Selinexor containing regimens in patients with multiple myeloma (MM) previously treated with anti-CD38 monoclonal antibodies (αCD38 mAbs).

Authors

null

Cristina Gasparetto

Duke University Cancer Center, Durham, NC

Cristina Gasparetto , Brea Lipe , Sascha Tuchman , Nizar J. Bahlis , Heather J. Sutherland , Adriana C. Rossi , Suzanne Lentzsch , Muhamed Baljevic , Suzanne Lentzsch , Natalie Scott Callander , Christopher P. Venner , Michael Sebag , Darrell White , Rami Kotb , Christine Chen , Noa Biran , Sumit Madan , Richard LeBlanc , Andrew DeCastro , Gary J. Schiller

Organizations

Duke University Cancer Center, Durham, NC, University of Rochester, Rochester, NY, The University of North Carolina at Chapel Hill-Lineberger Comprehensive Cancer Center, Chapel Hill, NC, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, Leukemia/Bone Marrow Transplant Program, University of British Columbia, Vancouver, BC, Canada, NYPH Weill Cornell, New York, NY, Columbia University, New York, NY, Department of Internal Medicine, Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE, Division of Hematology/Oncology, Columbia University, University of Wisconsin, Carbone Cancer Center, Madison, WI, Cross Cancer Institute, Edmonton, AB, Canada, McGill University Health Centre, Montréal, QC, Canada, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada, Cancer Care Manitoba, Winnipeg, MB, Canada, Princess Margaret Cancer Center, Toronto, ON, Canada, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, Banner MD Anderson Cancer Center, Gilbert, AZ, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada, Karyopharm Therapeutics, Newton, MA, University of California, Los Angeles, CA

Research Funding

Pharmaceutical/Biotech Company
Karyopharm Therapeutics Inc

Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins, is required for MM growth, is associated with poor prognosis in MM and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to αCD38 mAb, pts have limited effective treatment options and poor prognosis. Overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (mPFS) is 3.4 months (m), and median overall survival (mOS) is 8.6 m. The doublet SEL-dex (Xd) has shown ORR ̃26% in triple-class (IMID, PI, αCD38 mAb) refractory MM; SEL-based triplets could be more effective in this population. Methods: STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations. Here, we retrospectively analyzed the efficacy and safety of SEL-containing triplets in pts previously treated with αCD38 mAbs. Pts received SEL-dex (Xd) plus pomalidomide (XPd, n = 19), bortezomib (XVd, n = 4), lenalidomide (XRd, n = 4), daratumumab (XDd, n = 2) or carfilzomib (XKd, n = 18). ORR, mOS, mPFS and adverse events (AEs) were analyzed. Results: Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM refractory to aCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-exposed, 43% and 15% had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent aCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts, 59% in the XPd arm (n = 17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among pts with quad-refractory MM and evaluable efficacy. Among all evaluable pts mPFS was 8.8 m (95% CI: 4.9, NE) and mOS was 20.4 m (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy was similar to that regimen: ORR 52% vs. 45%, mPFS 8.8 vs. 9.3 m. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications. Conclusions: SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical control, mOS was much higher among these patients. Further investigation is warranted. Clinical trial information: NCT02343042

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies

Sub Track

Multiple Myeloma

Clinical Trial Registration Number

NCT02343042

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr e20020)

DOI

10.1200/JCO.2021.39.15_suppl.e20020

Abstract #

e20020

Abstract Disclosures