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)

Massoud, Radwan

Oral and Poster Abstracts
732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II

Research, Adult, Acute Myeloid Malignancies, AML, Clinical Practice (Health Services and Quality), Clinical Research, Diseases, Real-world evidence, Registries, Myeloid Malignancies, Human, Study Population, Measurable Residual Disease

Radwan Massoud, MD, BS¹^*, Sarah Flossdorf²^*, Franziska Hanke³^*, Thomas Schroeder⁴^*, Wolfgang Andreas Bethge, MD⁵^*, Robert Zeiser, MD⁶, Caroline Pabst⁷^*, Gerald Wulf⁸^*, Elisa Sala⁹^*, Inken Hilgendorf, MD¹⁰^*, Christof Scheid, MD¹¹, Matthias Edinger, MD¹²^*, Friedrich Stölzel¹³^*, Igor Wolfgang Blau, MD, PhD¹⁴^*, Matthias Stelljes, MD¹⁵, Guido Kobbe, MD¹⁶^*, Uwe Platzbecker, MD¹⁷, Jörg Bittenbring¹⁸^*, Matthias Eder, MD¹⁹^*, Katharina Fleischhauer, MD²⁰^*, Andreas Burchert, MD²¹, Christoph Schmid, MD²²^* and Nicolaus Kroeger²³

¹Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Hamburg, Germany
²Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany
³German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST), Ulm, Germany
⁴Dept. of Hematology and Stem Cell Transplantation West German Cancer Centre University Hospital Essen Essen, Germany, Duisburg, Germany
⁵Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Tübingen, Germany
⁶University of Freiburg, Faculty of Medicine, Albert Ludwigs University (ALU), Freiburg, Germany, Freiburg, Germany, Freiburg, Germany
⁷University Hospital Heidleberg, Heidelberg, DEU
⁸Department of Hematology and Medical Oncology, University Hospital Goettingen, Goettingen, Germany
⁹Department of Internal Medicine , Hematology and Oncology, University Hospital of Ulm, Ulm, Germany
¹⁰Department of Internal Medicine , Hematology and Oncology, University Hospital Jena , Germany., Jena, Germany
¹¹Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany, Cologne, Germany
¹²Internal Medicine III - Hematology and Oncology, University Hospital Regensburg, Regensburg, DEU
¹³Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein, Kiel, Germany
¹⁴Medical Clinic, Charité University Medicine Berlin, Berlin, Germany, Berlin, Germany
¹⁵Department of Medicine A (Hematology, Hemostaseology, Oncology, Pneumology), University of Muenster, Muenster, Germany
¹⁶Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany
¹⁷Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany
¹⁸Department of Internal Medicine , Hematology and Oncology, University Hospital Homburg , Germany, Homburg/Saar, DEU
¹⁹Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
²⁰Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, Germany
²¹Department of Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany
²²Department of Hematology, University Hospital Augsburg, Augsburg, Germany
²³Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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.

Disclosures: Zeiser: Ironwood Pharmaceuticals, Inc.: Consultancy; Neovii: Consultancy; Medac: Honoraria; Sanofi: Honoraria; Mallinkrodt: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Platzbecker: Janssen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Amgen: Consultancy, Research Funding; Curis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Research Funding; Geron: Consultancy; Novartis: Consultancy, Research Funding. Kroeger: DKMS: Research Funding; Alexion, Therakos: Other: Speaker honorarium; BMS: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Neovii, Sanofi, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: speaker honorarium.

See more of: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II
See more of: Oral and Poster Abstracts

<< Previous Abstract | Next Abstract >>

^*signifies non-member of ASH

3560 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)