Impact of FLT3 Inhibitor Maintenance Therapy on Post-Transplant Outcomes in FLT3-Mutated AML Patients: A Real World Analysis from the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST)
Year: 2024
Type: conference-abstract
Abstract: Introduction: FLT3 is mutated in 30% of AML and is associated with poor prognosis due to frequent and early relapse, leading to poor outcomes even after allo-SCT. Clinical trials using post-transplant FLT3 inhibitors have demonstrated feasibility, safety, and encouraging outcomes. This study, conducted by the DRST, aims to assess the impact of FLT3 inhibitors on the outcomes in a large cohort of FLT3-mutated AML patients post allo-HCT. Patients and Methods: We identified 923 patients (52% male, 48% female) who underwent allo-SCT for, HLA compatible donors between the years 2011-2023 for FLT3-mutated and were reported to DRST. The median age at transplant was 54 years (range 18-77). Seventy percent had a Karnofsky index >80%. The median time from diagnosis to transplant was 120 days (range 37-789). Ninety-five percent received PBSC grafts, and 51% underwent myeloablative conditioning. All patients were transplanted in CR1; 21% were MRD+, 24% were MRD-, and 55% had unknown MRD status. Thirteen percent (n=123) received mainly off-label use of FLT3-inhibitor maintenance after allo-SCT (41% Sorafenib, 34% Midostaurin, 3% Gilteritinib, 22% unknown), while 43% (n=400) did not and in 43% (n=400) it was unknown. Results: The 5-year relapse-free (RFS) and overall survival (OS) for the entire population was 53% (95% CI [49; 57]) and 62% (95% CI [58; 66]), respectively. Patients receiving maintenance therapy had statistically significant higher RFS with HR 2.1 (95% CI [1.4; 3.2], p<0.0001) and 5-year RFS 70% (95% CI [61; 80]) vs. 47% (95% CI [42; 54]), as well as OS (HR 2.9 (95% CI [1.7; 4.9]), p<0.0001, 5-year OS 81% (95% CI [73; 91]) vs. 57% (95% CI [51; 63])). Graft-versus-host disease relapse-free survival (GRFS) was significantly improved with maintenance therapy: HR 1.6 (95% CI [1.2; 2.2], p=0.0024) and 5-year GRFS 45% (95% CI [35; 58]) vs. 33% (95% CI [27; 39]). Non-relapse mortality (NRM) was significantly lower in the maintenance group (HR 4.8 (95% CI [1.8; 13.1]), p=0.002) with 5-year NRM 4% (95% CI [0; 8]) vs. 19% (95% CI [15; 24]). The cumulative incidence of relapse (CIR) at 5 years was comparable between both groups: 26% (95% CI [17; 35]) vs. 33% (95% CI [28; 39]), and the CIR over time was not statistically significant but with a positive impact of maintenance therapy (HR 1.5 (95% CI [1.0; 2.2]), p=0.078). In subgroup analysis based on MRD status, both MRD+ and MRD- subgroups showed improved OS and RFS with maintenance therapy. MRD positive patients had a 5-year OS of 75% (95% CI [60; 92]) with maintenance vs. 52% (95% CI [41; 67]) without (HR 2.8 (95% CI [1.3; 5.8]), p=0.0034), and a 5-year RFS of 64% (95% CI [50; 82]) with maintenance vs. 44% (95% CI [34; 57]) without (HR 1.9 (95% CI [1.0; 3.4]), p=0.0273). MRD negative patients had a 5-year OS of 87% (95% CI [76; 98]) with maintenance vs. 58% (95% CI [49; 69]) without (HR 3.4 (95% CI, [1.4; 8.5]), p=0.0021), and a 5-year RFS of 77% (95% CI [65; 92]) with maintenance vs. 45% (95% CI [36; 56]) without (HR 2.8 (95% CI [1.4; 5.6]), p=0.0010). There were no statistically significant differences in CIR, but a positive impact of maintenance therapy in both, MRD+ and MRD- subgroups. NRM was comparable in the MRD+ group, but MRD- patients receiving maintenance had lower NRM (5-year NRM 3% (95% CI [0; 7])) compared to those who did not (5-year NRM 23% (95% CI [15; 31]), HR 8.4 (95% CI [1.1; 62.6]), p=0.0380). There were no statistically significant differences in GRFS for MRD+ patients, while MRD- patients showed higher GRFS with maintenance (5-year GRFS 54% (95% CI [38; 77])) vs. without (5-year GRFS 37% (95% CI [29; 48]), HR 1.9 (95% CI [1.1; 3.3]), p=0.0091). Conclusion: Real world data from a large national registry showed that maintenance therapy with FLT3 inhibitors significantly improves RFS and OS in FLT3-mutated AML patients, irrespective of MRD status.
Source: Blood
Authors: Radwan Massoud, Sarah Flossdorf, Franziska Hanke, Thomas Schroeder, Wolfgang Andreas Bethge, Robert Zeiser, Caroline Pabst, Gerald Wulf, Elisa Sala, Inken Hilgendorf, Christof Scheid, Matthias Edinger, Friedrich Stölzel, Igor Wolfgang Blau, Matthias Stelljes, Guido Kobbe, Uwe Platzbecker, Jörg Bittenbring, Matthias Eder, Katharina Fleischhauer, Andreas Burchert, Christoph Schmid, Nicolaus Kroeger
Institutions: University Medical Center Hamburg-Eppendorf, Institut für Medizinische Informatik, Biometrie und Epidemiologie, University of Duisburg-Essen, Essen University Hospital, Universitätsklinikum Tübingen, University of Tübingen, University of Freiburg, University Hospital Heidelberg, Universitätsmedizin Göttingen, University of Göttingen, University Hospital Ulm, Jena University Hospital, University Hospital Cologne, University Hospital Regensburg, University Hospital Schleswig-Holstein, Charité - Universitätsmedizin Berlin, University of Münster, Düsseldorf University Hospital, University Hospital Leipzig, Leipzig University, Universitätsklinikum des Saarlandes, Medizinische Hochschule Hannover, Universitätsklinikum Gießen und Marburg, University Hospital Augsburg
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4405034811