What are the treatment options for a patient with recurrent diffuse large B cell lymphoma?

Treatment of Recurrent Diffuse Large B-Cell Lymphoma

For patients with recurrent DLBCL after rituximab-based anthracycline chemotherapy, eligible candidates (age <65-70 years, good performance status, no major organ dysfunction) should receive rituximab plus salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell transplant, while transplant-ineligible patients should receive alternative salvage regimens with or without radiotherapy. 1

Initial Diagnostic Workup at Relapse

Histological confirmation is mandatory for relapses occurring >12 months after initial diagnosis to verify CD20 positivity and confirm DLBCL histology, as transformation or alternative diagnoses may occur. 1 Image-guided core biopsy is appropriate when excisional biopsy is not feasible. 1

Patients amenable to curative therapy require complete restaging identical to initial diagnosis, including: 1

• CT scan of chest and abdomen
• Bone marrow aspirate and biopsy
• Complete blood count, LDH, uric acid
• HIV and hepatitis B/C screening
• Cardiac function assessment (LVEF) if further anthracyclines are planned
• International Prognostic Index (IPI) calculation

Treatment Algorithm for Transplant-Eligible Patients

Salvage Chemotherapy Selection

Rituximab-based salvage regimens (R-DHAP or R-ICE) demonstrate equivalent outcomes and either may be selected. 1 Both regimens include:

• R-DHAP: rituximab, cisplatin, cytosine arabinoside, dexamethasone 1
• R-ICE: rituximab, ifosfamide, carboplatin, etoposide 1

A potential advantage exists for R-DHAP in germinal center B-cell-like subtype, though this requires confirmation. 1

High-Dose Consolidation

Patients achieving response to salvage therapy should proceed to high-dose chemotherapy with autologous stem cell support. 1 BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan) represents the most frequently used high-dose regimen. 1

Involved-field radiotherapy may be added for limited-stage disease, though this has never been evaluated in controlled trials. 1

Rituximab maintenance after transplant is not recommended in responding patients. 1

Response Assessment Timing

Evaluation should occur after 3-4 cycles of salvage therapy (before high-dose treatment) and after completion of all therapy. 1 PET results before high-dose treatment correlate with clinical outcome. 1

Treatment for Transplant-Ineligible Patients

Patients unsuitable for high-dose therapy due to age (≥65-70 years), poor performance status, or major organ dysfunction should receive: 1

• Alternative salvage regimens such as R-GEMOX (rituximab, gemcitabine, oxaliplatin) 1
• Combination with involved-field radiotherapy when appropriate 1
• Preferential enrollment in clinical trials testing novel agents 1

Special Considerations for Refractory or Multiple Relapses

Allogeneic transplantation following chemotherapy should be considered for patients with: 1

• Refractory disease to salvage therapy
• Early relapse (<12 months from initial treatment)
• Relapse after autologous stem cell transplant

Recent evidence suggests CAR T-cell therapy demonstrates superior outcomes for patients with primary refractory or early-relapsed disease (within 12 months), with complete response rates of 40-58% and long-term disease-free survival >40%. 2, 3 For second relapse, CAR T-cell or CD3xCD20 bispecific antibody therapy is recommended in eligible patients. 2

Critical Pitfalls to Avoid

Do not omit histological confirmation for late relapses (>12 months), as CD20 status may change and alternative diagnoses must be excluded. 1

Do not add rituximab to salvage regimens in patients refractory to prior rituximab-containing therapy, as benefit is unlikely. 1

Avoid dose reductions of salvage chemotherapy for hematological toxicity unless absolutely necessary, as this compromises curative potential. 1

Do not use rituximab maintenance after autologous transplant, as this provides no benefit. 1

Tumor Lysis Syndrome Prevention

In patients with high tumor burden, administer prednisone 100 mg orally for several days as "prephase" treatment before initiating salvage therapy to prevent tumor lysis syndrome. 1, 4 Ensure adequate hydration and consider prophylactic allopurinol or rasburicase for highest-risk patients. 4

Follow-Up After Second Remission

Follow-up of patients achieving second remission mirrors first remission protocols: 1

• History and physical examination every 3 months for 1 year, every 6 months for 2 years, then annually
• Blood count and LDH at 3,6,12, and 24 months
• CT imaging at 6,12, and 24 months (routine PET surveillance not recommended)