I presented at the ASCO meeting and the EHA meeting the results from the MOLTO study. This is a study in patients with diffuse large B-cell lymphoma type, treatment naïve Richter’s transformation. In the study patients had to have ECOG performance status lower than 3. These patients had to be previously untreated for Richter while they could have received a previous treatment for chronic lymphocytic leukaemia. Treatment consisted of three drugs, one was an oral drug, venetoclax, and this was started from day 15 of cycle 1 and then continued until the end of treatment, that consisted overall of 21 days each cycle. The other two drugs were given intravenously and were obinutuzumab given at day 1 until cycle 8 and then atezolizumab given at day 1 until cycle 18.
The rationale of this study is the combination of a checkpoint inhibitor, atezolizumab, an anti-PD-L1, with a BCL2 inhibitor, venetoclax, that is able to overcome the negative effects of a TP53 aberration while PD-L1 is highly expressed in patients with Richter. So the combination of these two agents with a second generation monoclonal antibody against CD20 could be an effective strategy in patients with Richter.
The primary endpoint of this study was an overall response rate greater than 67% and this was based on the static results with R-CHOP. Then we had some other secondary endpoints of quality of response and safety and survival, of course. The study reached the primary endpoint of overall response rate but, even more important, responses were really durable. We saw a median duration of response of 26.3 months, that is really a long time considering this disease has a really poor prognosis and the median overall survival is usually less than one year. None of the clinical and disease and biological characteristics that we evaluated affected the response rate or complete remission, while we saw a worse progression free survival in patients with a performance status of 2 versus 0 or 1. In this case this ECOG performance status affected also overall survival.
What are the next steps for this trial?
Enrolment has been closed in October 2022. Our results showed an efficacy of checkpoint inhibitor in this kind of disease and of venetoclax in this kind of disease. But our results confirm these similar results shown also from other groups so we hope that with an increasing number of studies these drugs could be approved or could be, anyway, an option, a valid option, for these patients.
