First-line therapy with rituximab vs. rituximab-CHOP in post-transplant monomorphic diffuse large B-cell lymphoma (DLBCL): Long-term real-world evidence from the spanish group of lymphoma (GELTAMO) Free

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of immunosuppression-related conditions that develop in transplant recipients. Most of the PTLD are of B-cell origin, with diffuse large B-cell lymphoma (DLBCL) being the most common histology. The optimal upfront therapy for PTLD following solid organ transplantation, beyond immunosuppression reduction (RIS), involves a risk-stratified, sequential approach with rituximab with or without chemotherapy, using more aggressive therapeutic schemes for patients with higher risk disease. Long-term, real-world evidence on patients with DLBCL treated for PTLD is needed. We aimed to estimate overall survival in PTLD DLBCL subtype with a focus on outcomes of patients treated for PTLD without chemotherapy.

This is a retrospective study of patients diagnosed with post-transplant DLBCL between 2004 and 2024 in 21 Spanish hospitals. PTLD treatment was determined by physician preference. Follow-up time was calculated from PTLD diagnosis. Patient data included types of transplants, histology of PTLD, baseline demographics, clinical management approaches, response rates and survival outcomes. Overall survival (OS) was calculated from the time of PTLD diagnosis to the time of death, regardless of the cause. Univariate survival analysis was performed using the log-rank test, and multivariate analysis was performed using a Cox regression model.

A total of 304 patients with biopsy-proven DLBCL PTLD were registered in the GELTAMO database. Most of them were male (74.3%), had an advanced Ann Arbor stage (68%) and extranodal involvement (74.4%), the most common location, gastrointestinal (31.8%). B-symptoms were present only in 36% of patients. The most frequent organs transplanted were kidney (42.3%) liver (30.2%), heart (13.4%) and lung (8.5%). At diagnosis, 41.9% presented high-intermediate or high risk International Prognostic Index (IPI) score.

Median time from transplantation to PTLD diagnosis was 8.7 years. A total of 138 patients received upfront rituximab monotherapy (R-Mono) and 119 received rituximab-CHOP (R-CHOP). The median number of cycles was 4 (IQR 4-6) for R-Mono and 6 (IQR 4-6) for R-CHOP. Basal characteristics between both groups were not different (all p-values > 0.05) except for mycophenolate mofetil as organ rejection prophylaxis that was more frequent in R-CHOP (50.4% vs 26.1%, p< 0.001).

Overall response was 91.8% for R-CHOP and 74.8% for R-Mono; odds ratio 0.79 (95%CI 0.45-1.37), p=0.4); complete response was higher for R-CHOP (80.6% vs. 42.7%; odds ratio 4.15 (2.58-7.06), p< 0.001). Median follow-up of 7.5 years (range 0.87-23). Fifty percent of patients (69/138) in the R-mono group received R-CHOP because of not adequate control of the disease. The 5-year OS was 49.4% (40.7-60%) for R-Mono patients and 56.1% (47-67%) R-CHOP. OS did not differ (Hazard ratio 1.24 (0.87-1.78, p=0.2).

In a univariate analysis, age, low albumin and ECOG >2 worsened OS in both groups (all p-values <0.05). Nevertheless, extranodal involvement, more specifically liver and graft infiltration, high beta-2-microglobuline and bulky disease had a negative impact in OS only in R-mono patients.

The causes of death differed between R-Mono vs R-CHOP groups (p= 0.014): disease progression (52.9% vs. 30.8%), treatment-related toxicity (20% vs. 34.6%;), and transplant-related causes (28.8% vs. 27.1%), respectively. Noticeably only 2 patients (2.9%) in R-mono group died due to R-mono-related toxicity while the rest of the patients died because of second line R-CHOP toxicity after R-mono failure.

The IPI differentiated prognostic groups, with 5-year OS of 59.3% for low-risk (0-2 points) vs. 48.5% for high-risk (≥3 points) groups in the R-CHOP cohort, and 57.9% vs. 38.6% in the R-Mono cohort, respectively. OS was not different by initial treatment in subgroups defined by IPI (interaction term p-value=0.2)Conclusion: This is the largest real-world study of post-transplant monomorphic DLBCL, supporting rituximab monotherapy (R-Mono) as the initial treatment even for those with high-risk IPI.