Page 65 - Haematologica Vol. 107 - September 2022

ARTICLE - Acute Lymphoblastic Leukemia
Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and BCR-ABL-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin
Sabine Kayser,1,2 Chiara Sartor,3 Marlise R. Luskin,4 Jonathan Webster,5 Fabio Giglio,6 Nydia Panitz,1 Andrew M. Brunner,7 Matthias Fante,8 Christoph Lutz,9,10 Daniel Wolff,8 Anthony D. Ho,9 Mark J. Levis,5 Richard F. Schlenk2,9# and Cristina Papayannidis11#
1Medical Clinic and Policlinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany; 2NCT Trial Center, National Center of Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany; 3Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi, Bologna, Italy; 4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; 5Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; 6Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; 7Massachusetts General Hospital, Boston, MA, USA; 8Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Regensburg, Germany; 9Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany; 10Praxis for Hematology and Oncology Koblenz, Koblenz, Germany and 11IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli” Bologna, Italy.
#RFS and CP contributed equally as co-senior authors.
Abstract
Acute lymphoblastic leukemia (ALL) can relapse in the extramedullary compartment, with or without medullary involve- ment. Response to treatment may be individual. We evaluated response to inotuzumab ozogamicin in 31 patients with re- lapsed/refractory B-ALL with extramedullary disease. Median age was 31 years (range, 19-81). All patients were heavily pretreated, including allogeneic hematopoietic stem cell transplantation (HSCT; n=18). Overall response rate after two cycles of inotuzumab ozogamicin was 84% (complete remission, 55%; partial remission, 29%; resistant disease, 13%; early death, 3%). The median follow-up was 29 months and median overall survival was 12.8 months. One-year and 2-year overall survival rates were 53% (95% CI: 37-76%) and 18% (95% CI: 8-43%), respectively. Age had no impact on overall sur- vival when assessed as a continuous variable or dichotomized at 60 years. Twelve patients proceeded to allogeneic HSCT (complete remission, n=6; partial remission, n=3; resistant disease, n=3). Prior to allogeneic HSCT, eight patients received two or fewer cycles and four patients received three or four cycles of inotuzumab ozogamicin. Sinusoidal obstruction syndrome was reported in three patients, including one after transplantation. Allogeneic HSCT, evaluated as a time-de- pendent variable, had no impact on overall survival. Inotuzumab ozogamicin seems to be effective as a debulking strategy in relapsed/refractory ALL with extramedullary disease. However, inotuzumab ozogamicin followed by allogeneic HSCT seems not to be effective in maintaining long-term disease control.
Correspondence: S. Kayser s.kayser@dkfz-heidelberg.de
Received:
Accepted:
Prepublished:
. https://doi.org/10.3324/haematol.2021.280433
©2022 Ferrata Storti Foundation Published under a CC BY-NC license
November 29, 2021. February 1, 2022. February 10, 2022
Introduction
Historically, refractory/relapsed (r/r) B-cell acute lympho- blastic leukemia (B-ALL) in adults has a dismal prognosis, with less than 10% of patients being long-term survivors.1 At present, allogeneic hematopoietic stem cell transplan- tation (HSCT) is considered the only curative option for
patients with r/r B-ALL with best outcomes achieved after effective salvage re-induction therapy and transplantation in complete remission (CR) without measurable residual disease.2,3
The role of novel immune-based chimeric antigen recep- tor T-cell infusions in this setting has remained undefined.4-6 Although conventional salvage chemotherapy
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