The study that we’re presenting here addresses the unmet need of patients with diffuse large B-cell lymphoma that has progressed after CAR T-cell therapy. We know that CAR T remains a very important treatment for patients with relapsed or refractory large cell lymphoma but, despite this, cure is uncommon with only approximately 30% of patients expected to be cured by treatment with CAR T. Patients who are failed by CAR T-cell therapy represent a significant unmet need and there is no clear standard of care for how best to treat such patients.
Our data here from the ELM-1 study represents the largest and clearest prospective data set for the use of bispecific antibody therapy to evaluate the hypothesis that such treatment could be effective and safe in patients with large cell lymphoma progressing after CAR T-cell therapy.
What was the study design?
The study design here is drawn from a cohort within the ELM-1 study of odronextamab, a CD20 by CD3 bispecific antibody as monotherapy in patients with multiply relapsed or refractory large cell lymphoma. Treatment with odronextamab was as per its standard treatment with step-up dosing and the study was modified during the conduct of the study to instigate a more gradual step-up dosing to further mitigate the risks of cytokine release syndrome. Treatment was administered as per standard with weekly and then every two weeks up to cycle 9. Patients who achieved a complete response at cycle 9 could be continued at a q4 week dosing schedule until progression or intolerance.
What were the results of this study?
I would say the results here are encouraging. We found that in this heavily pre-treated patient population with this treatment being the median fourth line of therapy in patients who had already been failed by CAR T as the enrolment criterion for this cohort, we saw that odronextamab monotherapy was active with a best overall response rate of 48% and a complete response rate of 32%. Further, we saw the patients who achieved a CR were likely to sustain that CR in ongoing follow-up.
Responses were not just common but also [??] with a median duration of response of 14.8 months. For those patients that achieved a complete response the median duration of complete response has not yet been reached at last data cut.
We saw the treatment was safe as well with a low rate of grade 5 adverse events of only 3%. Serious adverse events were common but largely those which are expected from [??] therapy. Cytokine release syndrome was seen in approximately half of patients but was almost exclusively limited to grade 1 or grade 2 and during step-up administration.
We did see that there was a relationship between time from CAR T-cell therapy and likely effectiveness of odronextamab therapy with patients who had progressed within 90 days of treatment with CAR T-cell therapy less likely to respond to odronextamab with only 20% of such patients responding to odronextamab. Whereas for patients who had relapsed more than six months after CAR T-cell therapy enjoying a very high overall response rate of over 80%.
What do you think is the clinical significance of these results?
The clinical impact here is that it is the first and clearest signal that for patients who have been failed by CAR T-cell therapy, relapsing subsequently, bispecific antibodies do represent a safe and effective strategy for treating such high risk patients. There’s obviously work ongoing with odronextamab in combination with other bispecific antibodies as well, but the study data [??] very clearly points the direction that bispecific antibodies are a relevant and encouraging strategy for these difficult to treat patients.
