TY - JOUR
T1 - Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis
AU - Premkumar, Vikram J.
AU - Lentzsch, Suzanne
AU - Pan, Samuel
AU - Bhutani, Divaya
AU - Richter, Joshua
AU - Jagannath, Sundar
AU - Liedtke, Michaela
AU - Jaccard, Arnaud
AU - Wechalekar, Ashutosh D.
AU - Comenzo, Raymond
AU - Sanchorawala, Vaishali
AU - Royer, Bruno
AU - Rosenzweig, Michael
AU - Valent, Jason
AU - Schönland, Stefan
AU - Fonseca, Rafael
AU - Wong, Sandy
AU - Kapoor, Prashant
N1 - Funding Information:
V.J.P. has no conflicts of interest. S.L. is a shareholder of Caelum Biosciences and has received consultant fees from Caelum Biosciences, Bayer, AbbVie, Janssen, Proclara, and Takeda and receives research funding from Karyopharm and Sanofi. D.B. serves on the advisory board for Sanofi. M.L. receives honoraria from Amgen/Onyx, Pfizer, and Prothena; research funding from Amgen/Onyx, BlueBirdBio, Takeda, Pfizer, Celgene, Prothena, Genentech/Roche, Gilead, Janssen, Agios, and Celator; serves on an entity’s board of directors or advisory committee for Takeda, Pfizer, Caelum, Prothena, and Gilead; serves as a consultant for Amgen/Onyx committees, Genentech/Roche, Adaptive, and IQVIA/Jazz Pharmaceuticals. JR serves on the speaker’s bureau for Celgene and Janssen. J.R. serves in an advisory/consulting role for Celgene, Janssen Sanofi, Karyopharm, Antengene, X4 pharmaceuticals, Secura Bio, Adaptive biotechnologies, oncopeptides, and BMS. S.J. reports conflicts of interest with AbbVie, Bristol–Myers Squibb, Celgene, Janssen, Karyopharm, and Merck. A.J. served in a consulting or advisory role for Janssen, received research funding from Janssen and Celgene, and received honoraria from and had travel, accommodations, or other expenses paid or reimbursed by Abbvie, Janssen, and Celgene. R.C. received consulting fees/honoraria from Prothena, Janssen, Amgen, Takeda, Sanofi-Aventis, Unum, Caelum. R.C. received grant/research support from Prothena, Janssen, Takeda, and Karyopharm. M.R. is on the speakers' bureau for Celgene, Takeda, and Janssen. BR received consulting/fees from Janssen, Amgen, and Takeda. V.S. received research support from Celgene, Takeda, Prothena, Janssen; serves on advisory board for Proclara, Caleum, Abbvie. S.S. received research support from Janssen and Sanofi; serves on the advisory boards for Janssen and Prothena and received honoraria from Janssen, Takeda, and Prothena. J.V. has no conflicts of interest to disclose. A.W. has no conflicts of interest to disclose. E.K. received honoraria from Genesis Pharma, Takeda, Janssen, and Amgen. R.F. serves as a consultant for Amgen, BMS, Celgene, Takeda, Bayer, Janssen, Novartis, Pharmacyclics, Sanofi, Merck, Juno, Kite, Aduro, OncoTracker, GSK, and AbbVie. R.F. serves on the Scientific Advisory Board of Adaptive Biotechnologies and OncoTracker. S.W. served as a consultant for Amgen. P.K. is a principal investigator on studies for which Mayo Clinic received clinical research support from Takeda Pharmaceuticals., Amgen, Inc., AbbVie, GlaxoSmithKline, Janssen, and Sanofi. P.K. has served on the scientific advisory board or as a consultant or expert witness for Sanofi-aventis U.S., GlaxoSmithKline, Takeda Pharmaceuticals North America, Inc. with compensation to Mayo Clinic. P.K. has received personal compensation from Pharmacyclics, Cellectar, and Karyopharm for serving on the scientific advisory
Funding Information:
Funding/support: Dr. Premkumar was funded by a Conquer Cancer Foundation of ASCO Young Investigator Award and a T32 Training Award (T32CA203703). Funding for Dr. Premkumar provided salary support during work on this study. Dr. Lentzsch was funded by the Emerson Collective Cancer Research Fund, Cancer Research Institute, the Wade F.B. Thompson/Cancer Research Institute CLIP Grant, and the Herbert Irving Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (NCI P30 CA013696). Funding for Dr. Lentzsch provided salary support during work on this study. Role of funder/sponsor: The Conquer Cancer Foundation, the National Institutes of Health, the Emerson Collective Cancer Research Fund, Cancer Research Institute, the Wade F.B. Thompson/Cancer Research Institute, and the National Cancer Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the paper; and decision to submit the paper for publication.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/1
Y1 - 2021/1
N2 - Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02–0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04–0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
AB - Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02–0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04–0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
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U2 - 10.1038/s41408-020-00397-w
DO - 10.1038/s41408-020-00397-w
M3 - Article
C2 - 33431806
AN - SCOPUS:85099232841
SN - 2044-5385
VL - 11
JO - Blood cancer journal
JF - Blood cancer journal
IS - 1
M1 - 10
ER -