ASH 2023 | Advancing treatment for patients with Richter’s transformation

So, Richter’s transformation is an aggressive phenomenon. It occurs in patients with CLL who typically transform to a diffuse large B-cell type histology, and has been historically characterized by patients relapsing with this disorder in the relapsed/refractory setting, historically very chemotherapy-resistant and associated with poor survival, aggressive kinetics and challenging genomic environment. And so this phenomenon is feared by CLL patients, rightly, and is a disease that we haven’t made huge progress with over a number of years, partly because of the rarity of the disease, partly because of the challenges in enrolling in clinical trials, and also partly in the fact that no specific agents, novel agents, have been approved in Richter’s transformation, per se, over these last few years. So, we are left with a challenging situation in Richter’s transformation. 

However, there are a number of therapies that are proving to be efficacious that have been studied in relatively small Phase II non-randomized studies, and these include non-covalent BTK inhibitors. We’ve seen data over recent times looking at the non-covalent BTK inhibitor pirtobrutinib, showing activity and overall response rates of over 50% in heavily pretreated patients. There are other non-covalent BTK inhibitors in development, and we await data from them in Richter’s transformation. 

There’s data from bispecific antibodies. We have seen previously a small data series with epcoritamab and glofitamab previously. And at this ASH, we’re going to see some data with mosunetuzumab, again showing response rates in heavily pretreated patients of about 40%, with CR of about 20%. So do take a look at that abstract at ASH. So bispecific antibodies, CD3 and CD20 bispecific antibodies are looking very active. And at this ASH, we’re also going to see the largest series of patients treated with CAR T-cell therapy for Richter’s transformation, again in a heavily pretreated population, demonstrating that certainly there’s a proportion of patients that look to have durable remissions, although I was struck by the treatment-related mortality in this study being around about 10% at 12 months. So clearly, delivering CAR T-cell therapy in relapsed/refractory Richter’s transformation is challenging. So there’s promise, but there’s a lot more to do and so I would encourage people to continue to look to enroll in clinical trials and to continue to develop clinical trials to help patients with Richter’s transformation.