SAFETY AND EFFICACY OF COMBINATION OF SELINEXOR, DARATUMUMAB, AND DEXAMETHASONE (SDD) IN PATIENTS WITH MULTIPLE MYELOMA (MM) PREVIOUSLY EXPOSED TO PROTEASOME INHIBITORS AND IMMUNOMODULATORY DRUGS
Author(s): ,
Cristina Gasparetto
Affiliations:
Duke University Cancer Center,Durham, North Carolina,United States
,
Suzanne Lentzsch
Affiliations:
Columbia University,New York, NY,United States
,
Gary Schiller
Affiliations:
David Geffen School of Medicine at UCLA,Los Angeles, CA,United States
,
Natalie Callander
Affiliations:
University of Wisconsin, Carbone Cancer Center,Madison, WI,United States
,
Sascha Tuchman
Affiliations:
University of North Carolina,Chapel Hill, NC,United States
,
Christine Chen
Affiliations:
Princess Margaret Cancer Center,Toronto, Ontario,Canada
,
Darrell White
Affiliations:
Dalhousie University,Halifax, Nova Scotia,Canada
,
Rami Kotb
Affiliations:
Cancer Care Manitoba,Winnipeg, Manitoba,Canada
,
Heather Sutherland
Affiliations:
Vancouver General Hospital,Vancouver, British Columbia,Canada
,
Michael Sebag
Affiliations:
Royal Victoria Hospital,Montreal, Quebec,Canada
,
Muhamed Baljevic
Affiliations:
University of Nebraska Medical Center,Omaha, NE,United States
,
William Bensinger
Affiliations:
Swedish Cancer Center,Seattle, WA,United States
,
Richard LeBlanc
Affiliations:
Hôpital Maisonneuve-Rosemont,Montreal, Quebec,Canada
,
Chris Venne
Affiliations:
Cross Cancer Institute,Edmonton, Alberta,Canada
,
Nizar Bahlis
Affiliations:
Southern Alberta Cancer Research Institute,Calgary, Alberta,Canada
,
Karla Rodriguez-Lopez16
Affiliations:
Karyopharm Therapeutics Inc,Newton MA,United States
,
Heidi Sheehan
Affiliations:
Karyopharm Therapeutics Inc,Newton MA,United States
,
Jean-Richard Saint-Martin
Affiliations:
Karyopharm Therapeutics Inc,Newton MA,United States
,
Jatin Shah
Affiliations:
Karyopharm Therapeutics Inc,Newton MA,United States
,
Sharon Shacham
Affiliations:
Karyopharm Therapeutics Inc,Newton MA,United States
,
Michael Kauffman
Affiliations:
Karyopharm Therapeutics Inc,Newton MA,United States
Brea Lipe
Affiliations:
University of Rochester Medical College,New York, NY,United States
EHA Library. J. Gasparetto C. Jun 16, 2019; 267360; S1606
Cristina J. Gasparetto
Cristina J. Gasparetto
Contributions
×
Abstract

Abstract: S1606

Type: Oral Presentation

Presentation during EHA24: On Sunday, June 16, 2019 from 09:00 - 09:15

Location: Auditorium

Background
Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Selinexor in combination with dexamethasone (dex) has demonstrated a 26.2% overall response rate (ORR) in patients (pts) with triple-class refractory myeloma (defined as refractory to an immunomodulatory drug (IMiD), proteasome inhibitor (PI), and CD-38 monoclonal antibody [mAb]) including deep responses with very good partial response (VGPR) and 2 pts in a stringent complete response (sCR) (minimal residual disease negative). Daratumumab (Dara), an anti-CD38 mAb, is approved for the treatment of heavily pretreated MM is limited by short progression-free survival (PFS) and an ORR of ~21% in quad-refractory MM.

Aims
The objectives of the study were to determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D), and to assess the safety, tolerability, and preliminary efficacy of the combination of SDd in pts with PI/IMiD refractory MM.

Methods
This is amulticenter, open-label, phase 1/2b study with a dose escalation and expansion phase.Pts were eligible if they had received ≥3 prior lines of anti-myeloma therapy, including a PI and an IMiD or whose MM is refractory to a PI and IMiD. In the expansion phase, pts’ prior dara therapy was exclusionary. Selinexor was dose-escalated in 2 concurrent cohorts: once-weekly (QW, at 100 mg) or twice-weekly (BIW, at 60 mg). Dara was administered at 16 mg/kg IV (recommended schedule) and dex at 40 mg QW or 20 mg BIW. In the expansion phase, pts were to receive the RP2D.

Results
As of February 20th2019, 30 pts (16 male/14 female) have been enrolled. Three pts have been enrolled into the 60 mg BIW and 27 pts in the 100 mg QW cohorts. The median age was 69 years and the median number of prior treatment regimens was 3 (range, 2 – 10). Common treatment-related adverse events (all grades, Grades 3/4) included: thrombocytopenia (66%, 48%), nausea (66%, 3%), fatigue (55%, 14%), anemia (52%, 31%), leukopenia (48%, 31%), and neutropenia (48%, 24%). Two dose-limiting toxicities (DLTs) were reported in the 60 mg BIW cohort: Grade 3 thrombocytopenia and Grade 2 fatigue requiring dose reduction in selinexor to 100 mg QW. In the 100 mg QW escalation cohort (n=6), no DLTs occured.Based on tolerability and efficacy, the RP2D of SDd is selinexor 100 mg, dara 16 mg/kg, and dex 40 mg, administered QW. A total of 28 pts were evaluable for response.In dara naïve pts (n=26), the ORR was 77% (9 VGPR, 8 partial response, 3 unconfirmed partial response). In the 2 pts with dara refractory MM, there was one progressive disease and one stable disease.

Conclusion
Selinexor 100 mg QW can be combined safely with dara (per approved dosing) and dex to produce a deep and durable response warranting further investigation in pts with relapsed refractory MM. The ORR was 77% in pts who had not received prior dara or selinexor. Enrollment in the expansion arm is expected to be completed in March 2019 and full study results will be presented.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): CD38, Monoclonal antibody, Multiple myeloma, Tumor suppressor

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies