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Alig, Stefan; Jurinovic, Vindi; Esfahani, Mohammad Shahrokh; Haebe, Sarah; Passerini, Verena; Hellmuth, Johannes C.; Gaitzsch, Erik; Keay, William; Tahiri, Natyra; Zoellner, Anna-Katharina; Rosenwald, Andreas; Klapper, Wolfram; Stein, Harald; Feller, Alfred C.; Ott, German; Staiger, Annette M.; Horn, Heike; Hansmann, Martin-Leo; Pott, Christiane; Unterhalt, Michael; Schmidt, Christian; Dreyling, Martin; Alizadeh, Ash A.; Hiddemann, Wolfgang; Hoster, Eva; Weigert, Oliver (22. September 2020): Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models. In: Blood Advances, Vol. 4, No. 18: pp. 4451-4462
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Abstract

High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months-prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.