TY - JOUR
T1 - Clinical Outcomes in Patients with FLT3-ITD-Mutated Relapsed/Refractory Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation after Quizartinib or Salvage Chemotherapy in the QuANTUM-R Trial
AU - Ganguly, Siddhartha
AU - Cortes, Jorge E.
AU - Krämer, Alwin
AU - Levis, Mark J.
AU - Martinelli, Giovanni
AU - Perl, Alexander E.
AU - Russell, Nigel H.
AU - Arunachalam, Meena
AU - Santos, Cedric Dos
AU - Gammon, Guy
AU - Lesegretain, Arnaud
AU - Mires, Derek E.
AU - Pham, Hoang
AU - Wang, Yibin
AU - Khaled, Samer K.
N1 - Funding Information:
We thank the patients and their families; the QuANTUM-R investigators and their staff; the Daiichi Sankyo team, who contributed to the execution of this study, analysis, and interpretation of its results, including Li-An Xu, Flora Berisha, Aziz Benzhora; Ruth Namuyinga, Yufen Zhang, and former employees of Daiichi Sankyo; and Sergey Korkhov, Zhenyu Wang, and Tobias Guennel from Precision for Medicine. Jillian Brechbiel, PhD (SciMentum, a Nucleus Global company), provided medical writing support, which was funded by Daiichi Sankyo in accordance with Good Publication Practice guidelines. The results of this post hoc analysis from the QuANTUM-R trial were initially presented at the 61st American Society of Hematology Annual Meeting on December 9, 2019. Financial disclosure: This study was sponsored, funded, and supported by Daiichi Sankyo. Conflict of interest statement: S.G. has received personal fees from Seattle Genetics, Kite Pharmaceuticals, and Kadmon. J.E.C. has received grants and personal fees from Daiichi Sankyo, Novartis, Pfizer, Takeda, Biopath Holdings, and Jazz Pharmaceuticals and grants from Celgene, Merus, Amphivena Therapeutics, and Forma Therapeutics. A.K. has received travel support from Daiichi Sankyo and Roche, reimbursement to the University of Heidelberg, and grants from Bayer and Bristol Myers Squibb. M.J.L. received grants and personal fees from Astellas and Amgen, personal fees from Daiichi Sankyo, and Agios, and grants from Fujifilm. A.E.P. has received grants, personal fees, and travel support from Daiichi Sankyo, Astellas Pharma, and AbbVie; grants and personal fees from Actinium; nonfinancial support from Novartis; personal fees from Loxo Oncology, Syndax Pharmaceuticals, and Forma Therapeutics; and grants from Fujifilm and Bayer. G.M. and N.H.R. have nothing to disclose. M.A. C.D.S. A.L. D.E.M. H.P. and Y.W. are employees and shareholders of Daiichi Sankyo. G.G. has received personal fees from Daiichi Sankyo. S.K.K. has received personal fees and nonfinancial support from Daiichi Sankyo. Financial disclosure: See Acknowledgments on page XXX.
Funding Information:
We thank the patients and their families; the QuANTUM-R investigators and their staff; the Daiichi Sankyo team, who contributed to the execution of this study, analysis, and interpretation of its results, including Li-An Xu, Flora Berisha, Aziz Benzhora; Ruth Namuyinga, Yufen Zhang, and former employees of Daiichi Sankyo; and Sergey Korkhov, Zhenyu Wang, and Tobias Guennel from Precision for Medicine. Jillian Brechbiel, PhD (SciMentum, a Nucleus Global company), provided medical writing support, which was funded by Daiichi Sankyo in accordance with Good Publication Practice guidelines. The results of this post hoc analysis from the QuANTUM-R trial were initially presented at the 61st American Society of Hematology Annual Meeting on December 9, 2019.
Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy
PY - 2020
Y1 - 2020
N2 - Despite the substantial clinical activity of fms-related tyrosine kinase 3 (FLT3) inhibitors in relapsed or refractory (R/R) FLT3-ITD‒positive acute myelogenous leukemia (AML), durable remissions and prolonged survival in this population require allogeneic hematopoietic stem cell transplantation (allo-HSCT). Quizartinib, a once-daily oral, highly potent, and selective FLT3 inhibitor, significantly prolonged overall survival (OS) and improved clinical benefit compared with salvage chemotherapy (median OS, 6.2 months versus 4.7 months; hazard ratio [HR], .76; 95% confidence interval [CI], .58 to .98; P = .018; composite complete remission [CRc] rate, 48% versus 27%; median duration of CRc, 2.8 months versus 1.2 months; mortality rate, .8% versus 14% by day 30, 7% versus 24% by day 60) in patients with R/R FLT3-ITD AML in the phase 3 QuANTUM-R trial. In this post hoc analysis, we described the characteristics of and clinical outcomes in patients who underwent on-study HSCT in QuANTUM-R at the investigator's discretion and institutional practices. Of 367 randomized patients, 78 (32%) in the quizartinib arm and 14 (11%) in the salvage chemotherapy arm underwent on-study allo-HSCT without any intervening therapy for AML after quizartinib or study-specified salvage chemotherapy. Pooled data of patients from both treatment arms showed a longer median overall survival (OS) in transplant recipients versus those treated without allo-HSCT (12.2 months versus 4.4 months; HR, .315; 95% CI, .233 to .427). Pooled data also showed a longer median OS in patients with a last recorded response of CRc before allo-HSCT versus patients without a CRc (20.1 months versus 8.8 months; HR, .506; 95% CI, .296 to .864). By treatment arm, the median OS was 25.1 months with quizartinib and 20.1 months with salvage chemotherapy in patients with a last recorded response of CRc before allo-HSCT. Forty-eight patients in the quizartinib arm continued quizartinib treatment after allo-HSCT. In the 31 patients with a last recorded response of CRc before allo-HSCT who continued quizartinib after allo-HSCT, the median OS was 27.1 months. Continuation of quizartinib after allo-HSCT was tolerable, and no new safety signals were identified. These results suggest that post-transplantation survival following salvage chemotherapy and quizartinib treatment are similar. However, quizartinib response occurs more frequently than with salvage chemotherapy, potentially allowing more patients to undergo transplantation and achieve durable clinical benefit. In addition, post-transplant quizartinib was found to be tolerable and may be associated with prolonged survival in some patients, highlighting its potential value in the management of patients with FLT3-ITD R/R AML.
AB - Despite the substantial clinical activity of fms-related tyrosine kinase 3 (FLT3) inhibitors in relapsed or refractory (R/R) FLT3-ITD‒positive acute myelogenous leukemia (AML), durable remissions and prolonged survival in this population require allogeneic hematopoietic stem cell transplantation (allo-HSCT). Quizartinib, a once-daily oral, highly potent, and selective FLT3 inhibitor, significantly prolonged overall survival (OS) and improved clinical benefit compared with salvage chemotherapy (median OS, 6.2 months versus 4.7 months; hazard ratio [HR], .76; 95% confidence interval [CI], .58 to .98; P = .018; composite complete remission [CRc] rate, 48% versus 27%; median duration of CRc, 2.8 months versus 1.2 months; mortality rate, .8% versus 14% by day 30, 7% versus 24% by day 60) in patients with R/R FLT3-ITD AML in the phase 3 QuANTUM-R trial. In this post hoc analysis, we described the characteristics of and clinical outcomes in patients who underwent on-study HSCT in QuANTUM-R at the investigator's discretion and institutional practices. Of 367 randomized patients, 78 (32%) in the quizartinib arm and 14 (11%) in the salvage chemotherapy arm underwent on-study allo-HSCT without any intervening therapy for AML after quizartinib or study-specified salvage chemotherapy. Pooled data of patients from both treatment arms showed a longer median overall survival (OS) in transplant recipients versus those treated without allo-HSCT (12.2 months versus 4.4 months; HR, .315; 95% CI, .233 to .427). Pooled data also showed a longer median OS in patients with a last recorded response of CRc before allo-HSCT versus patients without a CRc (20.1 months versus 8.8 months; HR, .506; 95% CI, .296 to .864). By treatment arm, the median OS was 25.1 months with quizartinib and 20.1 months with salvage chemotherapy in patients with a last recorded response of CRc before allo-HSCT. Forty-eight patients in the quizartinib arm continued quizartinib treatment after allo-HSCT. In the 31 patients with a last recorded response of CRc before allo-HSCT who continued quizartinib after allo-HSCT, the median OS was 27.1 months. Continuation of quizartinib after allo-HSCT was tolerable, and no new safety signals were identified. These results suggest that post-transplantation survival following salvage chemotherapy and quizartinib treatment are similar. However, quizartinib response occurs more frequently than with salvage chemotherapy, potentially allowing more patients to undergo transplantation and achieve durable clinical benefit. In addition, post-transplant quizartinib was found to be tolerable and may be associated with prolonged survival in some patients, highlighting its potential value in the management of patients with FLT3-ITD R/R AML.
KW - Acute myelogenous leukemia
KW - Allogeneic hematopoietic stem cell transplantation
KW - FMS-related tyrosine kinase 3 internal tandem duplication
KW - Quizartinib
KW - Relapsed/refractory
UR - http://www.scopus.com/inward/record.url?scp=85095813915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095813915&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2020.09.036
DO - 10.1016/j.bbmt.2020.09.036
M3 - Article
C2 - 33017662
AN - SCOPUS:85095813915
SN - 1083-8791
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
ER -