TY - JOUR
T1 - Romidepsin and lenalidomide-based regimens have efficacy in relapsed/refractory lymphoma
T2 - Combined analysis of two phase I studies with expansion cohorts
AU - Mehta-Shah, Neha
AU - Lunning, Matthew A.
AU - Moskowitz, Alison J.
AU - Boruchov, Adam M.
AU - Ruan, Jia
AU - Lynch, Peggy
AU - Hamlin, Paul A.
AU - Leonard, John
AU - Matasar, Matthew J.
AU - Myskowski, Patricia L.
AU - Marzouk, Evan
AU - Nair, Sumithra
AU - Sholklapper, Tamir
AU - Minnal, Veena
AU - Palomba, Maria L.
AU - Vredenburgh, James
AU - Kumar, Anita
AU - Noy, Ariela
AU - Straus, David J.
AU - Zelenetz, Andrew D.
AU - Schoder, Heiko
AU - Rademaker, Jurgen
AU - Schaffer, Wendy
AU - Galasso, Natasha
AU - Ganesan, Nivetha
AU - Horwitz, Steven M.
N1 - Funding Information:
N.M.S. has institutional research funding from Celgene/Bristol‐Myers Squibb, Genentech/Roche, Verastem Pharmaceuticals, Innate Pharmaceuticals, Corvus Pharmaceuticals. N.M.S. has served as a consultant for Kyowa Hakka Kirin, C4 Therapeutics, and Karyopharm. A.K. has research funding from Adaptive Biotechnologies, Abbvie Pharmaceuticals, Celgene, Pharmacyclics, Seattle Genetics, and Astra Zeneca. A.K. has also served as a consultant for Celgene, KiTE Pharmaceuticals, and has served on an advisory board for Astra Zeneca. A.N. has research funding from Pharmacyclics Rafael Pharma. A.N. has served on an advisory board for Jansen, Morphosys and has served as a consultant for Pharmacyclics. A.M. has received research support from ADC Therapeutics, Miragen, Seattle Genetics, Merck, Bristol‐Myers Squibb, and Incyte; and honoraria from Imbrium Therapeutics L.P., Janpix Ltd., Merck, Purdue Pharma L.C., and Seattle Genetics. J.P.L. has served as a consultant for Sutro, Miltenyi, AstraZeneca, Epizyme, BMS/Celgene, Regeneron, Bayer, Gilead/Kite, Karyopharm, GenMab, Genentech/Roche, Abbvie, and Incyte. J.R. has received research support and has served as a consultant with Celgene/BMS. M.L.P. has received personal or consulting fees from Novartis, Merck, Pharmacyclics and KiTE Pharmaceuticals. S.H. has consulted, received honorarium from, or participated in advisory boards for; ADC Therapeutics, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, Seattle Genetics, Takeda,Trillium Therapeutics, Verastem, and Vividion Therapeutics. S.H. has also received research support for clinical trials from ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Portola Pharmaceuticals, Seattle Genetics, Trillium Therapeutics, and Verastem. P.L., P.M., E.M., S.N., T.S., V.M., D.J.S., H.S., J.R., W.S., N.G. and N.G. have no relevant conflicts of interest to disclose.
Funding Information:
This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Amgen. This study was also supported by Celgene and NIH/NCI Cancer Center Support Grant P30 CA008748. NMS was supported by an American Society of Hematology Research Training Award for Fellows. NMS .s also supported by the Lymphoma Research Foundation (CDA number 610181).
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Romidepsin (histone deacetylase inhibitor), lenalidomide (immunomodulatory agent), and carfilzomib (proteasome inhibitor), have efficacy and lack cumulative toxicity in relapsed/refractory lymphoma. We performed two investigator initiated sequential phase I studies to evaluate the maximum tolerated dose (MTD) of romidepsin and lenalidomide (regimen A) and romidepsin, lenalidomide, and carfilzomib (regimen B) in relapsed/refractory lymphoma. Cohorts in T-cell lymphoma (TCL), B-cell lymphoma (BCL) were enrolled at the MTD. Forty-nine patients were treated in study A (27 TCL, 17 BCL, 5 Hodgkin lymphoma (HL)) and 27 (16 TCL, 11 BCL) in study B. The MTD of regimen A was romidepsin 14 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg oral on days 1–21 of a 28-day cycle. The MTD of regimen B was romidepsin 8 mg/m2 on days 1 and 8, lenalidomide 10 mg oral on days 1–14 and carfilzomib 36 mg/m2 IV on days 1 and 8 of a 21-day cycle. In study A, 94% had AEs ≥Grade 3, most commonly neutropenia (49%), thrombocytopenia (53%), and electrolyte abnormalities (49%). In study B 59% had AEs ≥Grade 3, including thrombocytopenia (30%) and neutropenia (26%). In study A the ORR was 49% (50% TCL, 47% BCL, 50% HL). In study B the ORR was 48% (50% TCL, 50% BCL). For study A and B the median progression free survival (PFS) was 5.7 months and 3.4 months respectively with 11 patients proceeding to allogeneic transplant. The combinations of romidepsin and lenalidomide and of romidepsin, lenalidomide and carfilzomib showed activity in relapsed/refractory lymphoma with an acceptable safety profile.
AB - Romidepsin (histone deacetylase inhibitor), lenalidomide (immunomodulatory agent), and carfilzomib (proteasome inhibitor), have efficacy and lack cumulative toxicity in relapsed/refractory lymphoma. We performed two investigator initiated sequential phase I studies to evaluate the maximum tolerated dose (MTD) of romidepsin and lenalidomide (regimen A) and romidepsin, lenalidomide, and carfilzomib (regimen B) in relapsed/refractory lymphoma. Cohorts in T-cell lymphoma (TCL), B-cell lymphoma (BCL) were enrolled at the MTD. Forty-nine patients were treated in study A (27 TCL, 17 BCL, 5 Hodgkin lymphoma (HL)) and 27 (16 TCL, 11 BCL) in study B. The MTD of regimen A was romidepsin 14 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg oral on days 1–21 of a 28-day cycle. The MTD of regimen B was romidepsin 8 mg/m2 on days 1 and 8, lenalidomide 10 mg oral on days 1–14 and carfilzomib 36 mg/m2 IV on days 1 and 8 of a 21-day cycle. In study A, 94% had AEs ≥Grade 3, most commonly neutropenia (49%), thrombocytopenia (53%), and electrolyte abnormalities (49%). In study B 59% had AEs ≥Grade 3, including thrombocytopenia (30%) and neutropenia (26%). In study A the ORR was 49% (50% TCL, 47% BCL, 50% HL). In study B the ORR was 48% (50% TCL, 50% BCL). For study A and B the median progression free survival (PFS) was 5.7 months and 3.4 months respectively with 11 patients proceeding to allogeneic transplant. The combinations of romidepsin and lenalidomide and of romidepsin, lenalidomide and carfilzomib showed activity in relapsed/refractory lymphoma with an acceptable safety profile.
UR - http://www.scopus.com/inward/record.url?scp=85111549617&partnerID=8YFLogxK
U2 - 10.1002/ajh.26288
DO - 10.1002/ajh.26288
M3 - Article
C2 - 34251048
AN - SCOPUS:85111549617
SN - 0361-8609
VL - 96
SP - 1211
EP - 1222
JO - American journal of hematology
JF - American journal of hematology
IS - 10
ER -