Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients
Tim Strüßmann1, Philipp Hermes1, Gabriele Ihorst2
1Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Insights
Reduced intensity conditioning (RIC) before autologous stem cell transplantation (ASCT) is a feasible option for elderly diffuse large B-cell lymphoma patients, showing comparable outcomes to standard intensity conditioning (SIC) after adjusting for confounders.
Area of Science:
- Hematology
- Oncology
- Clinical Medicine
Background:
- High-dose chemotherapy followed by autologous stem cell transplantation (HDCT/ASCT) is a standard treatment for diffuse large B-cell lymphoma (DLBCL).
- HDCT/ASCT is associated with significant toxicity, particularly in elderly or medically frail patients.
- Reduced intensity conditioning (RIC) regimens have been developed to mitigate treatment-related morbidity.
Purpose of the Study:
- To evaluate the efficacy and safety of RIC compared to standard intensity conditioning (SIC) in elderly DLBCL patients undergoing ASCT.
- To identify factors influencing outcomes in this patient population.
Main Methods:
- Retrospective analysis of 146 DLBCL patients aged 60 years and older treated between 2005 and 2019.
- Patients were divided into two groups: 86 receiving SIC (BEAM/TEAM) and 60 receiving RIC (various regimens including BCNU, melphalan, thiotepa, busulfan, bendamustine).
- Comparison of toxicities, nonrelapse mortality (NRM), relapse rates, progression-free survival (PFS), and overall survival (OS).
Main Results:
- Toxicities were comparable between SIC and RIC groups.
- The 3-year cumulative incidence of relapse was higher in the RIC group (30.8%) compared to the SIC group (23.4%) (p=0.034).
- No significant difference in NRM was observed. Univariate analysis showed superior PFS with SIC, but multivariate analysis revealed no significant difference in PFS and a trend towards better OS with RIC.
- Factors predicting better OS included RIC, age 60-69, ECOG 0, non-bulky disease, and prior 1 line of therapy.
Conclusions:
- RIC prior to ASCT appears feasible in elderly DLBCL patients.
- While univariate analysis favored SIC for PFS, multivariate analysis suggested comparable PFS and a potential OS benefit for RIC when adjusted for confounders.
- Age, performance status, and disease characteristics significantly impact survival outcomes in elderly DLBCL patients undergoing ASCT.
Abstract:
High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B-cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high-dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow-up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression-free survival (PFS) (HR 1.80 CI 1.11-2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86-2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40-1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22-0.94, p = 0.032). Age 60-69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60-69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.
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