ASCO 2024 | A network meta-analysis comparing the efficacy of covalent BTK inhibitors in R/R CLL

At the ASCO meeting, we presented our data using a network meta analysis comparing the efficacy of covalent BTK inhibitors in relapsed CLL. As we know, we have three drugs: ibrutinib acalabrutinib and zanubrutinib. Acala versus ibrutinib and zanu versus ibrutinib have been compared in head to head clinical trials. We don’t have data on the comparison of acalabrutinib versus zanubrutinib. So there are indirect ways of making those comparisons. One example is MAIC or matching adjusted indirect comparison.

In this analysis, we used a network meta analysis, which is a technique that you can compare different interventions and combine direct and indirect comparisons when you have more than three interventions. So here we use the data from ALPINE trial, from ASCEND and from ELEVATE-RR. And what this study showed, we looked at the overall response and CR rates. In terms of overall response, zanubrutinib was superior to ibrutinib for overall response, and that was a statistically significant difference, in terms of CR was not statistically significant. In terms of zanu versus acala for overall response and complete response, we did not detect a statistical significant difference, although numerically the numbers were in favor of zanubrutinib

For progression free survival, we did two types of analysis, adjusted and unadjusted for COVID-19 related deaths. When we looked at the high risk population defined by each study and after adjustment for COVID-19 related deaths, the zanubrutinib treatment was superior to ibrutinib, to acalabrutinib and to chemoimmunotherapy, and that efficacy advantage was persistent regardless of adjusting or not adjusting for COVID-19.

When we limited our analysis to patients with del17p, again, zanubrutinib was superior to ibrutinib, acala and chemo in the adjusted model. But in the unadjusted model, there was no difference in terms of efficacy from the PFS standpoint in del17p between zanubrutinib and acalabrutinib. But zanu was superior to ibrutinib and chemoimmunotherapy. And lastly, when we looked at overall survival, despite some numerical trend, there was no statistically different OS between the treatments.

So overall, we would like to remind ourselves that the first and gold standard of evidence would be head to head randomized trials. In the absence of direct data, we look at analysis like this to inform our investigators, clinicians, and hopefully patients in treating patients with CLL.