Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma
Sarah A. Holstein, Vera J. Suman, Kouros Owzar, Katelyn Santo, Don M. Benson, Thomas C. Shea, Thomas Martin, Margarida Silverman, Luis Isola, Ravi Vij, Bruce D. Cheson, Charles Linker, Kenneth C. Anderson, Paul G. Richardson, Philip L. McCarthy
Oncology/Hematology
Oncology, Nebraska Medicine
James O Armitage Center for Hematological Malignancies Research
Great Plains IDeA-CTR
Center for Molecular Target Discovery & Development
CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.
Biology of Blood and Marrow Transplantation
https://doi.org/10.1016/j.bbmt.2020.03.028
Reduced-intensity conditioning
10.1016/j.bbmt.2020.03.028
Fingerprint Dive into the research topics of 'Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma'. Together they form a unique fingerprint.
Multiple Myeloma Medicine & Life Sciences
Allografts Medicine & Life Sciences
Stem Cells Medicine & Life Sciences
Allogeneic Cells Medicine & Life Sciences
Graft vs Host Disease Medicine & Life Sciences
fludarabine Medicine & Life Sciences
Cyclophosphamide Medicine & Life Sciences
Holstein, S. A., Suman, V. J., Owzar, K., Santo, K., Benson, D. M., Shea, T. C., Martin, T., Silverman, M., Isola, L., Vij, R., Cheson, B. D., Linker, C., Anderson, K. C., Richardson, P. G., & McCarthy, P. L. (2020). Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma. Biology of Blood and Marrow Transplantation, 26(8), 1414-1424. https://doi.org/10.1016/j.bbmt.2020.03.028
Long-Term Follow-up of CALGB (Alliance) 100001 : Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma. / Holstein, Sarah A.; Suman, Vera J.; Owzar, Kouros; Santo, Katelyn; Benson, Don M.; Shea, Thomas C.; Martin, Thomas; Silverman, Margarida; Isola, Luis; Vij, Ravi; Cheson, Bruce D.; Linker, Charles; Anderson, Kenneth C.; Richardson, Paul G.; McCarthy, Philip L.
In: Biology of Blood and Marrow Transplantation, Vol. 26, No. 8, 08.2020, p. 1414-1424.
Holstein, SA, Suman, VJ, Owzar, K, Santo, K, Benson, DM, Shea, TC, Martin, T, Silverman, M, Isola, L, Vij, R, Cheson, BD, Linker, C, Anderson, KC, Richardson, PG & McCarthy, PL 2020, 'Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma', Biology of Blood and Marrow Transplantation, vol. 26, no. 8, pp. 1414-1424. https://doi.org/10.1016/j.bbmt.2020.03.028
Holstein SA, Suman VJ, Owzar K, Santo K, Benson DM, Shea TC et al. Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma. Biology of Blood and Marrow Transplantation. 2020 Aug;26(8):1414-1424. https://doi.org/10.1016/j.bbmt.2020.03.028
Holstein, Sarah A. ; Suman, Vera J. ; Owzar, Kouros ; Santo, Katelyn ; Benson, Don M. ; Shea, Thomas C. ; Martin, Thomas ; Silverman, Margarida ; Isola, Luis ; Vij, Ravi ; Cheson, Bruce D. ; Linker, Charles ; Anderson, Kenneth C. ; Richardson, Paul G. ; McCarthy, Philip L. / Long-Term Follow-up of CALGB (Alliance) 100001 : Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma. In: Biology of Blood and Marrow Transplantation. 2020 ; Vol. 26, No. 8. pp. 1414-1424.
@article{1454c110293a4619ac7842764039f629,
title = "Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma",
abstract = "CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.",
keywords = "Allogeneic stem cell transplant, Autologous stem cell transplant, Multiple myeloma, Reduced-intensity conditioning",
author = "Holstein, {Sarah A.} and Suman, {Vera J.} and Kouros Owzar and Katelyn Santo and Benson, {Don M.} and Shea, {Thomas C.} and Thomas Martin and Margarida Silverman and Luis Isola and Ravi Vij and Cheson, {Bruce D.} and Charles Linker and Anderson, {Kenneth C.} and Richardson, {Paul G.} and McCarthy, {Philip L.}",
note = "Funding Information: Financial disclosure: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233180, UG1CA233191, UG1CA233331, UG1CA233339, UG1CA233373, and UG1CA239758. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Conflict of interest statement: S.A.H. has served on advisory boards for Adaptive Biotechnologies, Celgene, Genentech, Oncopeptides, and Takeda; has served as a consultant for GSK, Celgene, and Sorrento; has received research funding from Oncopeptides. T.M. has served as a consultant for Roche, GSK, and Legend and has received institutional research support from Sanofi, Amgen, Janssen, and Seattle Genetics. R.V. has received research funding from Bristol-Myers Squibb, Celgene, and Takeda and has served on advisory boards/received honoraria from Janssen, Bristol-Myers Squibb, Celgene, Karyopharm, Sanofi, Genentech, and Secura Bio. K.C.A. has served as an advisory board member for Celgene, BMS, Millennium Takeda, Sanofi, Janssen, and Gilead and is the founder of Oncopep and C4 Therapeutics. P.G.R. has received research support from Oncopeptides, Celgene, Takeda, and BMS and has served as an advisory committee member for Karyopharm, Oncopeptides, Celgene, Takeda, Janssen, and Sanofi. P.L.M. has received honoraria from Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, and Binding Site; research funding from Celgene; and has served on advisory committees/review panels/board membership for Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, Binding Site, and Karyopharm. The rest of the authors have no conflicts of interest to report. ",
doi = "10.1016/j.bbmt.2020.03.028",
journal = "Biology of Blood and Marrow Transplantation",
T1 - Long-Term Follow-up of CALGB (Alliance) 100001
T2 - Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma
AU - Holstein, Sarah A.
AU - Suman, Vera J.
AU - Owzar, Kouros
AU - Santo, Katelyn
AU - Benson, Don M.
AU - Shea, Thomas C.
AU - Martin, Thomas
AU - Silverman, Margarida
AU - Isola, Luis
AU - Vij, Ravi
AU - Cheson, Bruce D.
AU - Linker, Charles
AU - Anderson, Kenneth C.
AU - Richardson, Paul G.
AU - McCarthy, Philip L.
N1 - Funding Information: Financial disclosure: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233180, UG1CA233191, UG1CA233331, UG1CA233339, UG1CA233373, and UG1CA239758. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Conflict of interest statement: S.A.H. has served on advisory boards for Adaptive Biotechnologies, Celgene, Genentech, Oncopeptides, and Takeda; has served as a consultant for GSK, Celgene, and Sorrento; has received research funding from Oncopeptides. T.M. has served as a consultant for Roche, GSK, and Legend and has received institutional research support from Sanofi, Amgen, Janssen, and Seattle Genetics. R.V. has received research funding from Bristol-Myers Squibb, Celgene, and Takeda and has served on advisory boards/received honoraria from Janssen, Bristol-Myers Squibb, Celgene, Karyopharm, Sanofi, Genentech, and Secura Bio. K.C.A. has served as an advisory board member for Celgene, BMS, Millennium Takeda, Sanofi, Janssen, and Gilead and is the founder of Oncopep and C4 Therapeutics. P.G.R. has received research support from Oncopeptides, Celgene, Takeda, and BMS and has served as an advisory committee member for Karyopharm, Oncopeptides, Celgene, Takeda, Janssen, and Sanofi. P.L.M. has received honoraria from Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, and Binding Site; research funding from Celgene; and has served on advisory committees/review panels/board membership for Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, Binding Site, and Karyopharm. The rest of the authors have no conflicts of interest to report.
N2 - CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.
AB - CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.
KW - Allogeneic stem cell transplant
KW - Autologous stem cell transplant
KW - Multiple myeloma
KW - Reduced-intensity conditioning
U2 - 10.1016/j.bbmt.2020.03.028
DO - 10.1016/j.bbmt.2020.03.028
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation