What is Richter’s Syndrome and How is it Treated?

Published: March 24, 2021

Medically Reviewed By: Jennifer R. Brown, MD, PhD

Richter’s syndrome involves the rapid transformation of chronic lymphocytic leukemia (CLL) into a significantly more aggressive form of lymphoma, usually diffuse large B-cell lymphoma (DLBCL), but occasionally Hodgkin lymphoma (HL). It arises in 2-10% of all patients with CLL and can occur at any time in the course of the disease.

The goal of treatment for Richter’s syndrome is to generate remissions that make patients eligible for a stem cell transplant or other consolidation therapy, which holds the potential for long-term survival. Dana-Farber investigators are currently leading clinical trials of treatments that show promise of improving outcomes.

What are the symptoms for Richter’s syndrome?

The most common symptom of Richter’s syndrome is the sudden appearance of a large lymph node in the neck, abdomen, underarm area, or groin. Other symptoms can include:

• drenching night sweats
• worsening fevers or chills
• unexplained weight loss

While some of these symptoms are associated with CLL itself, a sudden or dramatic worsening of them can be a signal of the development of Richter’s syndrome.

How is Richter’s syndrome diagnosed?

Patients with these symptoms should be evaluated by a physician, as the same symptoms can be produced by infection or other cause. If Richter’s syndrome is suspected, the patient may undergo a PET scan, which can detect the disease and help doctors determine which lymph node should be biopsied for examination by a pathologist. The pathology exam can determine whether CLL has become more aggressive or has transformed into Richter’s syndrome.

What causes Richter’s syndrome?

Doctors and scientists don’t know what causes CLL to transform into Richter’s syndrome. But certain factors can increase patients’ risk, such as:

• previous treatment for CLL
• loss of a section of chromosome 17p in tumor cells
• an abnormal Notch protein in tumor cells

How is Richter’s syndrome treated?

The standard first-line treatment is a chemotherapy regimen known as R-CHOP (for the drugs rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone). In recent years, Dana-Farber investigators have tested a similar chemotherapy regimen in combination with the targeted drug venetoclax. Patients with Richter’s syndrome marked by an abnormal p53 protein tend to become rapidly resistant to chemotherapy agents; it’s hoped that the addition of venetoclax will restore the cancer’s susceptibility to these drugs.

In one clinical trial, Dana-Farber researchers found that a combination of the EPOCH-R regimen (which includes etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and venetoclax produced a promising rate of complete remissions, albeit with a significant level of side effects. The investigators are planning a follow-up trial of R-CHOP and venetoclax.

While these approaches are often successful in producing remissions, the remissions tend not to be long-lasting. The goal of treatment is to generate remissions that make patients eligible for a stem cell transplant — the only current therapy associated with long-term survival. Alternatives under investigation include maintenance therapy, such as the above-mentioned clinical trial involving venetoclax.

Dana-Farber investigators are currently leading clinical trials of two regimens that have potential to produce more durable remissions:

• A study of copanlisib (a drug targeting the PI3K protein) in combination with nivolumab (an immunotherapy agent)
• A study of the PI3K inhibitor duvelisib and venetoclax

Both are based on research suggesting that the drugs used in combination reinforce each other.

Some patients who don’t have a remission of their disease with standard chemotherapy regimens may be treated with a CAR T-cell therapy, which uses genetically modified versions of patients’ own immune system cells to generate a potent attack on lymphoma cells.

To better understand the biology behind Richter’s, Dana-Farber scientists led by Catherine Wu, MD, have applied for a grant for a basic research study into the syndrome. Insights from the study may help scientists develop new approaches to treatment.

‍