Abstract: Introduction: Treatment of older or frail patients (pts) with multiple myeloma (MM) remains challenging due to impaired organ function, underlying comorbidities, need for convenient regimens and burden of care, all of which impact the tolerability of anti-MM therapies. In the STORM study, selinexor plus dexamethasone (sel-dex) demonstrated anti-MM activity with an ORR of 26.2% and similar safety across all age groups in pts with triple-class refractory MM (Chari et al. NEJM 2019, Gavriatopoulou et al. IMW 2019). In the phase 3 BOSTON study, the combination of weekly sel-dex with once weekly bortezomib (SVd) was superior to standard twice weekly bortezomib and dex (Vd) across all efficacy endpoints in pts with MM who had received 1-3 prior therapies. Furthermore, while conferring a longer PFS and higher ORR than Vd, SVd was associated with significantly reduced rates of peripheral neuropathy (PN), the most clinically relevant toxicity associated with bortezomib that limits long term administration, especially in older and/or frail pts. Here we present results of subgroup analyses of the BOSTON study to evaluate the safety and efficacy of SVd versus Vd based on age and frailty index. Methods: Pts enrolled in BOSTON were assigned (1:1) to once weekly oral sel (100 mg) plus once weekly subcutaneous (SC) bortezomib (1.3 mg/m2) and dex (20 mg BIW) in the SVd arm or to standard twice weekly SC bortezomib (1.3 mg/m2) and dex (20 mg QIW) in the Vd arm. Treatment was administered in both arms until disease progression. The primary endpoint was PFS, as assessed by an Independent Review Committee. For these analyses, pts were assigned to 2 groups based on age ( & lt;65 and ≥65 years) and Frailty Score categories (frail and fit). Frailty Score was assessed using baseline characteristics including age, Charlson Comorbidity Index, and Eastern Cooperative Oncology Group performance status (Facon et al. Leukemia 2019). Results: Of the 402 enrolled pts, 241 (60%) were ≥65 years (SVd=109, Vd=132). Of these, 81 (37%) were ≥75 and 106 (44%) were categorized as frail (SVd=51, Vd=55). Baseline pt and disease characteristics were well balanced between treatment arms in the subgroups. PFS was prolonged in both age groups with SVd compared with Vd. In ≥65, PFS was 21.0 vs 9.5 months (HR, 0.55; 95% CI, 0.37-0.83; P=0.0018) and in & lt;65, PFS was 12.2 vs 9.4 months (HR, 0.74; 95% CI, 0.41-1.10; P=0.07). The PFS benefit of SVd was sustained and comparable in the frail pts: 13.9 vs 9.5 months (HR, 0.69; 95% CI, 0.40-1.17; P=0.08); and in the fit pts: 13.2 vs 9.4 months (HR, 0.66; 95% CI, 0.47-0.93; P=0.0076) (Figure). The ORR was significantly improved with SVd in those ≥65 (76.1% vs 64.4%; P=0.0243) and & lt;65 (76.7% vs 58.7%, P=0.0071). The ORR was improved with SVd in both the frail (69.7% vs 60.9%; P=0.14) and fit groups (79.8% vs 62.9%; P=0.0011). Overall survival was 24.8 months and 23.5 months in the Vd arm in the ≥65 and frail pts respectively and was not reached in any of the subgroups in the SVd arm. There were more deaths in the ≥65 (30% [SVd 23%, Vd 36%]) and frail groups (35% [SVd 26%, Vd 44%] ) compared with the & lt;65 (23% [SVd 26%, Vd 20%]) and fit groups (24% [SVd 23%, Vd 24%] ). Similar to the overall population, the most common grade ≥3 adverse events (AEs) were thrombocytopenia, anemia, pneumonia and fatigue. In the SVd arm, the incidence of AEs was comparable across subgroups except for a higher incidence of fatigue in ≥65 versus & lt;65 (17% vs 8%) and pneumonia in the frail versus fit (19% vs 7%). The incidence of serious AEs in the SVd versus Vd arms was (56% vs 45%) and (47% vs 25%) in ≥65 and & lt;65 and (59% vs 48%) and (48% and 33%) in the frail and fit groups, respectively. Treatment discontinuation due to AEs occurred in 21% pts on SVd versus 16% on Vd in ≥65 and in 18% on SVd versus 11% on Vd in the frail group. Grade ≥ 2 PN rates were lower in the SVd compared with Vd arms in all subgroups with significant differences in ≥65 (22% vs 37%; P=0.0060) and frail groups (15% vs 44%; P=0.0002). Conclusions: In pts with previously treated MM, the once weekly SVd regimen led to prolonged PFS, improved response rates and rates of PN regardless of age and frailty score compared to standard twice weekly Vd. Non-PN AEs were higher with triplet than doublet therapy, but most of the AEs were reversible and treatable. There were fewer deaths on SVd in pts ≥65 and in frail pts compared to Vd. Once weekly SVd is a potent and convenient treatment option for pts with previously treated MM, including those who are ≥65 years and/or frail. Figure Disclosures Auner: Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Dimopoulos:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Leleu:Incyte: Honoraria; Merck: Honoraria; AbbVie: Honoraria; Carsgen: Honoraria; Janssen: Honoraria; Novartis: Honoraria; BMS-celgene: Honoraria; Amgen: Honoraria; GSK: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; Oncopeptide: Honoraria. Hajek:Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pharma MAR: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy. Jagannath:Sanofi: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Moreau:Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Honoraria. Levy:Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Bahlis:BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mateos:EDO Mundipharma: Honoraria; Seattle Genetics: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; GlaxoSmithKline: Honoraria; Adaptive Biotechnologies: Honoraria; Takeda: Honoraria; Roche: Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Joshi:Karyopharm Therapeutics Inc: Consultancy. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

Abstract: Background: Once multiple myeloma (MM) becomes refractory to αCD38 mAb, pts have limited effective treatment options and poor prognoses. With standard therapies, overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (PFS) - 3.4 months and median overall survival (OS) - 9.3 months (Gandhi et al, Leukemia, 2019). Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins. XPO1 is required for MM cell growth, is associated with poor prognosis and mediates resistance to standard MM and other anticancer therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved for patients (pts) with previously treated MM as well as DLBCL. The doublet SEL-dexamethasone (Xd) achieved ORR ~26% in triple-class (Immunomodulatory drug [IMiD] , proteosome inhibitor [PI], αCD38 mAb) refractory MM and improved OS over matched cohorts in community (Richardson et al, eJHaem, 2021) and academic (Cornell et al, AJH, 2020) settings. Hence, SEL-based triplets could be more effective in this triple class-treated population. We analyzed the efficacy and safety of SEL-containing triplets in pts in the STOMP study who were previously treated with regimens containing αCD38 mAb. Methods: STOMP is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various combinations (NCT02343042). Here, we analyzed ORR, clinical benefit rate (CBR), duration of response (DOR), PFS, OS, and treatment-emergent adverse events (TEAEs) of pts who received Xd plus pomalidomide (XPd, n=23) or carfilzomib (XKd, n=23) after prior therapy with αCD38 mAb. Results: Among 46 pts treated, median age was 64 yrs (XPd), 70 yrs (XKd), females 57% (XPd) and 39% (XKd), median time from diagnosis was 5 yrs, and median number of prior regimens 4 (range, 2-10). All pts were previously treated with a PI and IMiD and αCD38 mAb; 78% (XPd) and 52% (XKd) had triple refractory MM. Prior treatment with αCD38 mAb included daratumumab (XPd: 91%, XKd: 100%) and isatuximab (XPd: 9%); 52% (XPd) and 74% (XKd) had αCD38 mAb in their most recent prior regimen. Refractoriness to daratumumab was documented in 87% (XPd) and 96% (XKd); isatuximab in 9% (XPd). Median durations from end of most recent αCD38 mAb therapy to first dose of study treatment were 8 weeks (XPd), 4 weeks (XKd). Among evaluable pts, ORR and CBR were 52% and 76%, respectively in the XPd arm (n=21; 2 pts were not efficacy evaluable) and 65% and 74%, respectively in the XKd arm. In the XPd arm median PFS was 8.7 months (95% CI: 7.6, NE), median DOR was 7.9 months (95% CI: 3.9, NE), and median OS was 21.8 months (95% CI: 8, NE). In the XKd arm median PFS was 15 months (95% CI: 12.0, NE), median DOR was 13.1 months (95% CI: 10.2, NE), and median OS was 33.0 months (95% CI: 20.4, NE). Among the evaluable pts, response to SEL-containing triplets compared favorably to the prior αCD38 mAb-containing regimen used at least 1 line earlier: XPd arm (n=21), ORR 52% vs 58% for prior regimen, CBR 76% vs 58%, median PFS 8.7 months (95% CI: 7.6, NE) vs 10.2 months (95% CI: 5.2, 20.5); XKd arm (n=23), ORR 65% vs 52%, CBR 74% vs 57%, median PFS 15.0 months (95% CI: 12.0, NE) vs 8.5 months (95% CI: 5.9, 17.3). The most common hematological TEAEs (total; grade≥3) were thrombocytopenia (XPd: 35%; 30%; XKd: 78%; 39%), anemia (XPd: 57%; 39%; XKd: 57%; 22%), and neutropenia (XPd: 57%; 48%; XKd: 35%; 4%). Other common TEAEs (total; grade≥3) were nausea (XPd: 74%; 0; XKd: 74%; 4%), fatigue (XPd: 61%; 4%; XKd: 52%; 4%) and decreased appetite (XPd: 48%; 4%; XKd: 48%; 4%). No cases of severe bleeding with thrombocytopenia occurred. Three pts (13%, all XPd) had febrile neutropenia (the outcome of which was fatal in 1 pt, deemed related to SEL and pomalidomide). TEAEs were managed with standard supportive care and dose modifications. Summary/Conclusion: XPd and XKd administered to pts with heavily pretreated MM, including prior αCD38 mAb therapy, exhibit tolerability and comparable effectiveness to that of the prior αCD38 mAb-containing regimen. These results suggest that the use of SEL-containing triplets, implementing the novel XPO1 inhibition mechanism, can provide prolonged disease control with good tolerability rather than recycling previously utilized drugs/mechanisms. The all oral XPd regimen will be evaluated in Study EMN29 against elotuzumab-Pd in patients who have received lenalidomide, a PI and an αCD38 mAb. Disclosures Lentzsch: Janssen: Consultancy; AbbVie: Consultancy; Celularity: Consultancy; GSK: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Oncopeptides: Consultancy; Caelum Biosciences: Consultancy, Current holder of individual stocks in a privately-held company; Ossium Health: Consultancy; Magenta Therapeutics: Current equity holder in publicly-traded company; Kadmon: Current equity holder in publicly-traded company. Lipe: Seagen Inc.: Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; sanofi: Consultancy; GlaxoSmithKline: Consultancy; amgen: Research Funding; Cellectar: Research Funding; Karyopharm: Research Funding; Harpoon: Research Funding. Tuchman: Karyopharm: Research Funding; Shattuck Labs: Consultancy; Sanofi / Genzyme: Consultancy, Research Funding; Caelum: Consultancy, Research Funding; Oncopeptides: Consultancy. Bahlis: Takeda: Consultancy, Honoraria; Genentech: Consultancy; Amgen: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Bensinger: BMS, Janssen, Poseida, Regeneron, Trillium: Research Funding; Amgen, BMS, Janssen, Sanofi: Speakers Bureau. Sebag: Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers-Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Janssen: Research Funding. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Monge: Bristol Myers Squibb: Consultancy; Karyopharm Therapeutics: Research Funding. Gasparetto: Karyopharm Therapeutics Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Oncopeptite: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Connect Registry: Membership on an entity's Board of Directors or advisory committees. Baljevic: Exelixis: Research Funding; Karyopharm: Other: Advisory Board; BMS/Celgene: Other: Advisory Board; Janssen Research: Other: Advisory Board; Oncopeptides: Other: Advisory Board; BMS/Celgene: Consultancy; Amgen: Research Funding. Venner: Janssen: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; BMS: Honoraria; GSK: Honoraria; Takeda: Honoraria. White: Amgen, Antengene, BMS/Celgene, Forus, GSK, Janssen, Karyopharm, Sanofi, Takeda: Consultancy, Honoraria. Kotb: Takeda: Honoraria; Karyopharm: Current holder of individual stocks in a privately-held company; Amgen: Honoraria; BMS: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Akcea: Honoraria; Pfizer: Honoraria. Chen: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Schiller: Celator: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Mateon: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Tolero: Research Funding; Constellation Pharmaceuticals: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Sangamo: Research Funding; Trovagene: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Cyclacel: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Forma: Research Funding; Daiichi-Sankyo: Research Funding; Bio: Research Funding; Ono-UK: Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Delta-Fly: Research Funding; FujiFilm: Research Funding; Deciphera: Research Funding; Arog: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; PrECOG: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Onconova: Research Funding; Astellas: Honoraria, Research Funding, Speakers Bureau; Karyopharm: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Regimmune: Research Funding; Ono: Consultancy; Samus: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Actuate: Research Funding; Actinium Pharmaceuticals, Inc: Research Funding; Geron: Research Funding; Genentech-Roche: Research Funding; Gamida Cell Ltd.: Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Elevate: Research Funding; Novartis: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Madan: Karyopharm: Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Sanofi: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Speakers Bureau. Leblanc: Sanofi Canada: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Canada: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Research Funding; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. DeCastro: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Bentur: Karyopharm Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Van Domelen: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) .

Abstract: Background : Selinexor (SEL) is a novel, first-in-class oral selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, ultimately causing cell death in cancer cells. SEL 80 mg and dexamethasone (dex) 20 mg, both twice weekly (BIW), received accelerated approval from the FDA for patients (pts) with relapsed refractory multiple myeloma (RRMM). SEL continues to be evaluated in earlier lines of therapy with once weekly administration and in combination regimens. The SVd regimen with once weekly (QW) oral SEL (100 mg), dexamethasone (dex) and QW bortezomib (BOR) had significantly increased progression free survival (PFS) and overall response rate (ORR) with significantly reduced peripheral neuropathy as compared to standard BIW BOR/dex (Vd) in the phase III BOSTON study. The combination of lenalidomide (LEN) and dex (Rd) is an approved regimen in RRMM and newly diagnosed MM (NDMM) with an ORR of 70-76% in RRMM but a low complete response rate. SEL showed synergistic antitumor activity with LEN in a MM xenograft model. Therefore, we hypothesized that the all oral combination of weekly SEL with standard Rd (i.e., SRd) could improve the efficacy compared with Rd in pts with RRMM and NDMM with acceptable toxicity profile. Methods: STOMP is a phase 1b/2 multicenter, open-label, clinical trial with the goals of determining the maximum tolerated dose, the recommended phase 2 dose (RP2D), efficacy and safety of SRd in pts with RRMM or NDMM. For RRMM, SEL was dose escalated in two regimens QW (starting at SEL 80 mg) or BIW (starting at 60 mg), LEN 25 mg PO daily and DEX 20 mg BIW or 40 mg QW. Results: As of June 1, 2020, 24 pts (13 male, 11 female) with RRMM were enrolled. The median age was 67 years (range, 49-84) and the median number of prior lines of therapy was 1.5 (range, 1 - 8). In the 60 mg BIW dosing, 4 pts experienced dose limiting toxicities (DLTs) out of 5 pts dosed (2 thrombocytopenia, 1 anorexia, 1 & gt;25% missed dose due to unrelated QT interval prolongation). In the 80 mg QW dosing, 2 pts experienced DLTs out of 6 pts (both grade 4 thrombocytopenia). In the 60 mg QW dosing, no DLTs were observed. Based on these data, the RP2D of SRd was determined to be: SEL 60 mg QW, LEN 25 mg QD and DEX 40 mg QW. Common treatment related adverse events (TRAEs) (All Grades, ≥3) were thrombocytopenia (71%, 63%), neutropenia (63%, 63%), nausea (58%, 4%), fatigue (54%, 17%), decreased appetite (50%, 8%), and weight loss (42%, 8%). Amongst the 20 pts with RRMM where efficacy was evaluable, previously treated/documented refractory rates were: bortezomib (100%, 45%), LEN (40%, 25%), daratumumab (20%, 20%), and pomalidomide (20%, 20%). Amongst the LEN naïve pts (n=12), the ORR was 92% including 1 stringent complete response [sCR], 4 very good partial responses [VGPR] and 6 partial responses [PR, 2 unconfirmed]). PFS in LEN naïve pts has not been reached with a median follow-up period of 7.8 months. In the pts with prior LEN treatment (n=8), the ORR was 13%. Based on the high levels of activity of SRd in LEN naïve pts, 8 pts (4 males and 4 females) with NDMM were enrolled at the RP2D. The median age was 74 (range: 51-86) years. No DLTs were observed in 5 DLT evaluable pts. Common TRAEs (All Grades, ≥3) were thrombocytopenia (63%, 38%), neutropenia (75%, 75%), fatigue (63%, 50%), nausea (50%, 0%), weight loss (63%, 0%), and decreased appetite (13%, 13%). All 7 efficacy evaluable pts achieved a response, an ORR of 100%, including 1 CR, 4 VGPR, and 2 PR. With a median follow-up of 10.2 months, median PFS has not been reached. Out of these 7 pts, three pts withdrew consent to transit to successful autologous stem cell collection and transplantation. Conclusions: The all oral combination of SRd with once weekly SEL 60 mg, LEN 25 mg QD and DEX 40 mg QW was established as the RP2D for pts with RRMM or NDMM. The safety profile was similar in both settings. All TRAEs were manageable with adequate supportive care and/or dose modification. The all oral combination of SRd has demonstrated ORR of 92% in pts with LEN naïve RRMM and ORR of 100% in pts with NDMM, warranting further investigation of SRd with or without additional anti-MM agents for the treatment of pts with NDMM. Disclosures White: Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria. LeBlanc:Celgene: Research Funding; Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Baljevic:NCCN Hematologic Malignancies Congress: Honoraria; MediCom Myeloma CME: Honoraria; Amgen: Research Funding; Exelixis: Research Funding; Celgene Corporation / BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Putnam Associates: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gerson Lehrman Group: Consultancy, Membership on an entity's Board of Directors or advisory committees; AlphaSights: Consultancy, Membership on an entity's Board of Directors or advisory committees; Coleman: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics Inc.: Honoraria. Bahlis:Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Lentzsch:Celularity: Consultancy; Sorrento: Consultancy; Janssen: Consultancy; Caelum Biosciences: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Mesoblast: Divested equity in a private or publicly-traded company in the past 24 months; Sanofi: Research Funding; Magenta: Current equity holder in private company; Karyopharm: Research Funding. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Chen:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding. Lipe:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Tuchman:Roche: Research Funding; Oncopeptides: Consultancy; Janssen: Research Funding; Amgen: Research Funding; Sanofi: Honoraria, Research Funding; Caelum: Honoraria; Karyopharm: Honoraria, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau. Sutherland:Janssen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy; Amgen: Consultancy. Kotb:Merck: Honoraria, Research Funding; Karyopharm: Current equity holder in publicly-traded company; Takeda: Honoraria; Celgene: Honoraria; Sanofi: Research Funding; Amgen: Honoraria; Janssen: Honoraria. Sebag:Amgen: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria; Takeda: Honoraria. Callander:Cellectar: Research Funding; University of Wisconsin: Current Employment. Bensinger:BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rossi:Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Sheehan:Karyopharm Therapeutics Inc: Current Employment. Van Domelen:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Zhou:Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Kazuharu:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Schiller:Ariad: Research Funding; Actinium: Research Funding; Jazz Pharmaceuticals: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Kaiser Permanente: Consultancy; Trovagene: Research Funding; Tolero: Research Funding; Sangamo: Research Funding; Samus: Research Funding; Regimmune: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Karyopharm: Research Funding; Kite Pharma: Research Funding; Mateon: Research Funding; MedImmune: Research Funding; Onconova: Research Funding; Cyclacel: Research Funding; Daiichi Sankyo: Research Funding; Deciphera: Research Funding; Astellas Pharma: Honoraria, Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Celator: Research Funding; Abbvie: Research Funding; Constellation: Research Funding; Ono Pharma: Consultancy; Novartis: Consultancy, Research Funding; Stemline: Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy; Gilead: Speakers Bureau; Sanofi: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Current equity holder in publicly-traded company, Research Funding; DeltaFly: Research Funding; Forma: Research Funding; Gamida: Research Funding; FujiFilm: Research Funding; Genentech-Roche: Research Funding; Geron: Research Funding.

Abstract: Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m 2 ) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT. Trial registration : ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562 .

Abstract: There is a lack of consensus on therapy sequencing in previously treated multiple myeloma, particularly after anti‐B‐cell maturation antigen (BCMA) therapy. Earlier reports on selinexor (X) regimens demonstrated considerable efficacy in early treatment, and after anti‐BCMA‐targeted chimeric antigen receptor‐T cell therapy. Here, we present data from 11 heavily pretreated patients who predominantly received BCMA‐antibody‐drug conjugate therapy. We observe that X‐containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survival compared to patients’ prior anti‐BCMA therapies, despite being used later in the treatment course. In an area of evolving unmet need, these data reaffirm the efficacy of X‐based regimens following broader anti‐BCMA therapy.

Abstract: In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1–3 prior regimens were randomized to once‐weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib‐dexamethasone (XVd) or twice‐weekly bortezomib‐dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression‐free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high‐risk (presence of del[17p] , t[4;14], t[14;16] , or ≥4 copies of amp1q21) cytogenetics (XVd, n  = 70; Vd, n  = 71), and 261 (64.9%) exhibited standard‐risk cytogenetics (XVd, n  = 125; Vd, n  = 136). Among patients with high‐risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p  = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p  = 0.004). In the standard‐risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p  = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p  = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.

Abstract: Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once‐weekly selinexor and bortezomib with low‐dose dexamethasone (XVd) improved PFS and ORR compared with standard twice‐weekly bortezomib and moderate‐dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status ( 〈 65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p  = .024), ≥VGPR (OR, 1.68, p  = .027), PFS (HR 0.55, p  = .002), and improved OS (HR 0.63, p  = .030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p  = .08) and OS (HR 0.62, p  = .062). Significant improvements were also observed in patients 〈 65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year‐old (22% vs. 37%; p  = .0060) and frail patients (15% vs. 44%; p  = .0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients 〈 65 and ≥65 and in nonfrail and frail patients with previously treated MM.

Abstract: Introduction Selinexor is a first-in-class, oral, potent selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, leading to cancer cell apoptosis. Selinexor has demonstrated antimyeloma activity in triple class refractory multiple myeloma (MM) [Chari et al. NEJM 2019]. Selinexor synergizes with proteasome inhibitors (PIs) in PI-sensitive and -resistant cell lines and produces high response rates in patients with PI refractory and non-refractory MM (Bahlis et al. Blood 2018). In the phase 3 BOSTON study, the combination of once weekly (QW) selinexor, QW bortezomib, and dexamethasone (SVd) in patients who had received 1-3 prior therapies led to a significantly longer (47%) median progression-free survival (PFS) of 13.93 vs 9.46 months, with a hazard ratio of 0.70 (P=0.0075) compared to standard twice weekly bortezomib and dexamethasone (Vd). In addition, SVd regimen produced higher response rates and deeper responses (ORR: 76.4% vs 62.3% and ≥CR 16.9% vs 10.2%) compared with Vd. The benefit with SVd was observed across all efficacy endpoints and was associated with lower incidence and severity of bortezomib-induced peripheral neuropathy. Here we analyzed the effect of prior PI therapy (bortezomib, carfilzomib, ixazomib) on the efficacy and safety of SVd compared with Vd. Methods BOSTON is an open-label, randomized phase 3 study in patients with MM comparing SVd (QW oral selinexor 100 mg, QW subcutaneous bortezomib 1.3 mg/m2, and BIW oral dexamethasone 20 mg), versus Vd (BIW bortezomib 1.3 mg/m2 and QIW dexamethasone 20 mg). Patients previously treated with a PI must have had at least a partial response (PR) to the PI and 6 months since the last PI regimen. The study primary end point was PFS. Here we report subgroup analysis of treatment outcomes based on prior PI treatment. Results Subgroups consisted of PI naïve patients (n=95; 24%) and patients with prior PI treatment (n=307; 76%). Both the subgroups and study arms were comparable for baseline patient demographic and disease characteristics. However, those with prior PI treatment more frequently had a previous stem cell transplant (38% vs 24%) or 3 lines of prior anti MM therapy (21% vs 13%). Median PFS was improved with SVd compared with Vd in both the PI naïve group (PFS not reached (NR) vs 9.7 months; HR 0.2585 [95% CI, 0.1116-0.5988] ; P=0.0003) and in the PI treated group (11.7 vs 9.4 months; HR 0.7839 [95% CI, 0.5791-1.0612]; P=0.06). Other efficacy endpoints are shown in the table. Peripheral neuropathy ≥grade 2 (a secondary study endpoint) was less frequent in the SVd compared with the Vd arm (PI naïve: 25.5%, Vd 43.8%, P=0.0302; PI treated: SVd 19.6%, Vd 31.4%, P=0.0092). Adverse events of ≥grade 3 occurred in 71% of patients in the PI naïve group (SVd 77%, Vd 65%) and 74% of patients in the PI treated group (SVd 88%, Vd 60%). Thrombocytopenia was more frequent in patients in the SVd arms (PI naïve: SVd 32%, Vd 13%; PI treated: SVd 42%, Vd 19%) as was anemia (PI naïve: SVd 15%, Vd 6%; PI treated: SVd 16%, Vd 12%), and fatigue (PI naïve: SVd 15%, Vd 2%; PI treated: SVd 13%, Vd 1%). Conclusions The once-weekly SVd combination was associated with significant clinical benefit and reduced peripheral neuropathy as compared with standard twice-weekly Vd in patients with MM and 1-3 prior therapies, regardless of prior therapy with a PI. However, the benefits of SVd over Vd were more pronounced in patients who had never been treated with a PI (PFS HR 0.26), suggesting that selinexor could be an optimal partner for combining with weekly bortezomib as the first PI-containing MM regimen. Figure 1 Disclosures Mateos: Roche: Honoraria; Seattle Genetics: Honoraria; EDO Mundipharma: Honoraria; Adaptive Biotechnologies: Honoraria; GlaxoSmithKline: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Auner:Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Leleu:AbbVie: Honoraria; GSK: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria; Oncopeptide: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria. Hajek:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, Janssen: Consultancy; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses; Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Moreau:Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Honoraria. Levy:Karyopharm,Takeda, BMS: Consultancy, Honoraria, Speakers Bureau. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:Karyopharm: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis:Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; AbbVie: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.