• This record comes from PubMed

Blinatumomab vs historic standard-of-care treatment for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukaemia

. 2020 Apr ; 104 (4) : 299-309. [epub] 20200124

Language English Country England, Great Britain Media print-electronic

Document type Journal Article

Grant support
Amgen (Europe) GmBH

OBJECTIVES: Survival outcomes from a single-arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)-positive B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set. METHODS: The primary analysis comprised adult Philadelphia chromosome (Ph)-negative patients in first complete haematologic remission (MRD ≥ 10-3 ). Relapse-free survival (RFS) and overall survival (OS) were compared between blinatumomab- and SOC-treatment groups. Baseline differences between groups were adjusted by propensity scores. RESULTS: The primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab-treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC-treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC. CONCLUSIONS: These analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD-positive Ph-negative BCP-ALL vs SOC.

Erratum In

PubMed

See more in PubMed

Brüggemann M, Kotrova M. Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Blood Adv. 2017;1:2456‐2466. PubMed PMC

Brüggemann M, Raff T, Kneba M. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood. 2012;120:4470‐4481. PubMed

Bassan R, Hoelzer D. Modern therapy of acute lymphoblastic leukemia. J Clin Oncol. 2011;29:532‐543. PubMed

Moppett J, Burke GA, Steward CG, Oakhill A, Goulden NJ. The clinical relevance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia. J Clin Pathol. 2003;56:249‐253. PubMed PMC

Brüggemann M, Schrauder A, Raff T, et al. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia. 2010;24:521‐535. PubMed

van Dongen JJ, van der Velden VH, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015;125:3996‐4009. PubMed PMC

Bassan R, Spinelli O, Oldani E, et al. Improved risk classification for risk‐specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood. 2009;113:4153‐4162. PubMed

Brüggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard‐risk acute lymphoblastic leukemia. Blood. 2006;107:1116‐1123. PubMed

Gökbuget N, Kneba M, Raff T, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120:1868‐1876. PubMed

Holowiecki J, Krawczyk‐Kulis M, Giebel S, et al. Status of minimal residual disease after induction predicts outcome in both standard and high‐risk Ph‐negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4–2002 MRD Study. Br J Haematol. 2008;142:227‐237. PubMed

Raff T, Gökbuget N, Luschen S, et al. Molecular relapse in adult standard‐risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood. 2007;109:910‐915. PubMed

Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B‐precursor acute lymphoblastic leukemia. Blood. 2018;131:1522‐1531. PubMed PMC

Berry DA, Zhou S, Higley H, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta‐analysis. JAMA Oncol. 2017;3:e170580. PubMed PMC

Brüggemann M, Gökbuget N, Kneba M. Acute lymphoblastic leukemia: monitoring minimal residual disease as a therapeutic principle. Semin Oncol. 2012;39:47‐57. PubMed

Mortuza FY, Papaioannou M, Moreira IM, et al. Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol. 2002;20:1094‐1104. PubMed

Beldjord K, Chevret S, Asnafi V, et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123:3739‐3749. PubMed

Pemmaraju N, Kantarjian H, Jorgensen JL, et al. Significance of recurrence of minimal residual disease detected by multi‐parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission. Am J Hematol. 2017;92:279‐285. PubMed PMC

Vidriales MB, Perez JJ, Lopez‐Berges MC, et al. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood. 2003;101:4695‐4700. PubMed

Ravandi F, Jorgensen JL, O'Brien SM, et al. Minimal residual disease assessed by multi‐parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia. Br J Haematol. 2016;172:392‐400. PubMed PMC

Ribera JM, Oriol A, Morgades M, et al. Treatment of high‐risk Philadelphia chromosome‐negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL‐AR‐03 trial. J Clin Oncol. 2014;32:1595‐1604. PubMed

Patel B, Rai L, Buck G, et al. Minimal residual disease is a significant predictor of treatment failure in non T‐lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol. 2010;148:80‐89. PubMed

Schrappe M. Detection and management of minimal residual disease in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2014;2014:244‐249. PubMed

Stein A, Forman SJ. Allogeneic transplantation for ALL in adults. Bone Marrow Transplant. 2008;41:439‐446. PubMed

National Comprehensive Cancer Network . NCCN clinical practice guidelines in oncology. Acute lymphoblastic leukemia. Version 1.2018 2018. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed October 2, 2019.

Hoelzer D, Bassan R, Dombret H, et al. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‐up. Ann Oncol. 2016;27:v69‐v82. PubMed

Dhedin N, Huynh A, Maury S, et al. Role of allogeneic stem cell transplantation in adult patients with Ph‐negative acute lymphoblastic leukemia. Blood. 2015;125:2486‐2496. PubMed

Eckert C, Henze G, Seeger K, et al. Use of allogeneic hematopoietic stem‐cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate‐risk group. J Clin Oncol. 2013;31:2736‐2742. PubMed

Spinelli O, Peruta B, Tosi M, et al. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high‐risk acute lymphoblastic leukemia. Haematologica. 2007;92:612‐618. PubMed

Zhou Y, Slack R, Jorgensen JL, et al. The effect of peritransplant minimal residual disease in adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2014;14:319‐326. PubMed PMC

Bassan R, Spinelli O, Oldani E, et al. Different molecular levels of post‐induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia‐negative acute lymphoblastic leukemia. Blood Cancer J. 2014;4:e225. PubMed PMC

Giebel S, Stella‐Holowiecka B, Krawczyk‐Kulis M, et al. Status of minimal residual disease determines outcome of autologous hematopoietic SCT in adult ALL. Bone Marrow Transplant. 2010;45:1095‐1101. PubMed

Bar M, Wood BL, Radich JP, et al. Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia. Leuk Res Treatment. 2014;2014:421723. PubMed PMC

Gokbuget N, Dombret H, Giebel S, et al. Minimal residual disease level predicts outcome in adults with Ph‐negative B‐precursor acute lymphoblastic leukemia. Hematology. 2019;24:337‐348. PubMed

Klinger M, Brandl C, Zugmaier G, et al. Immunopharmacologic response of patients with B‐lineage acute lymphoblastic leukemia to continuous infusion of T cell‐engaging CD19/CD3‐bispecific BiTE antibody blinatumomab. Blood. 2012;119:6226‐6233. PubMed

Topp MS, Kufer P, Gökbuget N, et al. Targeted therapy with the T‐cell‐engaging antibody blinatumomab of chemotherapy‐refractory minimal residual disease in B‐lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia‐free survival. J Clin Oncol. 2011;29:2493‐2498. PubMed

Topp MS, Gökbuget N, Zugmaier G, et al. Long‐term follow‐up of hematologic relapse‐free survival in a phase 2 study of blinatumomab in patients with MRD in B‐lineage ALL. Blood. 2012;120:5185‐5187. PubMed

Gökbuget N, Zugmaier G, Klinger M, et al. Long‐term relapse‐free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B‐lineage acute lymphoblastic leukemia. Haematologica. 2017;102:e132‐e135. PubMed PMC

Simon R, Blumenthal GM, Rothenberg ML, et al. The role of nonrandomized trials in the evaluation of oncology drugs. Clin Pharmacol Ther. 2015;97:502‐507. PubMed

Gökbuget N, Kelsh M, Chia V, et al. Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia. Blood Cancer J. 2016;6:e473. PubMed PMC

Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41‐55.

Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836‐847. PubMed PMC

Imbens GW. Nonparametric estimation of average treatment effects under exogenicity: a review. Rev Econ Stat. 2004;86:4‐29.

Jabbour E, Sasaki K, Ravandi F, et al. Chemoimmunotherapy with inotuzumab ozogamicin combined with mini‐hyper‐CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome‐negative acute lymphoblastic leukemia in first salvage. Cancer. 2018;124:4044‐4055. PubMed PMC

Sasaki K, Jabbour EJ, Ravandi F, et al. Hyper‐CVAD plus ponatinib versus hyper‐CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia: A propensity score analysis. Cancer. 2016;122:3650‐3656. PubMed PMC

Lim J, Walley R, Yuan J, et al. Minimizing patient burden through the use of historical subject‐level data in innovative confirmatory clinical trials: review of methods and opportunities. Ther Innov Regul Sci. 2018;52:546‐559. PubMed

Hirano K, Imbens GW, Ridder G. Efficient estimation of average treatment effects using the estimated propensity score. Econometrica. 2003;71:1161‐1189.

Choi S, Henderson MJ, Kwan E, et al. Relapse in children with acute lymphoblastic leukemia involving selection of a preexisting drug‐resistant subclone. Blood. 2007;110:632‐639. PubMed

Park JH, Riviere I, Gonen M, et al. Long‐term follow‐up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449‐459. PubMed PMC

Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B‐Cell lymphoblastic leukemia. N Engl J Med. 2018;378:439‐448. PubMed PMC

Rowe JM. Prognostic factors in adult acute lymphoblastic leukaemia. Br J Haematol. 2010;150:389‐405. PubMed

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...