R-CHOP Plus Ibrutinib Leads to CR in Richter Syndrome

A new case report is bolstering the argument for the use of Bruton tyrosine kinase (BTK) inhibitors in combination with chemoimmunotherapy (CIT) in patients with Richter syndrome (RS), a rare and aggressive complication of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The report was published in Leukemia Research Reports.¹

The authors noted that BTK inhibitors are commonly used for patients with relapsed or refractory CLL or SLL.

“While BTK [inhibitors] have changed the treatment algorithm for CLL/SLL, their role in RS is not well established,” they explained.

They said it is critically important to optimize front-line treatment of RS, particularly as newer therapies have been developed for CLL and SLL. In the new case report, they explained what happened when they successfully treated a patient with diffuse large B-cell lymphoma–type RS using a BTK inhibitor alongside CIT.

The case involved a 64-year-old man who appeared in the clinic with decreased appetite, shortness of breath, abdominal distention, and scrotal pain, which the patient said he had been experiencing for approximately 6 weeks. He had a history of ventricular tachycardia and type 2 diabetes, they said.

Abdominal ultrasound and CT both indicated he had splenomegaly, as well as bilateral pleural effusions and bulky lymphadenopathy near the pancreatic head and in the porta hepatitis. The patient underwent thoracentesis cytology, flow cytometry, and lymph node biopsy, which eventually resulted in a diagnosis of Richter’s transformation of SLL with TP53 deletion.

The patient was started on the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin [Oncovin], prednisone) CIT regimen, along with ibrutinib (Imbruvica; iR-CHOP) at 560 mg per day. Ibrutinib was added during the second cycle of R-CHOP to mitigate the risk of tumor lysis syndrome, the authors said.

Restaging PET-CT scans at cycles 3 and 6 demonstrated improvement, eventually reaching the criteria for complete remission (CR) and a Deauville score of 2. After completing iR-CHOP, the patient was continued on maintenance ibrutinib. He then received an allogeneic hematopoietic stem cell transplant (allo-HCT) from a matched unrelated donor as a consolidative strategy, and ibrutinib was stopped, as well as conditioning and graft-vs-host prophylaxis. The transplant itself was complicated by neutropenic fever, grade 3 mucositis, and acute internal jugular venous thrombosis, the investigators said.

The patient was discharged at day +18 with complete neutrophil engraftment. At day +30, a bone marrow biopsy revealed morphologically normal bone marrow and no evidence of CLL/SLL, the authors said. Subsequent restaging studies confirmed CR.

“At the time of writing, patient remains 3+ years in CR after completing combination treatment with iR-CHOP treatment and an allo-HCT,” the authors said. “He also maintains an excellent quality of life and works full time.”

They noted that TP53 deletion has been linked with a poor prognosis in CLL/SLL and is a predictor of poor response to chemotherapy.²

“In view of our patient’s adverse prognostic factors at the time of initial presentation, we initiated treatment with R-CHOP CIT, which currently remains the standard of care in patients with newly diagnosed RS and combined it with a novel agent (BTK inhibitor),” they said. “Treatment with this novel combination therapy led to a rapid response and our patient was able to proceed with a consolidative allo-HCT in a state of CR.”

The investigators said they reviewed existing literature, which suggests growing support for the addition of BTK inhibitors in the front-line management of RS. They noted that additional prospective trials are ongoing, the results of which, they said, will hopefully “pave the way for a new treatment standard in the management of RS.”

References

1. Meier T, Huynh G, Ayala E, Tun HW, Iqbal M. Bruton tyrosine kinase inhibitors in combination with chemoimmunotherapy is an effective treatment for patients with Richter’s syndrome. Leuk Res Rep. 2026;25:100564. doi:10.1016/j.lrr.2026.100564.
2. Döhner H, Fischer K, Bentz M, et al. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood. 1995;85(6):1580-1589.