Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study.
Adolescent
Adult
Aged
Antibodies, Bispecific
/ pharmacology
Antineoplastic Agents
/ pharmacology
Female
Hematopoietic Stem Cell Transplantation
/ methods
Humans
Male
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Survival Rate
Transplantation Conditioning
/ methods
Young Adult
acute lymphoblastic leukemia
blinatumomab
refractory
relapsed
transplantation
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 Dec 2019
01 Dec 2019
Historique:
received:
28
01
2019
revised:
23
04
2019
accepted:
20
05
2019
pubmed:
23
8
2019
medline:
4
6
2020
entrez:
22
8
2019
Statut:
ppublish
Résumé
Blinatumomab, a bispecific T-cell-engaging (BiTE®) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P = .68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status. Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.
Sections du résumé
BACKGROUND
BACKGROUND
Blinatumomab, a bispecific T-cell-engaging (BiTE®) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab.
METHODS
METHODS
In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT.
RESULTS
RESULTS
Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P = .68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status.
CONCLUSIONS
CONCLUSIONS
Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab.
LAY SUMMARY
BACKGROUND
Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.
Substances chimiques
Antibodies, Bispecific
0
Antineoplastic Agents
0
blinatumomab
4FR53SIF3A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4181-4192Subventions
Organisme : Amgen Inc
ID : N/A
Informations de copyright
© 2019 American Cancer Society.
Références
Jabbour E, O’Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer. 2015;121:2517-2528.
Kansagra A, Dahiya S, Litzow M. Continuing challenges and current issues in acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59:526-541.
Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541-1552.
Gokbuget 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.
Lussana F, Intermesoli T, Gianni F, et al. Achieving molecular remission before allogeneic stem cell transplantation in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: impact on relapse and long-term outcome. Biol Blood Marrow Transplant. 2016;22:1983-1987.
Pulsipher MA, Carlson C, Langholz B, et al. IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients. Blood. 2015;125:3501-3508.
Zhang M, Fu H, Lai X, et al. Minimal residual disease at first achievement of complete remission predicts outcome in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia. PLoS One. 2016;11:e0163599.
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.
Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35:1795-1802.
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.
Topp MS, Gokbuget 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.
Topp MS, Gokbuget N, Zugmaier G, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32:4134-4140.
Kantarjian H, Stein A, Gokbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-847.
Simon R, Makuch RW. A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias. Stat Med. 1984;3:35-44.
Mantel N, Byar D. Evaluation of response-time data involving transient states: an illustration using heart-transplant data. J Am Stat Assoc. 1974;69:81-86.
Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507-1517.
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.
Gokbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131:1522-1531.
Zugmaier G, Gokbuget 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.
Kebriaei P, Stelljes M, DeAngelo D, et al. Role of remission status and prior transplant in optimizing survival outcomes following allogeneic hematopoietic stem transplantation (HSCT) in patients who received inotuzumab ozogamicin (INO) for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Blood. 2017;130:886.
Kebriaei P, Stelljes M, DeAngelo DJ, et al. Role of remission status and prior transplant in optimizing survival outcomes following allogeneic hematopoietic stem transplantation (HSCT) in patients who received inotuzumab ozogamicin for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). Biol Blood Marrow Transplant. 2018;24:S25-S118.
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. 2017;123:294-302.
Shalabi H, Delbrook C, Stetler-Stevenson M, et al. Chimeric antigen receptor T-cell (CAR-T) therapy can render patients with ALL into PCR-negative remission and can be an effective bridge to transplant (HCT). Poster [poster 1017] presented at: 2018 American Society of Pediatric Hematology/Oncology Conference; May 2-5, 2018; Pittsburgh, PA.
Leonard JT, Hayes-Lattin B. Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia; current evidence, and improving outcomes going forward. Curr Hematol Malig Rep. 2018;13:329-340.
Kebriaei P, Cutler C, de Lima M, et al. Management of important adverse events associated with inotuzumab ozogamicin: expert panel review. Bone Marrow Transplant. 2018;53:449-456.
Kantarjian HM, DeAngelo DJ, Advani AS, et al. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017;4:e387-e398.