Allison M. Winter, MD, on Richter Transformation: New Data on a CAR T-Cell Treatment

Richter's Transformation is a feared complication of patients with CLL. It happens in a minority up to 1% of patients, but it's associated with poor outcomes with a historical median overall survival anywhere from three to 12 months. We looked at the use of lysis cell as a commercial infusion just for patients with Richter's Transformation using data from the CIBMTR. The data included 30 patients who received a single infusion of lysis cell commercially, who had at least six months of follow-up until the data cut off of February 2023. We looked at outcome measurements, as well as previous lines of therapy and safety data. It's important to note that many of these patients were high risk. Some of the features that made them high risk included things like 77% of patients had prior therapy for their CLL, prior to the Richter Transformation event. 90% of these were large B-cell lymphoma histologies. All patients received therapy, obviously for their Richter Transformation before they received their infusion of lysis cell. It's important to note that 83% were refractory to their last line of therapy prior to their lysis cell infusion. Many of these patients had prior therapies with novel agents including BTK inhibitors, BCL-II inhibitors, and even chemoimmunotherapy. Some patients were even dual class exposed to both BCL-II inhibitors and BTKI inhibitors. Two patients even had active CNS disease at the time of the lysis cell infusion. For the patients who had the one-time infusion of lysis cell, 76% was the overall response rate with 66% CR's. And this was a pretty quick response. Most patients had a response by 1.1 months. Of those patients who did have a response and had duration of response data available, 77% had a 12-month duration of response. When we look at the outcomes in more depth, we see that the median progression free survival was not reached. At six months, it was estimated at 65%. And at 12 months, 54%. All patients had survival data available. The six-month overall survival was 79%. And at 12 months estimated at 67%. It's important to look at safety in these CAR T-cell products, especially in this real world setting. 70% of patients had cytokine release syndrome, but thankfully grade three or higher was low in just 7% of patients. 47% did experience ICANNs, but again, the grade three and higher was lower at 27%. So this is, again, a multi-center real world data set from the CIBMTR, looking at lysis cell infusion commercially. Showing high response rates in long, durable responses in this high risk, difficult to treat Richter's Transformation population. We recognize that larger cohorts and longer follow-up is required to really characterize lysis cell in the future in this population.