Advances in Lymphoma
Transcript: Molecularly targeted therapies
Professor Wojciech Jurczak
All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
The other thing I've noticed was the molecular target of therapies and namely we had two presentations. Again, the mantle cell lymphoma, Professor Wang from MD Anderson presented ECHO trial data, a randomised study with 598 patients on board randomised in the first line between bendamustine rituximab and bendamustine rituximab plus acalabrutinib both with maintenance. It may change the standard of current mantle cell lymphoma as the arm with acalabrutinib had a statistically important increase of complete regressions, six to six versus 53% transforming to medium progression to statistic important difference in progression-free survival and overall survival. However, having said so, it was difficult to demonstrate overall survival difference as the study allowed crossover and six to nine patients who received BTK as subsequent treatment for failures. Nevertheless, even with this, we had an important difference if we censor the data for COVID-19 deaths. It should be noticed that if we are treating the lymphoma patients with a lower dynamics, we should possibly encourage them to get vaccinated before the therapy starts.
The adverse events were predictable. There were non-adverse events unexpected in this combination and the incidences of atrial fibrillation of Grade 3 or more was less than 4%, which was more or less what we would've dissipated than this age group. Acalabrutinib didn't cause a more important hypertension or bleeding as opposed to zanubrutinib, so we can say that it could have been the new standard of care, if not the data from the CAR T-cells where in his last paper, Professor Wang elegantly proved that the results in patients whoever get bendamustine are worse.
Another study presented in mantle cell lymphoma patients were SYMPATICO data answer the patients with TP53 mutations. I've noticed that in mantle cell lymphoma, we are talking about mutations and not deletions. Therefore, they could be detected not by the FISH analysis but by more sophisticated methods like NGS or others. Now, we were able to detect 15 to 20% of mutations in mantle cell lymphoma patients more on relapsing refractory. However, we collected data from both untreated patients, 29 of them, and relapsing refractory 45. The patients with relapsing refractory were a part of a randomised study and the treatment regimen here was a combination of BCL2 inhibitor and BTK inhibitor, namely venetoclax and ibrutinib. Such combination gave an excellent 55 to 58% complete regression rate, 88 to 90% of overall response rate. And overall survival was very much different and in a randomised portion, we could clearly see the curve separated between the patients treated with ibrutinib-venetoclax and ibrutinib only.
The medium overall survival in ibrutinib-venetoclax patients was 35 months versus 15 months, and those treated with BTK inhibitor alone. Therefore, it backs up the idea that we should go for an individualised therapy or risk-guided therapy in all mantle cell lymphoma patients and the patients with TP53 mutations, even if treatment naive should not be treated by chemo-immunotherapy.
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