ICML 2025 | Promising advances being made in Richter’s transformation: combination approaches & immune therapies

There’s a number of new therapies being explored in Richter’s and I think several of them are promising. It’s encouraging that we’re starting to see chemotherapy-free regimens being developed for Richter’s, particularly because CLL patients tend to be older and have comorbidities and chemotherapy can be challenging in that population. So we see progress on the front of BTK inhibitors like pirtobrutinib, a non-covalent inhibitor where there’s good single-agent activity in terms of inducing response, although the durability of those responses are not that long. And so I think some of the combination approaches, for example, combining BTK inhibitors with immune-based therapies like PD-1 antibodies also look promising. We’ve seen a recent publication on tislelizumab with zanubrutinib that is now being taken into a Phase III setting. We’ve seen also CAR T-cell data in Richter’s starting to evolve. And then in particular, one area that I would like to note is bispecific antibodies. We saw some initial data with glofitamab as a monotherapy at the ICML meeting a couple of years ago, and that looked promising with about half the patients achieving CR. We recently opened at Dana-Farber a multicenter study looking at glofitamab in Richter’s transformation, exploring both monotherapy and combinations of glofitamab with atezolizumab, the PD-L1 antibody, pirtobrutinib, the BTK inhibitor, as well as polatuzumab, the CD79b ADC. So a lot of interest in Richter’s right now. It’s a real area where we can make progress for CLL, and I’m optimistic about it.

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