EHA 2021 | BRUIN: pirtobrutinib shows efficacy for Richter’s transformation

Hi, everybody. This is Anthony Mato from Memorial Sloan Kettering Cancer Center, presenting some interesting data to you from the EHA conference, specifically on the BRUIN Phase I/II trial of pirtobrutinib, and focusing on a patient population with Richter’s transformation.

I think everybody knows Richter’s transformation is one of the most dreaded consequences of CLL, where the indolent disease can become a very aggressive, large B-cell lymphoma. No standard of care. Most of the prior therapies have been extrapolated from therapies for de novo diffuse large B-cell lymphoma with disappointing results.

The data that I’m presenting are for a group of patients treated on the Phase I/II BRUIN trial with Richter’s transformation, who were treated with LOXO-305 or pirtobrutinib. We had presented previously the data for the CLL cohort at the most recent ASH meeting. Those data will be updated by my colleague, Dr Lindsay Roeker. And Richter’s transformation now there’ve been 17 patients who’ve been enrolled on the trial.

So, a reasonable number, heavily pretreated with a median number of prior therapies, including their CLL therapies of six. And so quite heavily pretreated patient population. They’ve had at least two prior therapies for Richter’s transformation. So, a group of patients who truly have no standard of care, high exposure to targeted therapies like BTK inhibitors, chemoimmunotherapy, BCL-2 inhibitors, and a very high-risk genetic patient population.

The major, major take home from this small subset of patients is that pirtobrutinib does appear to be quite active in this particular group of patients which we are reporting on 15 evaluable patients an overall response rate of 67%, 13% CRs, 53% PR. So, actually some patients in complete remission. I can not only report the numbers but speak from personal experience. Several of these are my patients and we did see a high response rate and actually the responses do appear to be quite durable. There will be a swimmer’s plot presented where you can see the patient furthest along in remission is now approximately 14 months, and that’s my patient.

So, relatively short follow-up, but promising results in a small subset of patients provide some hope for patients with Richter’s transformation. Of course, any other, any drug that’s being presented we also have to think about the safety profile. We had seen data from over 300 patients presented at the ASH meeting on pirtobrutinib. Specifically in terms of safety, we saw a less than 2% discontinuation rate for AEs, less than 1% A-fib or A-flutter, very low rate of bleeding. So, the typical BTK-associated toxicities weren’t seen, and in this small group of patients with Richter’s transformation, we saw a similar safety profile. So, well tolerated, active, promising, and now we’re hoping to treat a larger number of patients with Richter’s and to have longer-term follow-up to really get a better sense of the durability of responses.