ASH 2022 | Phase II trial of acalabrutinib, lenalidomide and rituximab in patients with MCL

I’m very pleased to be here today at the ASH 2022, where we can be conferencing in-person and discuss our findings and meet up with our colleagues. So we are presenting the abstract, which is abstract 73. It is on a Phase II study with a triple combination including the BTK inhibitor acalabrutinib, lenalidomide, and rituximab as a triplet initial therapy option for patients with mantle cell lymphoma. This study is based on our previous study with a doublet, which is the combination of lenalidomide and rituximab. It’s built on the backbone of the [inaudible] study where patients have an induction phase and also a maintenance phase. During induction, the acalabrutinib was given 100 milligrams twice a day continuously, and lenalidomide was titrated up to 20 milligrams of three weeks on one week off, and also rituximab, which is given weekly for the first cycle and subsequently every other cycle.

The induction goes for 12 cycles. For anybody who has a response or even stable disease, they can proceed to the maintenance part, which repeats the same strategy with a lower dose of lenalidomide. We also devised a molecular PCR analysis of… Actually it’s a molecular minimal residual disease analysis for both induction and maintenance, such that for patients who can achieve MRD negative complete remission, we would have the option of having them de-escalate their treatment intensities, such that they can discontinue the oral acalabrutinib and lenalidomide.

They do have the option to re-escalate coming back onto this triple regimen, if you know there’s disease progression afterwards. And we enrolled 24 patients onto the study who require treatment and they have pretty much typical characteristics of mantle cell lymphoma, they’re extensive stage disease, stage four, they have bone marrow involvement and they have a stratification of their MIPI score to be expected. Overall, I want to say that we’re very pleased to report that this triple combination regimen is quite well-tolerated with expected treatment-related side effects. During the induction, we noticed asymptomatic neutropenia, anemia, and thrombocytopenia, but we have not seen febrile neutropenia, which is good as far as the safety is concerned, and we have seen routine infections that can be managed in the outpatient setting.

We do observe a wave of COVID-19 infection that’s following the Omicron variant, and however, our patients generally would recover with supportive care. So that was very good. From a non-heme toxicity standpoint, we’ve seen a rash and some fatigue initially during induction, and some GI side effects during maintenance, as well as some fever related to the COVID-19 infections.

As far as the response goes, the overall response rate was 100%, based on the Lugano criteria. We’ve seen 83% of CR rate, also based on Lugano criteria. With our real-time MRD monitoring, we’ve seen gradual, I would say, deepening of the molecular response. 50% of patients achieve MRD negative CR after six cycles of treatment. By the time that they get to 12 cycles, it’s over 67% and over 80% when they complete two years, 24 cycles of treatment. And we have about nine patients who are currently in the de-escalation phase where they only receive rituximab maintenance.

So overall, I think we’re quite pleased, obviously, with the outcome of this triplet combination. I do believe that it requires longer follow-ups and hopefully also warrants a larger study and perhaps in comparison with other combinations, either traditional chemotherapy-free or with chemoimmunotherapy.