Also known as Richter’s Transformation, Richter syndrome is a rare and aggressive complication of chronic lymphocytic leukemia (CLL). When someone develops Richter syndrome, their CLL can transform into another rare form of non-Hodgkin’s lymphoma, most often diffuse large B-cell lymphoma (DLBCL). Unfortunately, this can be hard-to-treat and comes with a poor prognosis. Most individuals live only 8-12 months following diagnosis. Identifying and testing novel treatment options is crucial to improving the lives of those affected.
According to OncLive, data presented at the 17th Annual International Conference on Malignant Lymphoma suggests that Columvi (glofitamab) could show promise in treating Richter syndrome, following Gazyva (obinutuzumab) pretreatment. The data comes from the dose-escalation portion of a Phase 1 study, in which 11 participants with heavily pretreated Richter syndrome enrolled.
Unpacking the Trial Data
During the study, participants received glofitamab on either a fixed-dose (ranging from 0.6mg to 25mg) or step-up dosing (either 16mg or 30mg) schedule. The researchers aimed to understand whether the drug was safe and well-tolerated, its pharmacokinetic profile, and what the maximum tolerated dose was for further studies.
The median follow-up period was 40.8 months. At the time of follow-up, the research team found that:
- Glofitamab contributed to a 63.6% overall response rate. Of this, 45.5% of individuals saw a complete response and 18.2% saw a partial response. Learn more about these endpoints.
- This treatment led to a sustained and durable response, with many responses remaining for over 33 months—even though treatment time was typically less than 6 months.
- Most trial participants saw their tumors shrink by half or more than half, with some individuals seeing tumor reduction ranging from 90-100%.
- Despite a majority of trial participants being refractory to prior treatments (i.e. not responding well to treatments), many individuals responded well to glofitamab.
- While the researchers note that the safety profile is manageable, all trial participants experienced some sort of adverse reactions; 54.5% of participants experienced a serious treatment-related adverse reaction.
- The most common side effects included fatigue, fever, cytokine release syndrome, headache, rashes, and thrombocytopenia (low platelet counts).
Ultimately, the study found that step-up dosing with glofitamab could offer a promising new way to manage Richter syndrome.
About Richter Syndrome
Richter syndrome only occurs in 2-10% of individuals diagnosed with CLL. Certain genetic characteristics, specific genetic mutations, or CLL cell biological characteristics all increase the risk of developing this complication. Symptoms associated with this syndrome may include:
- Lymphadenopathy (a sudden and dramatic swelling of the lymph nodes)
- Fatigue
- Night sweats
- Unintentional weight loss
- Fever
- Dizziness
- Shortness of breath
- Excessive bruising and bleeding
- Heart palpitations
