Nicola Gökbuget1, Hervé Dombret2, Sebastian Giebel3, Monika Bruggemann4, Michael Doubek5, Robin Foà6, Dieter Hoelzer1, Christopher Kim7, Giovanni Martinelli8, Elena Parovichnikova9, Alessandro Rambaldi10, Josep-Maria Ribera11, Marieke Schoonen12, Julia M Stieglmaier13, Gerhard Zugmaier13, Renato Bassan14. 1. a Department of Medicine II, Department of Hematology/Oncology , University Hospital , Frankfurt , Germany. 2. b Hôpital Saint-Louis, University Paris Diderot , Paris , France. 3. c Maria Sklodowska Curie Memorial Cancer Center , Gliwice , Poland. 4. d Department of Hematology and Oncology , University Hospital Schleswig-Holstein, Campus Kiel , Kiel , Germany. 5. e Department of Internal Medicine, Hematology and Oncology , University Hospital , Brno , Czech Republic. 6. f "Sapienza" University of Rome , Rome , Italy. 7. g Amgen Inc , Thousand Oaks , CA , USA. 8. h Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy. 9. i National Research Center for Hematology , Moscow , Russia. 10. j Dipartimento di Oncologia ed Ematologia , Università degli Studi di Milano and Ospedale Papa Giovanni XXIII , Bergamo , Italy. 11. k ICO-Hospital Germans Trias I Pujol, Josep Carreras Research Institute , Barcelona , Spain. 12. l Amgen Ltd , London , UK. 13. m Amgen GmBH , Munich , Germany. 14. n Ospedale dell'Angelo , Mestre-Venezia , Italy.
Abstract
OBJECTIVES: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10-4 Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000-2014. MRD was measured by polymerase chain reaction or flow cytometry. Patients were age ≥15 years at initial ALL diagnosis. Patients were excluded if exposed to blinatumomab within 18 months of baseline or prior alloHSCT. RESULTS: Of 272 patients in CR1, baseline MRD was ≥10-1, 10-2 to <10-1, 10-3 to <10-2, and 10-4 to <10-3 in 15 (6%), 71 (26%), 109 (40%), and 77 (28%) patients, respectively. Median duration of complete remission (DoR) was 18.5 months (95% confidence interval [CI], 11.9-27.2), median relapse-free survival (RFS) was 12.4 months (95% CI, 10.0-19.0) and median overall survival (OS) was 32.5 months (95% CI, 23.6-48.0). Lower baseline MRD level (P ≤ .0003) and white blood cell count <30,000/µL at diagnosis (P ≤ .0053) were strong predictors for better RFS and DoR. Allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with longer RFS (hazard ratio [HR], 0.59; 95% CI, 0.41-0.84) and DoR (HR, 0.43; 95% CI, 0.29-0.64); the association with OS was not significant (HR, 0.72; 95% CI, 0.50-1.05). DISCUSSION: In conclusion, RFS, DoR, and OS are relatively short in patients with MRD-positive ALL, particularly at higher MRD levels. AlloHSCT may improve survival but has limitations. Alternative approaches are needed to improve outcomes in MRD-positive ALL.
OBJECTIVES: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10-4 Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000-2014. MRD was measured by polymerase chain reaction or flow cytometry. Patients were age ≥15 years at initial ALL diagnosis. Patients were excluded if exposed to blinatumomab within 18 months of baseline or prior alloHSCT. RESULTS: Of 272 patients in CR1, baseline MRD was ≥10-1, 10-2 to <10-1, 10-3 to <10-2, and 10-4 to <10-3 in 15 (6%), 71 (26%), 109 (40%), and 77 (28%) patients, respectively. Median duration of complete remission (DoR) was 18.5 months (95% confidence interval [CI], 11.9-27.2), median relapse-free survival (RFS) was 12.4 months (95% CI, 10.0-19.0) and median overall survival (OS) was 32.5 months (95% CI, 23.6-48.0). Lower baseline MRD level (P ≤ .0003) and white blood cell count <30,000/µL at diagnosis (P ≤ .0053) were strong predictors for better RFS and DoR. Allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with longer RFS (hazard ratio [HR], 0.59; 95% CI, 0.41-0.84) and DoR (HR, 0.43; 95% CI, 0.29-0.64); the association with OS was not significant (HR, 0.72; 95% CI, 0.50-1.05). DISCUSSION: In conclusion, RFS, DoR, and OS are relatively short in patients with MRD-positive ALL, particularly at higher MRD levels. AlloHSCT may improve survival but has limitations. Alternative approaches are needed to improve outcomes in MRD-positive ALL.
Authors: Klaus Wethmar; Svenja Matern; Eva Eßeling; Linus Angenendt; Heike Pfeifer; Monika Brüggemann; Patrick Stelmach; Simon Call; Jörn C Albring; Jan-Henrik Mikesch; Christian Reicherts; Christoph Groth; Christoph Schliemann; Wolfgang E Berdel; Georg Lenz; Matthias Stelljes Journal: Bone Marrow Transplant Date: 2020-01-30 Impact factor: 5.483
Authors: Irene Della Starza; Sabina Chiaretti; Maria S De Propris; Loredana Elia; Marzia Cavalli; Lucia A De Novi; Roberta Soscia; Monica Messina; Antonella Vitale; Anna Guarini; Robin Foà Journal: Front Oncol Date: 2019-08-07 Impact factor: 6.244
Authors: Michael M Boyiadzis; Ivan Aksentijevich; Daniel A Arber; John Barrett; Renier J Brentjens; Jill Brufsky; Jorge Cortes; Marcos De Lima; Stephen J Forman; Ephraim J Fuchs; Linda J Fukas; Steven D Gore; Mark R Litzow; Jeffrey S Miller; John M Pagel; Edmund K Waller; Martin S Tallman Journal: J Immunother Cancer Date: 2020-10 Impact factor: 13.751