytokine release syndrome, a flu-like reaction that can occur when the immune system is activated.

About 77% of patients needed hospital care (grades ≥3) for side effect management, mostly due to low blood counts. This did not, however, limit the majority of patients’ ability to continue receiving treatment, as only 8% of patients needed to discontinue therapy due to side effects. 

Another important finding was that no cases of ICANS (immune effector cell-associated neurotoxicity syndrome) were reported from odronextamab. ICANS is a brain-related side effect that can cause confusion or, in rare cases, seizures. While it’s more common with CAR T-cell therapy, it has also been seen with some bispecific antibodies in up to 8% of patients. The absence of ICANS with odronextamab is especially noteworthy given this context.  

Learn more about the study’s results in our interview with Dr. Matasar!

Summary

In the ELM-1 clinical trial, people with DLBCL who had previously received CD19 CAR T-cell therapy were treated with a new bispecific antibody called odronextamab for about 12 weeks. Around half of the patients went into remission. Among those who responded, remission lasted an average of 14.8 months. 

Patients who achieved complete remission had a better chance of staying in remission longer. Those who relapsed within six months of prior CAR-T were 15% less likely to respond to odronextamab.

Side effects like low blood counts that required patients to be monitored in the hospital did not stop the majority of individuals from continuing to receive treatment. As well, odronextamab worked well across different high-risk types of DLBCL and had the same effect regardless of the previous CAR-T brand patients received. 

These results show that odronextamab may be a viable treatment option for DLBCL patients if CD19 CAR T-cell therapy didn’t work. 

Review your eligibility to receive odronextamab in the ELM-2 study

To learn how other bispecific antibodies compare after CAR-T in DLBCL, click here.

Source: 

• Efficacy and Safety of Odronextamab Monotherapy in Patients (Pts) with Diffuse Large B-Cell Lymphoma (DLBCL) Progressing after CAR T-Cell Therapy: Primary Analysis from the ELM-1 Study