Advancing Care in CLL Richter Transformation: Adam S. Kittai, MD

When chronic lymphocytic leukemia (CLL) transforms into an aggressive lymphoma, clinicians suddenly face 2 cancers instead of 1. This scenario, known as Richter transformation, remains among the most challenging in hematologic oncology, but new therapies are beginning to shift the outlook.

Adam S. Kittai, MD, director of the CLL Program at Perlmutter Cancer Center; director of the Lymphoma Program at Perlmutter Cancer Center–Long Island; and associate professor at NYU Grossman School of Medicine, explained why the transformation carries such a poor prognosis and where he sees reason for optimism. As with transformation in any cancer, Richter transformation is typically associated with worse outcomes. The difficulty is compounded by the need to treat both the underlying CLL and the resulting diffuse large B-cell lymphoma (DLBCL), Kittai noted.

Still, progress is real. The growing number of CLL therapies has been carried over into the treatment of Richter transformation, and survival appears to be improving. “We’ve made some improvement where patients with Richter transformation do appear to be living longer in the era of modern therapies, but there’s still work to do,” Kittai said.

Among the ongoing efforts he finds most promising is a European trial combining pirtobrutinib with a bispecific antibody.¹ His enthusiasm stems from evidence that bispecific antibodies and chimeric antigen receptor T-cell therapy appear effective in patients who have classically had a poor prognosis. The hope, he explained, is that results seen in chemorefractory DLBCL will translate into better outcomes for patients with Richter transformation.

Because Richter transformation is relatively rare, few clinical trials are designated specifically for it, although Kittai said that situation appears to be improving. In the meantime, investigators can extrapolate heavily from studies in CLL and DLBCL to design novel combination strategies. The goal, he emphasized, is to develop regimens that will “make strong impacts for survival of this terrible disease.”

Kittai’s message is one of cautious optimism: outcomes are moving in the right direction, and the next generation of combination therapies may push them further still.