A Multicenter Phase II, Double-Blind, Placebo-Controlled Trial of Maintenance Ixazomib After Allogeneic Transplantation for High-Risk Multiple Myeloma: Results of the Blood and Marrow Transplant Clinical Trials Network 1302 Trial

被引:3
作者
Bashir, Qaiser [1 ]
Nishihori, Taiga [2 ]
Pasquini, Marcelo C. [3 ]
Martens, Michael J. [3 ]
Wu, Juan [4 ]
Alsina, Melissa [2 ]
Anasetti, Claudio [2 ]
Brunstein, Claudio [5 ]
Dawson, Peter [4 ]
Efebera, Yvonne [6 ,7 ]
Gasparetto, Cristina [8 ]
Geller, Nancy [9 ]
Giralt, Sergio [10 ]
Hall, Aric C. [11 ]
Koreth, John [12 ]
McCarthy, Philip [13 ]
Scott, Emma [14 ]
Stadtmauer, Edward A. [15 ]
Vesole, David H. [16 ]
Hari, Parameswaran [3 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX USA
[2] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplant & Cellular Immunot, Tampa, FL USA
[3] Med Coll Wisconsin, Dept Med, Milwaukee, WI USA
[4] Emmes Co, Biostat Dept, Rockville, MD USA
[5] Univ Minnesota, Dept Med, Minneapolis, MN USA
[6] Ohio State Univ, Biostat Dept, Columbus, OH USA
[7] Ohio Hlth Blood & Marrow Transplant, Columbus, OH USA
[8] Duke Univ, Dept Med, Durham, NC USA
[9] NHLBI, Off Biostat Res, NIH, Bethesda, MD USA
[10] Mem Sloan Kettering Canc Ctr, Div Hematol Malignancies, New York, NY USA
[11] Univ Wisconsin, Dept Med, Madison, WI USA
[12] Dana Farber Canc Inst, Stem Cell Transplantat, Boston, MA USA
[13] Roswell Park Comprehens Canc Ctr, Dept Med, Buffalo, NY USA
[14] Janssen Pharmaceut Co Johnson & Johnson, Clin Res Hematol Oncol, Horsham, PA USA
[15] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA USA
[16] Hackensack Meridian Sch Med, Myeloma Div, John Theurer Canc Ctr, Hackensack, NJ USA
来源
TRANSPLANTATION AND CELLULAR THERAPY | 2023年 / 29卷 / 06期
基金
美国国家卫生研究院;
关键词
Multiple myeloma; Allogeneic hematopoietic cell; transplantation; Ixazomib; Maintenance; STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; HOST-DISEASE PROPHYLAXIS; LENALIDOMIDE MAINTENANCE; CONSENSUS STATEMENT; RESPONSE CRITERIA; BORTEZOMIB; LEUKEMIA; I/II;
D O I
10.1016/j.jtct.2022.07.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The role of allogeneic hematopoietic cell transplantation (allo-HCT) followed by maintenance therapy in high-risk multiple myeloma (MM) remains controversial. We evaluated the efficacy of ixazomib maintenance therapy after reduced-intensity conditioning allo-HCT from HLA-matched donors in patients with high-risk MM. The primary study endpoint was progression-free survival (PFS) postrandomization, treated as a time to event. Secondary endpoints were grade II-IV and grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, best response, disease progression, nonrelapsemortality (NRM), overall survival (OS), toxicity, infection, and health-related quality of life. In this phase 2, double-blinded, prospective multicenter trial, we randomized patients with high-riskMM(ie, those with poor-risk cytogenetics, plasma cell leukemia, or relapsingwithin 24 months after autologous HCT) to ixazomib (3 mg on days 1, 8, and 15) or placebo after allo-HCT. The conditioning regimen included fludarabine/melphalan/bortezomib with tacrolimus plus methotrexate for GVHD. Fifty-seven patients were enrolled, of whom 52 (91.2%) underwent allo-HCT and 43 (82.7%) were randomized to ixazomib versus placebo. At 21 months postrandomization, the ixazomib and placebo groups had similar PFS (55.3% versus 59.1%; P = 1.00) and OS (94.7% versus 86.4%; P =.17). The cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% versus 0%) and chronic GVHD at 12 months (68.6% versus 63.6%) also were similar in the 2 groups. The secondary analysis showed that at 24 months post-allo-HCT, PFS and OSwere 52% and 82%, respectively, with a corresponding NRMof 11.7%. These results demonstrate the safety anddurable disease control with allo-HCT in high-riskMMpatients. We could not adequately assess the efficacy of ixazomib maintenance because the trial terminated early owing to enrollment delays, but there was no indication of any impact on outcomes. (c) 2023 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.
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收藏
页码:358e1 / 358e7
页数:7
相关论文
共 29 条
  • [11] Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors
    Koreth, John
    Stevenson, Kristen E.
    Kim, Haesook T.
    Garcia, Michael
    Ho, Vincent T.
    Armand, Philippe
    Cutler, Corey
    Ritz, Jerome
    Antin, Joseph H.
    Soiffer, Robert J.
    Alyea, Edwin P., III
    [J]. BLOOD, 2009, 114 (18) : 3956 - 3959
  • [12] Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial
    Krishnan, Amrita
    Pasquini, Marcelo C.
    Logan, Brent
    Stadtmauer, Edward A.
    Vesole, David H.
    Alyea, Edwin, III
    Antin, Joseph H.
    Comenzo, Raymond
    Goodman, Stacey
    Hari, Parameswaran
    Laport, Ginna
    Qazilbash, Muzaffar H.
    Rowley, Scott
    Sahebi, Firoozeh
    Somlo, George
    Vogl, Dan T.
    Weisdorf, Daniel
    Ewell, Marian
    Wu, Juan
    Geller, Nancy L.
    Horowitz, Mary M.
    Giralt, Sergio
    Maloney, David G.
    [J]. LANCET ONCOLOGY, 2011, 12 (13) : 1195 - 1203
  • [13] Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma
    Kröger, N
    Schwerdtfeger, R
    Kiehl, M
    Sayer, HG
    Renges, H
    Zabelina, T
    Fehse, B
    Tögel, F
    Wittkowsky, G
    Kuse, R
    Zander, AR
    [J]. BLOOD, 2002, 100 (03) : 755 - 760
  • [14] Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time
    Kumar, S. K.
    Dispenzieri, A.
    Fraser, R.
    Mingwei, F.
    Akpek, G.
    Cornell, R.
    Kharfan-Dabaja, M.
    Freytes, C.
    Hashmi, S.
    Hildebrandt, G.
    Holmberg, L.
    Kyle, R.
    Lazarus, H.
    Lee, C.
    Mikhael, J.
    Nishihori, T.
    Tay, J.
    Usmani, S.
    Vesole, D.
    Vij, R.
    Wirk, B.
    Krishnan, A.
    Gasparetto, C.
    Mark, T.
    Nieto, Y.
    Hari, P.
    D'Souza, A.
    [J]. LEUKEMIA, 2018, 32 (04) : 986 - 995
  • [15] International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma
    Kumar, Shaji
    Paiva, Bruno
    Anderson, Kenneth C.
    Durie, Brian
    Landgren, Ola
    Moreau, Philippe
    Munshi, Nikhil
    Lonial, Sagar
    Blade, Joan
    Mateos, Maria-Victoria
    Dimopoulos, Meletios
    Kastritis, Efstathios
    Boccadoro, Mario
    Orlowski, Robert
    Goldschmidt, Hartmut
    Spencer, Andrew
    Hou, Jian
    Chng, Wee Joo
    Usmani, Saad Z.
    Zamagni, Elena
    Shimizu, Kazuyuki
    Jagannath, Sundar
    Johnsen, Hans E.
    Terpos, Evangelos
    Reiman, Anthony
    Kyle, Robert A.
    Sonneveld, Pieter
    Richardson, Paul G.
    McCarthy, Philip
    Ludwig, Heinz
    Chen, Wenming
    Cavo, Michele
    Harousseau, Jean-Luc
    Lentzsch, Suzanne
    Hillengass, Jens
    Palumbo, Antonio
    Orfao, Alberto
    Rajkumar, S. Vincent
    Miguel, Jesus San
    Avet-Loiseau, Herve
    [J]. LANCET ONCOLOGY, 2016, 17 (08) : E328 - E346
  • [16] International Myeloma Working Group Consensus Statement Regarding the Current Status of Allogeneic Stem-Cell Transplantation for Multiple Myeloma
    Lokhorst, Henk
    Einsele, Hermann
    Vesole, David
    Bruno, Benedetto
    Miguel, Jesus San
    Perez-Simon, Jose A.
    Kroger, Nicolaus
    Moreau, Philippe
    Gahrton, Gosta
    Gasparetto, Cristina
    Giralt, Sergio
    Bensinger, William
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (29) : 4521 - 4530
  • [17] A Phase I/II Trial Combining High-Dose Melphalan and Autologous Transplant with Bortezomib for Multiple Myeloma: A Dose- and Schedule-Finding Study
    Lonial, Sagar
    Kaufman, Jonathan
    Tighiouart, Mourad
    Nooka, Ajay
    Langston, Amelia A.
    Heffner, Leonard T.
    Torre, Claire
    McMillan, Stephanie
    Renfroe, Heather
    Harvey, R. Donald
    Lechowicz, Mary J.
    Khoury, H. Jean
    Flowers, Christopher R.
    Waller, Edmund K.
    [J]. CLINICAL CANCER RESEARCH, 2010, 16 (20) : 5079 - 5086
  • [18] Allograft for Myeloma: examining Pieces of the Jigsaw Puzzle
    Malek, Ehsan
    El-Jurdi, Najla
    Kroeger, Nicolaus
    de Lima, Marcos
    [J]. FRONTIERS IN ONCOLOGY, 2017, 7
  • [19] Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis
    McCarthy, Philip L.
    Holstein, Sarah A.
    Petrucci, Maria Teresa
    Richardson, Paul G.
    Hulin, Cyrille
    Tosi, Patrizia
    Bringhen, Sara
    Musto, Pellegrino
    Anderson, Kenneth C.
    Caillot, Denis
    Gay, Francesca
    Moreau, Philippe
    Marit, Gerald
    Jung, Sin-Ho
    Yu, Zhinuan
    Winograd, Benjamin
    Knight, Robert D.
    Palumbo, Antonio
    Attal, Michel
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (29) : 3279 - +
  • [20] Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2
    Munshi, Nikhil C.
    Anderson, Kenneth C.
    Bergsagel, P. Leif
    Shaughnessy, John
    Palumbo, Antonio
    Durie, Brian
    Fonseca, Rafael
    Stewart, A. Keith
    Harousseau, Jean-Luc
    Dimopoulos, Meletios
    Jagannath, Sundar
    Hajek, Roman
    Sezer, Orhan
    Kyle, Robert
    Sonneveld, Pieter
    Cavo, Michele
    Rajkumar, S. Vincent
    San Miguel, Jesus
    Crowley, John
    Avet-Loiseau, Herve
    [J]. BLOOD, 2011, 117 (18) : 4696 - 4700