Autologous Transplantation Improves Survival Rates for Follicular Lymphoma Patients Who Relapse within 2-Years of Chemoimmunotherapy: A Multi-Centre Retrospective Analysis of Consecutively Treated Patients in the Real World

Introduction: Although rituximab-based chemoimmunotherapy (RChemo) significantly improves overall survival (OS) for follicular lymphoma (FL), approximately 20% of patients experience initial time to progression (TTP1) of ≤2 years (early relapse) and relatively poor OS. We conducted a retrospective study to evaluate OS rates for patients with early relapse who were treated with or without high dose therapy and autologous stem cell transplantation (ASCT).

Methods: A retrospective, multi-centre, study was conducted to identify all patients aged 18 to 70 years who were consecutively diagnosed in Alberta with grade 1 to 3a FL prior to 2011, and eventually received RChemo as their initial systemic therapy. Patient characteristics including Follicular Lymphoma International Prognostic Index (FLIPI) factors at RChemo, treatment details including Rituximab-maintenance (RMaintenance), TTP post-RChemo, frequency of transformation at relapse, and treatments after relapse were obtained. TTP and OS following RChemo and ASCT were evaluated in univariate and multivariate analyses.

Results: Interrogation of the Alberta Cancer Registry identified 397 patients diagnosed with FL prior to 2011 who received RChemo. At a median follow-up of 92 months (3-179), 148 (37.3%) of the 397 patients relapsed from RChemo, including 82 (20.7%) with early relapse ≤2years and 66 (16.6%) with late relapse >2years.

Table 1.0 lists characteristics of the 148 patients who relapsed after RChemo. Seventy-one (48.0%) patients underwent ASCT at relapse. Conditioning regimens included high dose melphalan (n=49, 69%, of whom 35 also received total body irradiation), BEAM (carmustine, etoposide, cytarabine, melphalan, n=21, 29.6%), and CBV (cyclophosphamide, BCNU, VP-16, n=1, 1.4%). In total, there were 29.1% (n=43) deaths following relapse, with majority of deaths due to FL (n=32, 74.4%).

The projected 10-year OS following first RChemo was 93.8% in those with no relapse, 76.4% with late relapse, and 56.9% with early relapse (logrank p<0.001). Of the 71 patients who received ASCT, the 5-year TTP post-ASCT was 66.8% vs 70.6% for early (n=44) vs late (n=27) relapse patients, respectively (logrank p=0.85). Although the use of ASCT was not associated with OS for patients with late relapse (p=0.72), OS was superior for early relapse patients who received ASCT compared to those who did not receive ASCT (Figure 1.0) with 5-year OS rates of 86.0% vs 57.0%, respectively (HR 0.36, 95%CI 0.16-0.71, logrank p=0.005). Of note, relapse after RMaintenance vs no prior RMaintenance was not associated with OS (p=0.55). Table 2.0 lists the only factors that were associated with OS for patients with early relapse after RChemo in both univariate and multivariate analyses. The use of ASCT remained independently associated with improved OS for patients who relapsed <2 years of RChemo even when controlling for the other significant factors, which included baseline high risk FLIPI and transformation at relapse. Similar results were found when analyzed from time of first relapse following RChemo instead of from the time of first RChemo.

Conclusions: Our study strongly suggests that the use of ASCT for FL patients who relapse within 2 years of RChemo is associated with improved OS.

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