Advances in Lymphoma
Transcript: Key takeaways from EHA2024
Professor Wojciech Jurczak
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But talking about the conference itself, the conference resembles that there's general change in systemic lymphoma therapy. While chemotherapy is the therapy of the past, chemo immunotherapy is also therapy of the past, and now what we have at the moment is new treatment combinations of immunotherapy, targeted chemotherapy and molecular targeted therapy. And in immunotherapy, there were biospecifics, which were most stunting, as most of the CAR T-cell data we already had, and therefore, on EHA, we had bispecifics for every kind of lymphomas. The most important presented study in a plenary session was a Phase III STARGLO, which is a glofitamab combined with GemOx versus R-GemOx. That's a very interesting study design, where we add bispecifics to chemotherapy.
There's 2:1 randomizations, therefore we had 183 patients treated with glofit-GemOx and only 91 patients treated with R-GemOx, and we're talking about patients failing at least one line of therapy, although the randomization was stratified one versus two or more, failing one versus two or more lines of therapy. That was a very ambitious study where the primary endpoint was an overall survival, a very rare phenomenon. We can clearly say that it's statistically significantly different, allowing for an important prolongation for glofit-GemOx-R. The median progression-free survival was not reached versus nine month on the median follow up of 11 months. Certainly, the progression-free survival and the response rates were similar, similarly in favour of patients treated with glofitamab combination, and this was true for all subgroups analysed. The regimen was very well tolerated with only 7% of neurological adverse events of grade three or greater, according to CTCA, less than 1% of ICAM, and it really was a regimen which could have been employed in elderly population. Talking about low-grade lymphomas, we had an upgrades of epcoritamab data, where Professor Vitolo presented the changed regimen where we edit one additional dose of epcoritamab in the rampant phase and exchange prednisone to dexamethasone as CRS prophylaxis made the regimen entirely outpatient. We literally didn't have any grade three or more CRS, the only grade three and four adverse events were neutropenia, which we haematologists can manage pretty freely. Achieved, we confirmed on the new cohort the satisfactory response rates of 85 plus percent, including 64% of complete regressions. And certainly, as with all studies with bispecifics, the patients achieving MRD negativity were doing better and the median progression-free survival was not met in those population, which is rare. The study was simultaneously published in "Lancet Haematology," the moment the presentation was given on EHA.
Certainly, if we compare the algorithm regimen versus the historical standards of care, the responses were very much different, which was particularly important in complete responses were in separate risk subgroups were in a range of 60 to 80 versus 13 to 28% of complete regressions. Now, we also had some mosunetuzumab data in a heavily re-treated follicular lymphoma. And so, the presentation we had at EHA concentrated on subgroup analysis, it should be of notice that mosunetuzumab as opposed to epcoritamab is given in a time fixed regimen allowing for eight cycles in patient's receiving complete regression and 17 cycles in those with PR. And we analysed different subgroups like those with POD 24 and without, elderly and younger patients, and there was absolutely no difference, both in response rates and in progression-free survival. However, we could demonstrate the difference in patients treated in a third line of therapy versus those treated in a fourth and subsequent lines of therapy, and certainly, the earlier was the better. And there was an important difference in progression-free survival without difference in overall survival. The last interesting analysis of this study was the analysis of immunoglobulin changes over time and occurs that the B-cell recovery was prolonged. It took six months after the discontinuation of mosunetuzumab and the levels of the EGM and EGG recovery was even more prolonged and it took place 12 months after completing the mosunetuzumab therapy. Just to say something about mantle cell lymphoma, we have more and more data saying that the life after BTK resistance, talking about mantle cell lymphoma, we have accumulating evidence that we may successfully treat patients failing the covalent BTK inhibitors, several approved methods like non-covalent BTK inhibitors, talking about pirtobrutinib FDA and DHA approval, but also CAR T cells.
At EHA, Tycel Phillips presented his glofitamab data, so another bispecific monoclonal again use in a traditional schedule, allowing for 90% of response rate, including 86% of complete responses and a reasonable for this group progression-free survival, perhaps even with a plateau on the 40% basis after 24 months. Therefore, I would say that the bispecific results were most important part of EHA and they should most likely become the next standard of care, if not replacing CAR T-cell therapy, allowing for the T-cell engagers to be used in a more numerous population.
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