Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Arie Barlev, Vincent W Lin, Aaron Katz, Kuolung Hu, Ze Cong, Beth Barber, Arie Barlev, Vincent W Lin, Aaron Katz, Kuolung Hu, Ze Cong, Beth Barber

Abstract

Introduction: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results: At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions: These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(-) B-precursor ALL compared with salvage chemotherapy.

Funding: Amgen.

Trial registration: ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

Keywords: Acute lymphoblastic leukemia; Blinatumomab; Hematology; Long-term survival; Oncology.

Figures

Fig. 1
Fig. 1
5-year survival curves for patients receiving blinatumomab and historical dataset
Fig. 2
Fig. 2
Validation based on 36 months of observed data from the blinatumomab clinical trial

References

    1. Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944–950. doi: 10.1182/blood-2006-05-018192.
    1. O’Brien S, Thomas D, Ravandi F, et al. Outcome of adults with acute lymphocytic leukemia after second salvage therapy. Cancer. 2008;113:3186–3191. doi: 10.1002/cncr.23919.
    1. Kantarjian HM, Thomas D, Ravandi F, et al. Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration. Cancer. 2010;116:5568–5574. doi: 10.1002/cncr.25354.
    1. Gokbuget N, Stanze D, Beck J, et al. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012;120:2032–2041. doi: 10.1182/blood-2011-12-399287.
    1. Kenderian SS, Al-Kali A, Gangat N, et al. Monosomal karyotype in Philadelphia chromosome-negative acute lymphoblastic leukemia. Blood Cancer J. 2013;3:e122. doi: 10.1038/bcj.2013.21.
    1. Maury S, Huguet F, Leguay T, et al. Adverse prognostic significance of CD20 expression in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Haematologica. 2010;2:324–328. doi: 10.3324/haematol.2009.010306.
    1. Katz AJ, Chia VM, Schoonen WM, Kelsh MA. Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. Cancer Causes Control. 2015;11:1627–1642. doi: 10.1007/s10552-015-0657-6.
    1. Barlev A, Lin VW, Song X. Burden of hospitalization in relapsed acute lymphoblastic leukemia. Curr Med Res Opin. 2016. [Epub ahead of print].
    1. Dombret H, Thomas X, Chevallier P, et al. Healthcare burden and economic cost of hospitalisation during chemotherapy for adult patients with Ph-negative B-precursor relapsed or refractory (R/R) acute lymphoblastic leukaemia (ALL) in France. Value Health. 2015;18:A443. doi: 10.1016/j.jval.2015.09.1093.
    1. Kreuzer K, Stuhlmann R, Lebioda A, Reitan J, Barber B, Barlev A. Hospitalisations among adult patients with Ph-negative B-precursor relapsed or refractory (R/R) acute lymphoblastic leukaemia (ALL) receiving chemotherapy in Germany: a retrospective chart review. Value Health. 2015;18:A443. doi: 10.1016/j.jval.2015.09.1096.
    1. Pagano L, Oberti M, Esposito B, Reitan J, Barlev A, Barber B, Ferrara F. Retrospective chart review of hospitalisations during chemotherapy for adult patients with Ph-negative B-precursor relapsed or refractory (R/R) acute lymphoblastic leukaemia (ALL) in Italy. Value Health. 2015;18:A443. doi: 10.1016/j.jval.2015.09.1094.
    1. Blinatumomab USPI: . Accessed 5 May 2016.
    1. Blinatumomab EPAR: . Accessed 25 Feb 2016.
    1. Topp MS, Gokbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16:57–66. doi: 10.1016/S1470-2045(14)71170-2.
    1. Gökbuget N, Kelsh M, Chia V, et al. Blinatumomab versus historical standard therapy of adult relapsed/refractory acute lymphoblastic leukaemia. Blood Cancer J Blood Cancer J. 2016;6(9):e473. doi: 10.1038/bcj.2016.84.
    1. Latimer NR. Survival analysis for economic evaluations alongside clinical trials—extrapolation with patient-level data: inconsistencies, limitations, and a practical guide. Med Decis Making. 2013;33:743–754. doi: 10.1177/0272989X12472398.
    1. Demiris N, Sharples LD. Bayesian evidence synthesis to extrapolate survival estimates in cost-effectiveness studies. Stat Med. 2006;25:1960–1975. doi: 10.1002/sim.2366.
    1. Drummond M, Sculpher MJ, Torrance GW, O’Brien BJ, Stoddart GL. Methods for the economic evaluation of health care programmes. 3. Oxford: Oxford University Press; 2005.
    1. Pui CH, Carroll WL, Meshinchi S, Arceci RJ. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol. 2011;29:551–565. doi: 10.1200/JCO.2010.30.7405.
    1. Hoelzer D. Monitoring and managing minimal residual disease in acute lymphoblastic leukemia. Am Soc Clin Oncol Educ Book. 2013:290–93.
    1. Zugmaier G, Gökbuget N, Klinger M, et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood. 2015;126:2578–2584. doi: 10.1182/blood-2015-06-649111.
    1. Jabbour E, Short NJ, Jorgensen JL, et al. Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Cancer. 2016. [Epub ahead of print].
    1. 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. doi: 10.1111/bjh.13834.
    1. Gökbuget N, Dombret H, Bonifacio M, et al. Long-term outcomes after blinatumomab treatment: follow-up of a phase 2 study in patients (pts) with minimal residual disease (MRD) positive B-cell precursor acute lymphoblastic leukemia (ALL) Blood. 2015;126:680.
    1. 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. doi: 10.1182/blood-2012-07-441030.
    1. Topp MS, Stein A, Gökbuget N, Fielding AK, Schuh A, Ribera JM, et al. Blinatumomab improved overall survival in patients with relapsed or refractory Philadelphia negative B-cell precursor acute lymphoblastic leukemia in a randomized, open-label phase 3 study (TOWER) Haematologica. 2016;101(s1):S149.

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