Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment.
This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10(-4) blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months.
Amgen Research (Munich), Munich, Germany;
Gerhard
G
Zugmaier
Department of Medicine II, Goethe University Frankfurt, Frankfurt, Germany;
Nicola
N
Gökbuget
Amgen Research (Munich), Munich, Germany;
Matthias
M
Klinger
Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany;
Andreas
A
Viardot
Department of Medicine A, University of Münster, Münster, Germany;
Matthias
M
Stelljes
Department of Medicine II, Christian-Albrechts-Universität zu Kiel, Kiel, Germany;
Svenja
S
Neumann
Department of Medicine II, Christian-Albrechts-Universität zu Kiel, Kiel, Germany;
Heinz-A
HA
Horst
Department of Medicine I, Albert-Ludwigs-Universität Frieburg, Freiburg, Germany;
Reinhard
R
Marks
Department of Medicine II, Eberhard Karls Universität Tübingen, Tübingen, Germany;
Christoph
C
Faul
Department of Hematology and Oncology, Medizinische Hochschule Hannover, Hannover, Germany;
Helmut
H
Diedrich
Department of Medicine III, University of Regensburg, Regensburg, Germany;
Albrecht
A
Reichle
Department of Medicine II, Christian-Albrechts-Universität zu Kiel, Kiel, Germany;
Monika
M
Brüggemann
Amgen, Rockville, MD; and.
Chris
C
Holland
Amgen Research (Munich), Munich, Germany;
Margit
M
Schmidt
Department of Medicine II and.
Hermann
H
Einsele
Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany.
Ralf C
RC
Bargou
Department of Medicine II and.
Max S
MS
Topp
D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D016207:Cytokines / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology*; D055815:Young Adult
D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; C510808:blinatumomab