Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy
The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients...
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| Published in | Leukemia Vol. 33; no. 9; pp. 2266 - 2275 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.09.2019
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T
0
) was 50.1 months. The median overall survival (OS) from T
0
for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T
0
in 249 (90%) patients. Overall response rate to first regimen after T
0
was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population. |
|---|---|
| AbstractList | The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T0) was 50.1 months. The median overall survival (OS) from T0 for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T0 in 249 (90%) patients. Overall response rate to first regimen after T0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population. The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T ) was 50.1 months. The median overall survival (OS) from T for the entire cohort was 8.6 [95% C.I. 7.5-9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for "penta-refractory" patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T in 249 (90%) patients. Overall response rate to first regimen after T was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population. The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T 0 ) was 50.1 months. The median overall survival (OS) from T 0 for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T 0 in 249 (90%) patients. Overall response rate to first regimen after T 0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population. |
| Author | Umyarova, Elvira Vij, Ravi Gandhi, Ujjawal H. Mansour, Joshua Kansagra, Ankit Hari, Parameswaran Paul, Barry McGehee, Elizabeth Kodali, Saranya Kang, Yubin Callander, Natalie S. Kumar, Shaji K. Scott, Emma C. Lakshman, Arjun Fiala, Mark A. Costa, Luciano J. Varnado, William Chhabra, Saurabh Narayana, Swapna Gupta, Ridhi Gahvari, Zhubin J. Neppalli, Amarendra Jagosky, Megan H. Usmani, Saad Z. Malek, Ehsan Barnstead, Alyssa Godby, Kelly N. Cornell, Robert F. Liedtke, Michaela |
| AuthorAffiliation | 1 Department of Medicine, Division of Hematology & Oncology, Vanderbilt University Medical Center, Nashville, TN 4 University of Texas Southwestern Medical Center, Dallas, TX 11 Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 13 Oregon Health & Science University, Portland, OR 5 Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute/Carolinas Health Care, Charlotte, NC 8 Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 7 Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL 12 Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC 9 Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 14 University of Vermont, College of Medicine, Burlington, VT 2 Division of Hematology, Mayo Clinic, Rochester, MN 10 Adult Hematologic Malignancies & Stem Cell |
| AuthorAffiliation_xml | – name: 9 Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI – name: 5 Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute/Carolinas Health Care, Charlotte, NC – name: 11 Hollings Cancer Center, Medical University of South Carolina, Charleston, SC – name: 4 University of Texas Southwestern Medical Center, Dallas, TX – name: 6 Stanford Cancer Institute, Stanford, CA – name: 1 Department of Medicine, Division of Hematology & Oncology, Vanderbilt University Medical Center, Nashville, TN – name: 14 University of Vermont, College of Medicine, Burlington, VT – name: 12 Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC – name: 10 Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH – name: 3 University of Wisconsin, Madison, WI – name: 8 Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO – name: 2 Division of Hematology, Mayo Clinic, Rochester, MN – name: 13 Oregon Health & Science University, Portland, OR – name: 7 Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL |
| Author_xml | – sequence: 1 givenname: Ujjawal H. surname: Gandhi fullname: Gandhi, Ujjawal H. organization: Department of Medicine, Division of Hematology & Oncology, Vanderbilt University Medical Center – sequence: 2 givenname: Robert F. surname: Cornell fullname: Cornell, Robert F. organization: Department of Medicine, Division of Hematology & Oncology, Vanderbilt University Medical Center – sequence: 3 givenname: Arjun surname: Lakshman fullname: Lakshman, Arjun organization: Division of Hematology, Mayo Clinic – sequence: 4 givenname: Zhubin J. surname: Gahvari fullname: Gahvari, Zhubin J. organization: University of Wisconsin – sequence: 5 givenname: Elizabeth surname: McGehee fullname: McGehee, Elizabeth organization: University of Texas Southwestern Medical Center – sequence: 6 givenname: Megan H. surname: Jagosky fullname: Jagosky, Megan H. organization: Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute/Carolinas Health Care – sequence: 7 givenname: Ridhi surname: Gupta fullname: Gupta, Ridhi organization: Stanford Cancer Institute – sequence: 8 givenname: William surname: Varnado fullname: Varnado, William organization: Division of Hematology/Oncology, University of Alabama at Birmingham – sequence: 9 givenname: Mark A. surname: Fiala fullname: Fiala, Mark A. organization: Department of Medicine, Division of Oncology, Washington University School of Medicine – sequence: 10 givenname: Saurabh surname: Chhabra fullname: Chhabra, Saurabh organization: Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin – sequence: 11 givenname: Ehsan surname: Malek fullname: Malek, Ehsan organization: Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center – sequence: 12 givenname: Joshua surname: Mansour fullname: Mansour, Joshua organization: Hollings Cancer Center, Medical University of South Carolina – sequence: 13 givenname: Barry surname: Paul fullname: Paul, Barry organization: Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine – sequence: 14 givenname: Alyssa surname: Barnstead fullname: Barnstead, Alyssa organization: Oregon Health & Science University – sequence: 15 givenname: Saranya surname: Kodali fullname: Kodali, Saranya organization: University of Vermont, College of Medicine – sequence: 16 givenname: Amarendra surname: Neppalli fullname: Neppalli, Amarendra organization: Hollings Cancer Center, Medical University of South Carolina – sequence: 17 givenname: Michaela surname: Liedtke fullname: Liedtke, Michaela organization: Stanford Cancer Institute – sequence: 18 givenname: Swapna surname: Narayana fullname: Narayana, Swapna organization: Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin – sequence: 19 givenname: Kelly N. surname: Godby fullname: Godby, Kelly N. organization: Division of Hematology/Oncology, University of Alabama at Birmingham – sequence: 20 givenname: Yubin surname: Kang fullname: Kang, Yubin organization: Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine – sequence: 21 givenname: Ankit orcidid: 0000-0001-6901-0782 surname: Kansagra fullname: Kansagra, Ankit organization: University of Texas Southwestern Medical Center – sequence: 22 givenname: Elvira surname: Umyarova fullname: Umyarova, Elvira organization: University of Vermont, College of Medicine – sequence: 23 givenname: Emma C. surname: Scott fullname: Scott, Emma C. organization: Oregon Health & Science University – sequence: 24 givenname: Parameswaran surname: Hari fullname: Hari, Parameswaran organization: Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin – sequence: 25 givenname: Ravi surname: Vij fullname: Vij, Ravi organization: Department of Medicine, Division of Oncology, Washington University School of Medicine – sequence: 26 givenname: Saad Z. surname: Usmani fullname: Usmani, Saad Z. organization: Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute/Carolinas Health Care – sequence: 27 givenname: Natalie S. surname: Callander fullname: Callander, Natalie S. organization: University of Wisconsin – sequence: 28 givenname: Shaji K. orcidid: 0000-0001-5392-9284 surname: Kumar fullname: Kumar, Shaji K. organization: Division of Hematology, Mayo Clinic – sequence: 29 givenname: Luciano J. orcidid: 0000-0001-5362-2469 surname: Costa fullname: Costa, Luciano J. email: ljcosta@uabmc.edu organization: Division of Hematology/Oncology, University of Alabama at Birmingham |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30858549$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | 692/308/153 692/699/67/1059/2325 692/699/67/1990/804 ADP-ribosyl Cyclase 1 - immunology Adult Aged Aged, 80 and over Alkylation Antibodies, Monoclonal - immunology Antibodies, Monoclonal, Humanized Antineoplastic Agents, Immunological - immunology Antineoplastic Combined Chemotherapy Protocols - immunology Cancer Research CD38 antigen Cohort Studies Critical Care Medicine Female Hematology Humans Immunologic Factors - immunology Immunomodulation Immunotherapy Immunotherapy - methods Intensive Internal Medicine Male Medical prognosis Medicine Medicine & Public Health Membrane Glycoproteins - immunology Middle Aged Monoclonal antibodies Multiple myeloma Multiple Myeloma - immunology Multiple Myeloma - therapy Oncology Progression-Free Survival Proteasome inhibitors Proteasome Inhibitors - immunology Survival Thermal resistance Young Adult |
| Title | Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy |
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