Richter’s transformation

Refers to the histologic transformation of CLL to an aggressive lymphoma.

More than 90% of patients with Richter transformation present with diffuse large B-cell lymphoma.

Up to 10% of patients with CLL and small cell lymphocytic lymphoma will undergo transformation to large cell lymphoma, the Richter’s syndrome.

The large majority of patients with RT have histology similar to diffuse large B cell lymphoma.

Is independent of the duration of CLL , the disease stage or type of therapy or response to treatment but is more common during the later stages of the disease.

Associated with rapid enlargement of lymphadenopathy, systemic symptoms, the development of extranodal disease and an increase in the LDH level.

Patients present with B symptoms with fever, chills, night sweats, and unintentional weight loss, and elevated LDH levels.

Associated with poor prognosis in those that develop the disease.

Clinical outcomes of RT patients are markedly inferior to those with CLL, or denovo DLBCL, highlighting that RT is a distinct entity.

In patients treated with chemotherapy or chemo immunotherapy for CLL transition to RT ranges from 1-10% after a median followup of  3-13 years.

Genetic features include the loss of genes, regulating DNA repair damage – TP 53 and cell cycle, CDKN2A/B, over expression of MYC, activation of NOTCH signaling, and MAPK pathways and, and gnomic instability.

Such genetic lesions characteristic of RT can proceed the clinical diagnosis by 6 to 19 years.

Patients with RT present with profound B symptoms, rapidly enlarging lymph nodes, progressive cytopenia, hypercalcemia, and/or extranodal disease.

PET imaging can guide tissue biopsy material and is a useful for a diagnosis and following the disease.

PET SUV 5 or greater is a useful cut off for acceptability and specificity for the diagnosis.

The incidence of RT in patients treated with venetoclax is higher than those patients treated with Ibrutinib.

Median overall survival 5-8 months.

Sould be treated with combination cytoreductive therapy plus rituximab.

Rituximab based, anthracine containing chemoimmunotherapy is the standard initial treatment-R-CHOP.

The response rate for RT with these agents is less than half at 37–46% and the short duration of median progression free survival is only 3 to 10 months.

The addition of Venetoclx to R-CHOP increases the response rate to double at 62%, including 50% complete responses.

For patients who achieve complete remission consolidation with allogeneic hematopoietic stem cell transplant, can achieve durable disease control in selected patients.

Patients with relapsed or refractory RT have poor survival and limited treatment options.

Agents considered in these patients include BTK inhibitors, immunecheckpoint inhibitors, bIspecific antibodies and CAR-T therapy.

Pembrolizumab active in Richter’s tranformation but not in CLL.

PET scans have a high sensitivity and specificity for detecting RT.