What is the treatment approach for Richter's transformation of chronic lymphocytic leukemia (CLL) into diffuse large B-cell lymphoma (DLBCL)?

Treatment Approach for Richter's Transformation of CLL into DLBCL

The treatment of Richter's transformation (RT) from CLL to DLBCL should be guided by clonal relationship testing, with R-CHOP as first-line therapy for most patients and allogeneic stem cell transplantation recommended for all patients with clonally-related RT who have an available donor and sufficient fitness. 1

Diagnosis and Initial Evaluation

• Definitive diagnosis requires:

  • Excisional lymph node biopsy (gold standard) or core needle biopsy when excisional biopsy is not feasible 1
  • PET/CT scan to guide biopsy site selection (target lesions with highest FDG uptake) 1
  • Histopathological confirmation
  • Clonality testing to establish relationship between CLL and DLBCL by comparing IGHV sequences 1

• Essential workup includes:

  • Complete blood count with differential
  • Comprehensive metabolic panel
  • LDH and uric acid levels
  • Epstein-Barr virus evaluation (EBV-LMP1 or EBER-ISH) 1

Treatment Algorithm Based on Clonal Status

1. Clonally Unrelated RT (20% of cases)

• Treat as de novo DLBCL 1, 2
• R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy
• Reserve stem cell transplantation for non-responders or relapse after R-CHOP
• Better prognosis (similar to de novo DLBCL) 3

2. Clonally Related RT (80% of cases) or Unknown Clonal Status

• First-line treatment:

  • Clinical trial enrollment (preferred if available) 1
  • R-CHOP if clinical trial not available 1, 2
  • More intensive regimens (R-hyperCVAD, OFAR) have not improved outcomes and cause considerable toxicity 1

• Post-remission therapy:

  • Allogeneic stem cell transplantation (alloSCT) for all patients with available donor and sufficient fitness 1
  • Autologous stem cell transplantation can be considered for patients unsuitable for alloSCT 1

Prognosis and Monitoring

• Clonally related RT-DLBCL has poor prognosis with median survival <1 year with conventional chemoimmunotherapy 4, 5
• Response duration is typically short, necessitating consideration of stem cell transplantation 1
• Predictors of better response to chemoimmunotherapy include elevated platelet counts, higher hemoglobin levels, lower beta-2-microglobulin levels, and lower LDH levels 1

Special Considerations

• RT occurs in 2-15% of CLL patients, with transformation rate of 0.5-1% per year 2, 3
• Risk increases with multiple prior lines of chemoimmunotherapy 1
• RT has been reported after treatment with novel agents like ibrutinib and venetoclax 1
• Transformation to Hodgkin lymphoma variant has better prognosis and should be treated with conventional Hodgkin lymphoma chemotherapy regimens 1

Pitfalls to Avoid

• Do not rely solely on PET scan for diagnosis: While SUVmax ≥10 can suggest RT, tissue biopsy is required for definitive diagnosis 1
• Do not use intensive regimens as first-line: More intensive regimens like R-hyperCVAD or OFAR have not improved outcomes and cause significant toxicity 1
• Do not delay transplant evaluation: Given the short response duration, early evaluation for stem cell transplantation is critical for eligible patients 1
• Do not miss EBV testing: EBV infection has been reported in 16% of RT patients and is associated with poor outcomes 1

By following this algorithm, clinicians can provide the most evidence-based approach to managing this challenging complication of CLL with historically poor outcomes.