What is the best salvage therapy for a 45-year-old patient with Diffuse Large B-Cell Lymphoma (DLBCL) who had a partial response to R-CHP (Rituximab (rituximab)-Cyclophosphamide (cyclophosphamide)-Doxorubicin (doxorubicin)-Prednisone (prednisone)) chemotherapy?

Best Salvage Therapy for Relapsed DLBCL After R-CHP

For this 45-year-old patient with partial response to R-CHP, the best salvage therapy is a rituximab-based platinum regimen (either R-DHAP or R-ICE) followed by high-dose chemotherapy with autologous stem cell transplant (ASCT) if chemosensitive response is achieved. 1

Critical Initial Assessment

Before initiating salvage therapy, this patient requires:

• Histological confirmation is mandatory since the initial response was only partial (not complete remission), to verify CD20 positivity and confirm DLBCL histology rather than transformation 1
• Complete restaging identical to initial diagnosis: CT chest/abdomen, bone marrow biopsy, CBC, LDH, cardiac function assessment 1
• International Prognostic Index (IPI) recalculation 1
• Geriatric assessment is not needed at age 45, but performance status and organ function must be adequate (no major organ dysfunction) 2

Recommended Salvage Regimen

Either R-DHAP or R-ICE should be selected, as they demonstrate equivalent efficacy with no survival difference between the two regimens 2, 1, 3:

• R-DHAP: Rituximab + dexamethasone + high-dose cytarabine + cisplatin
• R-ICE: Rituximab + ifosfamide + carboplatin + etoposide

The CORAL study definitively established equivalence between these regimens, showing similar response rates (R-ICE 63.5% vs R-DHAP 62.8%) and identical 3-year event-free survival 3. Choose R-DHAP if concerned about neurotoxicity from ifosfamide, or R-ICE if renal function is compromised (cisplatin in R-DHAP is nephrotoxic) 2.

Treatment Algorithm

Step 1: Administer 3 cycles of chosen salvage regimen

• Rituximab is included despite prior R-CHP exposure 2
• Response assessment after 2-3 cycles 2

Step 2: Proceed to ASCT if chemosensitive

• Only patients achieving complete or partial response to salvage therapy should proceed to high-dose therapy with ASCT 2, 1
• BEAM (carmustine, etoposide, cytarabine, melphalan) is the most commonly used conditioning regimen 2
• Consider involved-field radiotherapy for limited-stage disease, though this lacks controlled trial evidence 2, 1

Step 3: If no response to salvage therapy

• Consider allogeneic stem cell transplantation for patients with refractory disease to salvage therapy 2, 1
• Clinical trial enrollment is strongly recommended 2

Critical Prognostic Factors

This patient's outcome depends heavily on three factors 3:

1. Time to relapse/progression: Partial response (not CR) to first-line therapy predicts poor outcome—only 45% achieve long-term remission with salvage therapy 4
2. Prior rituximab exposure: Reduces 3-year event-free survival from 47% (rituximab-naive) to 21% (prior rituximab) 3
3. IPI score at relapse: IPI 2-3 yields 18% 3-year EFS vs 40% for IPI 0-1 3

The combination of partial response to R-CHP and prior rituximab exposure places this patient in a high-risk category, with expected 3-year event-free survival of approximately 20-30% even with optimal salvage therapy and ASCT 3, 4.

Essential Supportive Measures

• Administer prednisone 100 mg orally for several days as "prephase" treatment if high tumor burden exists, to prevent tumor lysis syndrome 1
• Ensure adequate hydration and consider allopurinol prophylaxis 1
• Prophylactic G-CSF is indicated to maintain dose intensity 2

Common Pitfalls to Avoid

• Do not delay histological confirmation—transformation or alternative diagnoses occur in late relapses 1
• Do not proceed to ASCT without documented chemosensitive response to salvage therapy—outcomes are dismal without response 4
• Do not use non-platinum salvage regimens (R-GEMOX, bendamustine) in transplant-eligible patients, as these are reserved for transplant-ineligible patients 2, 1
• Do not omit rituximab from salvage therapy despite prior exposure—phase II data suggest benefit even after rituximab-containing first-line therapy 2

Alternative if Transplant-Ineligible

If this patient develops contraindications to ASCT (organ dysfunction, poor performance status), alternative salvage regimens include R-GEMOX (rituximab, gemcitabine, oxaliplatin) combined with involved-field radiotherapy 2, 1.