TY - JOUR
T1 - Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas
AU - Fanale, Michelle A.
AU - Horwitz, Steven M.
AU - Forero-Torres, Andres
AU - Bartlett, Nancy L.
AU - Advani, Ranjana H.
AU - Pro, Barbara
AU - Chen, Robert W.
AU - Davies, Andrew
AU - Illidge, Tim
AU - Uttarwar, Mayur
AU - Lee, Shih Yuan
AU - Ren, Hong
AU - Kennedy, Dana A.
AU - Shustov, Andrei R.
N1 - Funding Information:
This research was funded by Seattle Genetics, Inc., through the joint financial support of Seattle Genetics, Inc., and Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Limited. This work also was supported at Memorial Sloan-Kettering Cancer Center by a core facility grant from the National Institutes of Health National Cancer Institute (P30 CA008748).
Funding Information:
Conflict-of-interest disclosure: H.R., D.A.K. (at the time the work was done), and M.U. (at the time the work was done) are employees of and have equity ownership in Seattle Genetics, Inc. S.Y.-L. is an employee of and has equity ownership in Takeda Pharmaceuticals Limited. M.A.F. received research funding from Bristol-Myers Squibb, Merck & Co, Seattle Genetics, and Takeda; served on an advisory board for Seattle Genetics; received honoraria from Bristol-Myers Squibb, Merck & Co, Seattle Genetics, Takeda; served as a consultant for Bristol-Myers Squibb, Merck & Co, Seattle Genetics; and received travel expenses from Bristol-Myers Squibb, Merck & Co, Seattle Genetics, and Takeda. S.M.H. received research funding from ADCT Therapeutics, Aileron Therapeutics, Celgene, Forty Seven, Infinity/Verastem, Kyowa-Hakka-Kirin, Millennium/Takeda, Seattle Genetics, and Spectrum Pharmaceuticals and served as a consultant for Bristol-Myers Squibb, Celgene, Forty Seven, Infinity/Verastem, Kyowa-Hakka-Kirin, Millenium/Takeda, Mun-dipharma, and Seattle Genetics. A.F.-T. received research funding from and served on a speakers bureau for Seattle Genetics. N.L.B. received research funding from Affimed, Astra Zeneca, Bristol-Myers Squibb, Celgene, Forty Seven, Genentech, Gilead, ImaginAB, Immune Design, Janssen, KITE, Merck & Co, Millennium, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics and served on advisory boards for KITE, Pfizer, and Seattle Genetics. R.H.A. received research funding from Agensys, Bristol-Myers Squibb, Celgene, Forty Seven, Inc., Genentech/Roche, Infinity, Janssen Pharmaceutical, Kura, Merck, Millennium, Pharmacyclics, Regeneron, Seattle Genetics, and Teva Pharmaceuticals and served as a consultant for Astra Zeneca, Autolus, Bayer Healthcare Pharmaceuticals, Cell Medica, Seattle Genetics. B.P. received research funding from, served as a consultant for Seattle Genetics, and received honoraria and travel expenses from Seattle Genetics and Takeda Pharmaceuticals. R.W.C. received research funding from Bristol-Myers Squibb, Pharmacyclics, and Seattle Genetics; served as a consultant for Bristol-Myers Squibb, Genentech, Merck & Co, Pfizer, Pharmacyclics, and Seattle Genetics; and served on a speakers bureau for Genentech, Merck, and Seattle Genetics. A.D. received research funding from Acerta, Bayer, Celgene, Gilead, GSK, Janssen, Karyopharma, Pfizer, Roche, and Takeda; served on advisory boards for Celgene, CTI, Gilead, Karyopharma, Mundipharma, Roche, and Takeda; received honoraria from Celgene, CTI, Gilead, Janssen, Mundipharma, Pfizer, Roche, and Takeda; received travel expenses from CTI and Mundipharma and Takeda; and served as associate clinical director for the Southampton Clinical Trials Unit. T.I. received research funding from Seattle Genetics and honoraria from Takeda. D.A.K. has a patent (without royalties) with Seattle Genetics. A.R.S. received research funding from Actelion, Aileron, Bristol-Myers Squibb, Kyowa, Millennium/Takeda, Novartis, Pfizer, Seattle Genetics, and SPECTRUM and served as a consultant for SPECTRUM.
Publisher Copyright:
© 2018 by The American Society of Hematology
PY - 2018/5/10
Y1 - 2018/5/10
N2 - This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV1CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD301 peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.81 to 66.01 months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV1CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.
AB - This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV1CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD301 peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.81 to 66.01 months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV1CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.
UR - http://www.scopus.com/inward/record.url?scp=85047870943&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-12-821009
DO - 10.1182/blood-2017-12-821009
M3 - Article
C2 - 29507077
AN - SCOPUS:85047870943
VL - 131
SP - 2120
EP - 2124
JO - Blood
JF - Blood
SN - 0006-4971
IS - 19
ER -