ASH 2025: New Treatments for Richter Transformation

At the 2025 American Society of Hematology (ASH) meeting, researchers shared encouraging results from two studies testing targeted treatment combinations for people with Richter transformation. Richter transformation happens when chronic lymphocytic leukemia (CLL) changes into a faster-growing lymphoma, most often diffuse large B-cell lymphoma (DLBCL). Because Richter transformation can be difficult to treat, new therapies in clinical trials may provide more hope. 

A three-medicine targeted approach for Richter transformation

A phase 2 study tested a combination of pirtobrutinib (Jaypirca, Eli Lilly), venetoclax (Venclexta, AbbVie/Genentech), and obinutuzumab (Gazyva, Genentech). 

The study included 12 people with Richter transformation, most of whom had already received multiple prior treatments. Many had high-risk features, such as del(17p)/TP53 mutations, which are linked to poorer outcomes. 

The study found:

• After treatment, 67% of patients experienced complete or partial remission.
• At 12 months since the start of treatment, 82% of patients were alive.

Of patients who experienced remission, several also had undetectable minimal residual disease (uMRD). This means sensitive testing found little to no cancer cells in a sample. This can be a sign of deeper lymphoma control, potentially helping patients maintain remission for a longer period of time. 

Some people whose condition was controlled by the treatment were able to proceed to stem cell transplant. Others continued treatment with the pirtobrutinib, venetoclax, and obinutuzumab combination to keep the cancer under control. 

These findings are important because Richter transformation is often treated with intensive chemotherapy, which can be hard to tolerate and may not work well. This study suggests a chemotherapy-free combination may control the cancer for some patients, even those who have already tried multiple treatments. 

Check Your Eligibility to Join This Study

Read this abstract: Pirtobrutinib, venetoclax, and obinutuzumab for patients with richter transformation: A phase 2 trial

Combining a checkpoint inhibitor with a BTK inhibitor

A German study shared extended follow-up from the RT1 trial, which tested an immune checkpoint inhibitor called tislelizumab (Tevimbra, BeOne) with the BTK inhibitor zanubrutinib (Brukinsa, BeOne).  

This trial included 48 people with Richter transformation, some of whom had received prior treatment. The study found:

• The percentage of patients who experienced complete or partial remission was  58.3%.
• The response to treatment lasted for a median of 17.1 months.
• More than 60% of patients were alive at 2 years.
• Some patients’ responses to treatment lasted for more than 3 years. 

The most common side effects were infections, digestive symptoms, and blood count changes. Knowing what to expect from this treatment combination may help you better weigh treatment options with your care team. 

Why did the treatment work better for some patients compared to others? 

The researchers studied samples of the patients’ cancer cells to understand why the treatment worked better for some patients than others. They found:

• Certain genetic changes of cancer cells, such as del(17p)/TP53 mutations or complex chromosome changes, were linked to a shorter time in remission.
• Patients who had the gene TRAF1 experienced longer-lasting remissions. 

This type of research may help doctors better match treatments to the patients most likely to benefit in the future. 

Read this abstract: Correlates of response to combined checkpoint and BTK inhibition for treatment of richter transformation: Extended follow-up from the prospective RT1 trial

What this means for people with Richter transformation

Together, these studies show that targeted and immune-based treatments can lead to promising outcomes for people with Richter transformation. While these approaches are still being studied and are not right for everyone, they represent progress in a space where options have been limited.

If you have Richter transformation, these results may be worth discussing with your specialist, especially when considering clinical trials or next treatment steps. 

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