Phase 2 study of hyper-CMAD with liposomal vincristine for patients with newly diagnosed acute lymphoblastic leukemia.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Cytarabine
/ administration & dosage
Disease-Free Survival
Female
Follow-Up Studies
Humans
Liposomes
Male
Methotrexate
/ administration & dosage
Middle Aged
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Rituximab
/ administration & dosage
Survival Rate
Vincristine
/ administration & dosage
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
30
12
2019
revised:
04
03
2020
accepted:
10
03
2020
pubmed:
15
3
2020
medline:
18
8
2020
entrez:
15
3
2020
Statut:
ppublish
Résumé
Liposomal vincristine is designed to reduce neurotoxicity and increase dose intensity delivery, and has been approved as salvage therapy in relapsed/refractory acute lymphoblastic leukemia (ALL). Our aim was to evaluate the response rate, toxicities, and outcome of adults with newly diagnosed ALL who received liposomal vincristine, rather than regular vincristine in combination with intensive chemotherapy (Hyper-CMAD). In a single-center, phase 2 study, patients ≥18 years with newly-diagnosed B-cell ALL were eligible to receive hyper-CMAD alternating with high-dose methotrexate and cytarabine. Rituximab was administered in CD20 positive ALL. Tyrosine kinase inhibitors (imatinib or dasatinib) were added in Philadelphia chromosome-positive (Ph-positive) ALL. Thirty-one patients were enrolled, median follow-up of 59 months (0.3-70). Thirteen patients (42%) had CD20 positive ALL, and 21 (68%) had Ph-positive ALL. Thirty (97%) achieved complete remission (CR). All 26 patients with abnormal karyotype achieved complete cytogenetic response (CCyR), and 27/30 (90%) achieved negative minimal residual disease status by multicolor flow cytometry. Of 20 evaluable Ph-positive ALL patients, major molecular response (MMR) was achieved in 19 patients (95%); complete molecular response (CMR) in 14 (70%). Grade 3/4 peripheral neuropathy was observed in five (16%) with all grade peripheral neuropathy in 21 (68%). With a median follow-up of 59 months, 21 (68%) patients are alive. The 5-year CR duration and survival rates were 73% and 61%, respectively. Ten (32%) patients died: one, sepsis on C1D10; four, unknown; one, post-transplant complications; four, relapse. Hyper-CMAD with liposomal vincristine is safe and demonstrated high response and survival rates in newly diagnosed ALL.
Substances chimiques
Liposomes
0
Cytarabine
04079A1RDZ
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Methotrexate
YL5FZ2Y5U1
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
734-739Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
Kantarjian H, Thomas D, OʼBrien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788-2801.
Yan Z, Zhu ZL, Qian ZZ, et al. Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors. Acta Pharmacol Sin. 2012;33:852-858.
OʼBrien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013;31:676-683.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202497s000lbl.pdf. Accessed January 13, 2019.
Ravandi F, Jorgensen JL, OʼBrien SM, et al. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukemia. Br J Haematol. 2016;172:392-400.
Short NJ, Jabbour E, Albitar M, et al. Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of North American experts. Am J Hematol. 2019;94:257-265.
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.
Jabbour E, Kantarjian H, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-centre, phase 2 study. Lancet Oncol. 2015;16:1547-1555.
Short NJ, Jabbour E, Sasaki K, et al. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2016;128:504-507.
Thall PF, Simon R, Estey EH. Bayesian sequential monitoring designs for single-arm clinical trials with multiple outcomes. Stat Med. 1995;14:357-379.
Thall PF, Simon R, Estey EH. New statistical strategy for monitoring safety and efficacy in single-arm clinical trials. J Clin Oncol. 1996;14:296-303.
Thall PF, Sung H-G. Some extensions and applications of a Bayesian strategy for monitoring multiple outcomes in clinical trials. Stat Med. 1998;17:1563-1580.
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.
Kantarjian H, Stein A, Gokbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-847.
Jabbour E, Pui CH, Kantarjian H. Progress and innovations in the management of adult acute lymphoblastic leukemia. JAMA Oncol. 2018;4:1413-1420.
van Schie RM, Brüggemann RJM, Hoogerbrugge PM, te Loo DMWM. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukemia. J Antimicrob Chemother. 2011;66:1853-1856.