Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies

Gary J Schiller¹, Brea C Lipe², Nizar J Bahlis³, Sascha A Tuchman⁴, William I Bensinger⁵, Heather J Sutherland⁶, Suzanne Lentzsch⁷, Muhamed Baljevic⁸, Darrell White⁹, Rami Kotb¹⁰, Christine I Chen¹¹, Adriana Rossi¹², Noa Biran¹³, Richard LeBlanc¹⁴, Sebastian Grosicki¹⁵, Maurizio Martelli¹⁶, Eberhard Gunsilius¹⁷, Ivan Špička¹⁸, Don Ambrose Stevens¹⁹, Thierry Facon²⁰, Mercedes Gironella Mesa²¹, Chris Zhang²², Dane R Van Domelen²², Ohad S Bentur²², Cristina Gasparetto²³

Affiliations

¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. Electronic address: gschiller@mednet.ucla.edu.
² University of Rochester, Rochester, NY.
³ Charbonneau Cancer Research Institute, Calgary, AB, Canada; Clinical Research Unit, Tom Baker Cancer Center, Calgary, AB, Canada.
⁴ University of North Carolina, Chapel Hill, NC.
⁵ Swedish Cancer Institute, Seattle, WA.
⁶ Vancouver General Hospital, Vancouver, BC, Canada.
⁷ Multiple Myeloma and Amyloidosis Service, Columbia University, New York, NY.
⁸ Vanderbilt University Medical Center, Nashville, TN.
⁹ Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada.
¹⁰ CancerCare Manitoba, Winnipeg, MB, Canada.
¹¹ Princess Margaret Cancer Centre, Toronto, ON, Canada.
¹² Weill Cornell Medicine, New York, NY.
¹³ Hackensack Meridian Health, Hackensack University Medical Center, Hackensack, NJ.
¹⁴ Maisonneuve-Rosemont Hospital, University of Montreal, QC, Canada.
¹⁵ Department of Hematology and Cancer Prevention, Medical University of Silesia, Katowice, Poland.
¹⁶ Department of Cellular Biotechnology and Hematology, Hematology Center, Umberto I Polyclinic of Rome, Rome, Italy.
¹⁷ Department of Internal Medicine V, Medical University Innsbruck, Innsbruck, Austria.
¹⁸ First Department of Medicine - Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic.
¹⁹ Norton Cancer Institute, St. Matthews Campus, Louisville, KY.
²⁰ Department of Hematology (Maladies du sang), Hôpital Huriez, CHU, Lille, France.
²¹ Department of Hematology, Vall d'Hebron University Hospital, Barcelona, Spain.
²² Karyopharm Therapeutics Inc., Newton, MA.
²³ Duke University Cancer Center, Durham, NC.

PMID: 37393120
DOI: 10.1016/j.clml.2023.06.001

Free article

Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies

Gary J Schiller et al. Clin Lymphoma Myeloma Leuk. 2023 Sep.

Free article

. 2023 Sep;23(9):e286-e296.e4.

doi: 10.1016/j.clml.2023.06.001. Epub 2023 Jun 5.

Authors

Affiliations

¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA. Electronic address: gschiller@mednet.ucla.edu.
² University of Rochester, Rochester, NY.
³ Charbonneau Cancer Research Institute, Calgary, AB, Canada; Clinical Research Unit, Tom Baker Cancer Center, Calgary, AB, Canada.
⁴ University of North Carolina, Chapel Hill, NC.
⁵ Swedish Cancer Institute, Seattle, WA.
⁶ Vancouver General Hospital, Vancouver, BC, Canada.
⁷ Multiple Myeloma and Amyloidosis Service, Columbia University, New York, NY.
⁸ Vanderbilt University Medical Center, Nashville, TN.
⁹ Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada.
¹⁰ CancerCare Manitoba, Winnipeg, MB, Canada.
¹¹ Princess Margaret Cancer Centre, Toronto, ON, Canada.
¹² Weill Cornell Medicine, New York, NY.
¹³ Hackensack Meridian Health, Hackensack University Medical Center, Hackensack, NJ.
¹⁴ Maisonneuve-Rosemont Hospital, University of Montreal, QC, Canada.
¹⁵ Department of Hematology and Cancer Prevention, Medical University of Silesia, Katowice, Poland.
¹⁶ Department of Cellular Biotechnology and Hematology, Hematology Center, Umberto I Polyclinic of Rome, Rome, Italy.
¹⁷ Department of Internal Medicine V, Medical University Innsbruck, Innsbruck, Austria.
¹⁸ First Department of Medicine - Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic.
¹⁹ Norton Cancer Institute, St. Matthews Campus, Louisville, KY.
²⁰ Department of Hematology (Maladies du sang), Hôpital Huriez, CHU, Lille, France.
²¹ Department of Hematology, Vall d'Hebron University Hospital, Barcelona, Spain.
²² Karyopharm Therapeutics Inc., Newton, MA.
²³ Duke University Cancer Center, Durham, NC.

PMID: 37393120
DOI: 10.1016/j.clml.2023.06.001

Abstract

Background: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options.

Patients and methods: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs.

Results: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to αCD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were primarily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications.

Conclusion: Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to αCD38 mAb therapy and could help address the unmet clinical need in these high-risk patients.

Keywords: Heavily pre-treated disease; High-risk; Oral selective inhibitor of nuclear export; Relapsed/refractory; Triplet.

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Conflict of interest statement

Acknowledgments Karyopharm funded the study and provided selinexor supply. Sharon Furman-Assaf, supported by funding from Karyopharm, provided drafts and editorial assistance to the authors during the preparation of this manuscript. This work was supported by Karyopharm Therapeutics Inc. Karyopharm Therapeutics was the sponsor of this study and was responsible for study design, the collection of data, analysis of data, interpretation of data, writing of the report, and the decision to submit the paper for publication. The corresponding author had full access to all data and had the final responsibility for the decision to submit for publication with the agreement of all other authors.

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Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies

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Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies

Authors

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Abstract

Conflict of interest statement

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