Treatment of Recurrent Diffuse Large B-Cell Lymphoma

Initial Diagnostic Workup and Treatment Algorithm

The European Society for Medical Oncology recommends that patients with recurrent DLBCL after rituximab-based anthracycline chemotherapy 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, for patients with good performance status and no major organ dysfunction 1, 2
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, according to the European Society for Medical Oncology 1, 2, 3
Patients amenable to curative therapy require complete restaging identical to initial diagnosis, including CT scan of chest and abdomen, bone marrow aspirate and biopsy, complete blood count, LDH, uric acid, HIV and hepatitis B/C screening, and cardiac function assessment, as recommended by the European Society for Medical Oncology 1, 2, 4, 5
The International Prognostic Index (IPI) calculation is necessary for patients with recurrent DLBCL, as recommended by the European Society for Medical Oncology 6

Rituximab-based salvage regimens (R-DHAP or R-ICE) demonstrate equivalent outcomes and either may be selected for transplant-eligible patients, according to the European Society for Medical Oncology 1, 2, 3
Patients achieving response to salvage therapy should proceed to high-dose chemotherapy with autologous stem cell support, as recommended by the European Society for Medical Oncology 1, 2, 3
Involved-field radiotherapy may be added for limited-stage disease, though this has never been evaluated in controlled trials, according to the European Society for Medical Oncology 1, 3

Patients unsuitable for high-dose therapy due to age (≥65-70 years), poor performance status, or major organ dysfunction should receive alternative salvage regimens such as R-GEMOX (rituximab, gemcitabine, oxaliplatin), as recommended by the European Society for Medical Oncology 1, 3
Combination with involved-field radiotherapy when appropriate is recommended for transplant-ineligible patients, according to the European Society for Medical Oncology 1, 3

Allogeneic transplantation following chemotherapy should be considered for patients with refractory disease to salvage therapy or early relapse (<12 months from initial treatment), as recommended by the European Society for Medical Oncology 1, 3
Tumor lysis syndrome prevention is necessary for patients with high tumor burden, and administer prednisone 100 mg orally for several days as "prephase" treatment before initiating salvage therapy, as recommended by the European Society for Medical Oncology 6, 5

Follow-up of patients achieving second remission mirrors first remission protocols, including history and physical examination every 3 months for 1 year, every 6 months for 2 years, then annually, as recommended by the European Society for Medical Oncology 1, 3

The European Society for Medical Oncology recognizes CAR T as an option following two lines of treatment, which this patient has received, with superior outcomes compared to autologous stem cell transplantation in early relapsed disease 7

Organ function requirements for CAR T-cell therapy include creatinine clearance ≥ 60 mL/min and cardiac ejection fraction ≥ 45% 7

For patients who relapsed after rituximab-containing first-line therapy, CAR T-cell therapy demonstrates better outcomes than the traditional ASCT pathway, with 3-year progression-free survival of only 23% in patients relapsing within 12 months 8
Even in favorable scenarios, CAR T is now considered equivalent or superior to ASCT based on recent evidence 7

Do not proceed directly to ASCT without considering CAR T first, as the evidence now favors CAR T in early relapsed disease 7