What is the recommended treatment for follicular lymphoma that transforms to Diffuse Large B-Cell Lymphoma (DLBCL)?

Treatment of Follicular Lymphoma Transformed to DLBCL

For follicular lymphoma that transforms to Diffuse Large B-Cell Lymphoma (DLBCL), anthracycline-based chemoimmunotherapy followed by consideration of consolidation with high-dose therapy and autologous stem cell transplantation (HDT/ASCR) is the recommended treatment approach for patients with minimal or no prior chemotherapy exposure.

Initial Treatment Approach

For patients with minimal or no prior chemotherapy:

1. First-line treatment:

   • Anthracycline-based chemoimmunotherapy (R-CHOP being most common) ± involved site radiation therapy (ISRT) 1
   • R-CHOP has shown a median overall survival of 50 months with 5-year OS rates of 66% in transformed follicular lymphoma (TFL) 1

2. Response evaluation:

   • For patients achieving complete response (CR) or partial response (PR):
     • Consider consolidation with HDT/ASCR ± ISRT (if not previously given) 1
     • Observation is an alternative option for selected patients 1
   • For patients with PR considering transplant:
     • Additional systemic therapy ± ISRT to induce CR 1
     • Note: Strongly consider repeat biopsy for PET-positive PR cases as PET positivity may represent post-treatment inflammation 1

3. Special considerations:

   • If transformation is coexisting with extensive FL and CR is achieved:
     • Consider rituximab maintenance 1
   • For patients with PR not proceeding to transplant:
     • Consider radioimmunotherapy (RIT) with ibritumomab tiuxetan or ISRT for localized/residual FDG-avid disease 1

For patients with transformation after multiple prior therapies:

1. Preferred approach:

   • Clinical trial enrollment (if available) 1

2. Alternative options:

   • Chemoimmunotherapy (with regimens recommended for second-line DLBCL) ± ISRT 1
   • Radioimmunotherapy with ibritumomab tiuxetan 1
   • ISRT alone (for localized disease) 1
   • CAR T-cell therapy (axicabtagene ciloleucel or tisagenlecleucel) for patients who have received ≥2 prior chemoimmunotherapy regimens 1

Special Considerations

Double-hit transformed lymphoma:

• TFL with double-hit cytogenetics (MYC with either BCL2 or BCL6 translocations) occurs in approximately 24% of patients 1
• These cases should be managed with more aggressive chemoimmunotherapy regimens as recommended for high-grade B-cell lymphoma with MYC and BCL2/BCL6 translocations 1
• This subtype has inferior survival compared to TFL without double-hit cytogenetics 1

Refractory disease management:

• For non-responsive or progressive disease:
  • CAR T-cell therapy (if ≥2 prior chemoimmunotherapy regimens) 1
  • Radioimmunotherapy with ibritumomab tiuxetan 1
  • Best supportive care 1

Prognostic Factors

Recent data from the rituximab era shows improved outcomes compared to historical cohorts:

• Treatment-naïve FL patients prior to transformation have significantly better outcomes than pretreated patients 2
• In a recent population-based study, post-transformation survival rate at 5 years was 49.6%, with a median post-transformation survival of 56 months 3
• Factors associated with worse post-transformation survival include:
  • Older age
  • Advanced stage
  • Early transformation
  • Prior chemotherapy or combined modality therapy before transformation 3

Important Caveats

1. Diagnosis confirmation: Always confirm transformation with an excisional or incisional lymph node biopsy rather than fine needle aspiration 1

2. Treatment selection: No randomized studies support a single optimal treatment approach for TFL, as clinical trials have often excluded this patient population 1

3. Transplant considerations: While retrospective studies suggest benefit from HDT/ASCR as consolidation, this has not been confirmed in prospective controlled studies 1

4. CAR T-cell therapy: For patients who have received CAR T-cell therapy, subsequent HDT/ASCR is not recommended, and allogeneic transplant remains investigational 1

5. Monitoring: Patients should be monitored closely after treatment for transformation as rare cases of reversion back to follicular lymphoma have been reported 4