At this meeting I presented the long-term efficacy data of the ELM-2 study arm for follicular lymphoma patients which has now been presented with new follow-up data. The ELM-2 study is a multi-arm study of ordronextamab single agent for the treatment of relapsed/refractory lymphoma. One of the arms of the study included only follicular lymphoma patients, relapsed/refractory after at least two prior lines of therapy. The study was initially presented a couple of years ago and published last year in Annals of Oncology, showing high activity in terms of response rates, efficacy in terms of progression free survival and with safety details that are in line with observed with other bispecific antibodies.
This preliminary initial data allowed for the registration of ordronextamab for the treatment of relapsed/refractory patients that had at least two prior lines of therapy in Europe.
The present update shows additional details about the follicular lymphoma arm of the ELM-2 study with longer follow-up. So the ELM-2 study investigated single agent orderonextamab which was used IV until treatment progression or toxicity with an initial step-up dosing that was updated as a three-weeks step-up dosing after the initial two week dosing in the initial design of the study. The primary study endpoint was overall response rate.
Overall, 128 patients were enrolled, showing the features of aggressive disease and high-risk disease, as expected for relapsed/refractory patients. The response rates were, I would say, better than the original reported data with a CR rate of 74%, which is the highest among the complete response rates of other bispecific antibodies in the same follicular lymphoma setting, with an overall response rate of 80.5%.
In terms of efficacy, the median progression free survival was also improved compared with initial reports and was described as 23 months, being longer, 24.5 months in the median duration of PFS for patients who were able to achieve a complete response after giving treatment. The median overall survival was also excellent, being reported at 54.2 months overall, again, with better results with the overall survival was only observed for the patients who achieved a complete response rate.
So in terms of safety no new signal was observed compared with the primary analysis. CNS was confirmed as being the most frequent adverse event which, however, was reported as being grade 1 or 2 and mainly limited to the first cycle of step-up dosing of the treatment. Other safety signals were consistent with the original analysis with a significant number of patients who experienced treatment emergent adverse events, some of which were also associated with treatment discontinuation and in 20 cases the treatment emergent adverse event was also associated with death. However, out of these 20 patients only five treatment adverse events which were leading to death were associated with, correlated somehow, to the treatment, with only one additional case compared to the primary analysis.
Looking at the quality of the events, the most clinically relevant event in this case was that of infection. We have to say that the ELM-2 study enrolled patients during the very hard time of the COVID pandemic and actually 32.8% of patients experienced COVID infection which was, however, severe only in a few of them.
No ICANS were reported in this study, only one grade 2 event was described but the study actually confirmed that ICANS is not an event which is associated with the use of bispecific antibodies.
So, in conclusion, also this long-term follow-up of ordronextamab for the treatment of relapsed/refractory follicular lymphoma patients confirms the very high activity and efficacy of the treatment that is consistent with the prior data even with a longer follow-up. The safety profile was generally manageable.
Overall, all this new data confirms that ordronextamab has a very promising activity and a promising role in the future treatment landscape of follicular lymphoma patients and in other lymphomas. But particularly in follicular lymphoma patients this data strongly supports the rationale for conducting additional studies, mainly in combination regimens. There are actually at least three studies in the OLYMPIA programme which are testing ordronextamab alone or in combination with lenalidomide or chemotherapy with chemo-free options in the relapsed/refractory setting, but, most important, with immunochemotherapy in the newly diagnosed setting, allowing to see that if this trial will be positive, as expected from the initial design, initial hypothesis, ordronextamab will contribute significantly to shaping the treatment landscape of follicular lymphoma patients.
