Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials.
T-cell
acute lymphoblastic leukemia
outcome
refractory
relapsed
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
revised:
21
07
2021
received:
09
06
2021
accepted:
01
08
2021
pubmed:
19
8
2021
medline:
13
10
2021
entrez:
18
8
2021
Statut:
ppublish
Résumé
Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9-8.6) months, with a 4-year OS probability of 18% (95% CI, 9%-27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109-3.362), 2.958 (1.640-5.334), and 2.976 (1.157-7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
529-538Subventions
Organisme : "La Caixa" Foundation and ISCIII
ID : PI19/01828
Organisme : Generalitat de Catalunya (GRC)
ID : 2017 SGR288
Informations de copyright
© 2021 John Wiley & Sons Ltd.
Références
Pocock R, Farah N, Richardson SE, Mansour MR. Current and emerging therapeutic approaches for T-cell acute lymphoblastic leukaemia. Br J Haematol. 2021;194:28-43. doi:10.1111/bjh.17310
Patel AA, Thomas J, Rojek AE, Stock W. Biology and treatment paradigms in T cell acute lymphoblastic leukemia in older adolescents and adults. Curr Treat Options Oncol. 2020;21(7):57.
Kim R, Boissel N, Touzart A, et al. Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation. Leukemia. 2020;34(7):1730-1740.
Bassan R, Pavoni C, Intermesoli T, et al. Updated risk-oriented strategy for acute lymphoblastic leukemia in adult patients 18-65 years: NILG ALL 10/07. Blood Cancer J. 2020;10(11):119. doi:10.1038/s41408-020-00383-2
Patel B, Kirkwood AA, Dey A, et al. Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial. Leukemia. 2017;31(1):58-64.
Marks DI, Paietta EM, Moorman AV, et al. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009;114(25):5136-5145.
Barba P, Morgades M, Montesinos P, et al. Increased survival due to lower toxicity for high-risk T-cell acute lymphoblastic leukemia patients in two consecutive pediatric-inspired PETHEMA trials. Eur J Haematol. 2019;102(1):79-86.
Abaza Y, Kantarjian M, Faderl S, et al. Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma. Am J Hematol. 2018;93(1):91-99.
Morita K, Jain N, Kantarjian H, et al. Outcome of T-cell acute lymphoblastic leukemia/lymphoma: focus on near-ETP phenotype and differential impact of nelarabine. Am J Hematol. 2021;96(5):589-598.
DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007;109(12):5136-5142.
Gökbuget N, Basara N, Baurmann H, et al. High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood. 2011;118(13):3504-3511.
Dunsmore KP, Winter SS, Devidas M, et al. A phase III randomized clinical trial testing nelarabine in newly diagnosed T-cell acute lymphoblastic leukemia. J Clin Oncol. 2020;38(28):3282-3293.
Richard-Carpentier G, Jabbour E, Short NJ, et al. Clinical experience with venetoclax combined with chemotherapy for relapsed or refractory T-cell acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2020;20(4):212-218.
Pullarkat VA, Lacayo NJ, Jabbour E, et al. Venetoclax and navitoclax in combination with chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. Cancer Discov. 2021;11:1440-1453. doi:10.1158/2159-8290.CD-20-1465
Litzow MR, Ferrando AA. How I treat T-cell acute lymphoblastic leukemia in adults. Blood. 2015;126(7):833-841.
McMahon CM, Luger SM. Relapsed T cell ALL: Current approaches and new directions. Curr Hematol Malig Rep. 2019;14(2):83-93.
Huguet F, Leguay T, Raffoux E, et al. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on adult acute lymphoblastic leukemia intergroup. Leuk Lymphoma. 2015;56(4):847-857.
Samra B, Alotaibi AS, Short NJ, et al. Outcome of adults with relapsed/refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Am J Hematol. 2020;95(9):E245-E247.
Gaynon PS, Harris RE, Altman AJ, et al. Bone marrow transplantation versus prolonged intensive chemotherapy for children with acute lymphoblastic leukemia and an initial bone marrow relapse within 12 months of the completion of primary therapy: Children’s Oncology Group study CCG-1941. J Clin Oncol. 2006;24(19):3150-3156.
Ko RH, Ji L, Barnette P, et al. Outcome of patients treated for relapsed or refractory acute lymphoblastic leukemia: a therapeutic advance in Childhood Leukemia Consortium study. J Clin Oncol. 2010;28(4):648-654.
Ribera JM, Oriol A, Morgades M, et al. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014;32(15):1595-1604.
Ribera JM, Morgades M, Ciudad J, et al. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia. Blood. 2021;137(14):1879-1894.
Sanchez-Martinez D, Baroni ML, Gutierrez-Aguera F, et al. Fratricide-resistant CD1a specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood. 2019;133(21):2291-2304.
Degryse S, Cools J. JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia. J Hematol Oncol. 2015;8:91.
Deenik W, Beverloo HB, Wattel MM, et al. Rapid complete cytogenetic remission after upfront dasatinib monotherapy in a patient with a NUP214-ABL1-positive T-cell acute lymphoblastic leukemia. Leukemia. 2009;23(3):627-629.