Sequencing of novel agents in relapsed/refractory B-cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia.
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Bispecific
/ administration & dosage
Antineoplastic Agents, Immunological
/ administration & dosage
Drug Administration Schedule
Drug Resistance, Neoplasm
Female
Hematopoietic Stem Cell Transplantation
/ statistics & numerical data
Humans
Inotuzumab Ozogamicin
/ administration & dosage
Male
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Remission Induction
Retrospective Studies
Treatment Outcome
Withholding Treatment
/ statistics & numerical data
Young Adult
allogeneic hematopoietic stem cell transplantation (allo-HCT)
blinatumomab
inotuzumab ozogamicin
relapsed/refractory (RR) acute lymphoblastic leukemia (ALL)
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
revised:
25
09
2020
received:
11
05
2020
accepted:
23
10
2020
pubmed:
2
12
2020
medline:
11
11
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity. In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared. Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety-two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09). Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.
Sections du résumé
BACKGROUND
The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity.
METHODS
In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared.
RESULTS
Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety-two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09).
CONCLUSIONS
Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.
Substances chimiques
Antibodies, Bispecific
0
Antineoplastic Agents, Immunological
0
blinatumomab
4FR53SIF3A
Inotuzumab Ozogamicin
P93RUU11P7
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1039-1048Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM120007
Pays : United States
Informations de copyright
© 2020 American Cancer Society.
Références
National Cancer Institute. Cancer Stat Facts: Leukemia-Acute Lymphocytic Leukemia (ALL). Accessed March 29, 2020. https://seer.cancer.gov/statfacts/html/alyl.html
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.
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.
Kantarjian H, Stein A, Gokbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-847.
Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375:740-753.
Martinelli G, Dombret H, Chevallier O, et al. Complete molecular and hematologic response in adult patients with relapsed/refractory (R/R) Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia (ALL) following treatment with blinatumomab: results from a phase 2 single-arm, multicenter study (ALCANTARA). Blood. 2015;126:679.
Badar T, Advani AS, Liedtke M, et al. Clinical outcome with allogeneic hematopoietic stem cell transplantation after blinatumomab or inotuzumab ozogamicin in patients with B-cell acute lymphoblastic leukemia: real world experience. Biol Blood Marrow Transplant. 2020;26:S101-S102.
Badar T, Szabo A, Wadleigh M, et al. Real world outcomes of adult B-cell acute lymphocytic leukemia patients treated with inotuzumab ozogamicin. Clin Lymphoma Myeloma Leuk. 2020;20:556-560.e2.
Badar T, Szabo A, Advani AS, et al. Real world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab. Blood. 2019;134:3809.
Salhotra A, Yang D, Mokhtari S, et al. Outcomes of allogeneic hematopoietic cell transplantation after salvage therapy with blinatumomab in patients with relapsed/refractory acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2020;26:1084-1090.
Jabbour E, Ravandi F, Kebriaei P, et al. Salvage chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD for patients with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: a phase 2 clinical trial. JAMA Oncol. 2018;4:230-234.
Delea TE, Zhang X, Amdahl J, et al. Cost effectiveness of blinatumomab versus inotuzumab ozogamicin in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia in the United States. Pharmacoeconomics. 2019;37:1177-1193.
Proskorovsky I, Su Y, Fahrbach K, et al. Indirect treatment comparison of inotuzumab ozogamicin versus blinatumomab for relapsed or refractory acute lymphoblastic leukemia. Adv Ther. 2019;36:2147-2160.
Thomas DA, Kantarjian H, Smith TL, et al. Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy. Cancer. 1999;86:1216-1230.
Assi R, Kantarjian H, Short NJ, et al. Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome-positive leukemia. Clin Lymphoma Myeloma Leuk. 2017;17:897-901.
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.
Kantarjian H, Ravandi F, Short NJ, et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2018;19:240-248.