EHA 2022 | ZUMA-7 subgroup analysis: axi-cel vs SOC in elderly patients with R/R LBCL

So, what I presented in this EHA 2022 meeting is a pre-planned subgroup analysis of the ZUMA-7 prospective clinical trial that basically compares in patients that, in principle, are candidates for autologous stem cell transplantation that have a primary refractory or earlier relapsed diffuse large B-cell lymphoma. Axi-cel versus the standard of care, which is salvage conventional chemotherapy and consolidation with auto transplant. So, I presented the subgroup analysis, looking at the elderly population of patients. So, patients aged 65 years of age or older than that, and they represent around 109 patients of the global population of patients included in ZUMA-7. So, basically, the clinical findings in this population of patients resemble quite a lot the findings that we had in the ITT population. So, more than 90% of these patients that were randomized to the axi-cel arm, they were able to end up being treated with axi, while only 34% of the patients that were randomized to the standard of care arm, and receiving autologous stem cell transplantation.

The major reason for that, is that they did not achieve a complete remission, or a partial remission with the standard of care. Event-free survival was the primary endpoint of the trial and the event-free survival for the selected population of patients was significantly better with axicabtagene than with the standard of care in a similar way to what we have seen with the intention to treat population. The overall response rate was also significantly higher in the axi-cel treated group versus the standard of care treated group in the same way that complete remission was also higher in this group of patients. The median follow-up, I haven’t said that is 24 months, which is not so bad for the type of patients that we are analyzing here, because most of the events are being seen in the first two years after receiving therapy.

So, there was also pre-planned analysis regarding overall survival and the overall survival curves for the axi-cel treated patients were also better than for the standard of care treated patients taking into consideration that more than 50% of the patients in the standard of care treated group, when they failed, or they progressed to autologous stem cell transplantation, they received some sort of cellular therapy. So, maybe axi-cel in third line, or maybe another anti-CD19 autologous CAR-T cell construct. Another important thing that I presented were the patient reported outcomes that constitute a very important endpoint for all these prospective clinical trials.

That’s also important because the elderly population of patients, they usually tolerate treatments less well than the younger population of patients. In the same way that we saw in the intention to treat population of patients, the patient reported outcomes. So, in terms of all the validated questionnaires of the EORTC, which are probably one of the most used ones, they benefit axi in front of the standard of care, both on day plus 100, and then on day plus 150. The safety profile that, of course, it’s also an important issue of concern in all patients, but also in the elderly population of patients was quite similar to what we know from other patients being treated with axi-cel inside or outside perspective clinical trials, maybe the incidence of grade three or plus CRS. The incidence of grade three or plus neurological events was a little bit higher than the intention to treat population, but the rates were really quite acceptable and everybody thinks that axi is a safe procedure in this population of patients. In fact, there were not specific treatment-related deaths to axi-cel in this group of patients. So, basically the conclusion is that, of course, for these elderly population of patients where we have a big unmet medical need and that have really bad prognosis because they are primary refractory, or they relapse early after first line treatment strategy, treatment with axi-cel could be a perfectly valid treatment option.