Abstract: Introduction: Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that selectively binds and inactivates XPO1, therefore forcing the nuclear retention and re-activation of cell cycle regulators such as p53, FOXO, IkB, and Rb. Selinexor in combination with low dose dexamethasone (Sel-dex) was recently approved based on data from the STORM study, which induced an overall response rate (ORR) of 26.2% in patients with penta-exposed, triple-class refractory multiple myeloma (TCR-MM). Patients with TCR-MM often present with plasmacytomas along with serological markers of MM. Methods: Here we analyzed the effects of Sel-dex in patients from the STORM study who had baseline plasmacytomas. Results: 122 patients were in enrolled in the STORM study including 27 with a baseline plasmacytoma. The majority of plasmacytomas were soft tissue (22 patients) and 5 patients had soft tissue disease extension from a bone (rib (2), iliac (2), sacral vertebral). The median age of patients with plasmacytomas was 64 years, the median prior therapies were 7 (range 4 - 15), and 8/27 patients with a plasmacytoma had high risk cytogenetics. Of the 27 patients, 11 patients did not have a follow up plasmacytoma assessment: 6 were not evaluable for response as they came off therapy due to clinical progression and/or adverse events, 4 had stable disease (SD) with no evidence of plasmacytoma change, and 1 had progressive disease (PD) on serum M-protein with no evidence of plasmacytoma change. Sixteen of the 27 patients did have follow-up plasmacytoma assessments (methods of measurements included PET, CT, MRI or Clinical). The median days from baseline plasmacytoma evaluation to follow up was 41 days (range 22 - 119). Five patients had objective responses, based upon para-protein and plasmacytoma reductions according to IMWG criteria (1 very good partial response [VGPR], 4 partial responses [PR] ) for an ORR of 18.5%. In addition, 2 patients had a minimal response (MR), 4 had SD and 5 had objective PD. Among the 5 patients with ≥PR, 3 plasmacytomas completely resolved, 1 showed near complete resolution, and another showed size reduction with no metabolic activity on PET. Of the 2 patients with a MR, 1 plasmacytoma completely resolved and 1 showed reduced PET uptake. Among the 4 patients with SD, 1 plasmacytomas completely resolved, 1 increased in size and 2 had unknown outcomes as they were assessed clinically. Among the 5 patients with PD, 1 plasmacytomas decreased in size, 1 increased in size, and 3 had unknown outcomes as they were assessed clinically. Conclusions: Of the 16 patients with TCR-MM and a follow up plasmacytoma assessment enrolled on STORM, 9/16 of the plasmacytomas either completely resolved or decreased in size and/or metabolic activity. Effects on plasmacytomas occurred in patients with objective responses (≥PR), as well as in patients with MR, SD and PD. These observations support the finding that Sel-dex is active in patients with plasmacytomas and heavily pretreated TCR-MM. Disclosures Yee: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Karyopharm: Consultancy; Adaptive: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding. Huff:Member of Safety Monitoring Board for Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees; Karyopharm, Sanofi, MiDiagnostics: Consultancy. Chari:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Oncoceutics: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; GlaxoSmithKline: Research Funding; Novartis Pharmaceuticals: Research Funding. Vogl:Active Biotech: Consultancy; Janssen: Consultancy; Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Gavriatopoulou:Genesis: Honoraria, Other: Travel expenses; Amgen: Honoraria; Janssen: Honoraria, Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses. Nooka:Adaptive technologies: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; GSK: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Amgen: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation. Moreau:AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Lonial:Janssen: Consultancy, Research Funding; GSK: Consultancy; Karyopharm: Consultancy; BMS: Consultancy; Celgene Corporation: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Genentech: Consultancy. Dimopoulos:Sanofi Oncology: Research Funding. Vij:Takeda: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Tuchman:Prothena: Research Funding; Amgen: Research Funding; Karyopharm: Honoraria; Alnylam: Honoraria, Research Funding; Sanofi: Research Funding; Merck: Research Funding; Roche: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau. Hoffman:Celgene: Speakers Bureau. Costa:Abbvie: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor. Biran:Janssen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Bristol Meyers Squibb: Research Funding; Takeda: Consultancy, Honoraria. Siegel:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Picklesimer:Karyopharm Therapeutics: Employment, Equity Ownership. Saint-Martin:Karyopharm Therapeutics: Employment, Equity Ownership. Li:Karyopharm Therapeutics: Employment, Equity Ownership. Kauffman:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shacham:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Richardson:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Jagannath:Multiple Myeloma Research Foundation: Speakers Bureau; Medicom: Speakers Bureau; Merck: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy.

Abstract: Introduction: Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor plus low dose dexamethasone (Sel-dex) was recently approved in the United States based on data from the STORM study wherein, Sel-dex induced an overall response rate (ORR) of 26.2% in patients with penta-exposed, triple-class refractory multiple myeloma. The presence of high-risk cytogenetic abnormalities is known to have a poor prognosis in multiple myeloma, with transient responses. We performed post-hoc analyses to determine the outcomes in patients with relapsed/refractory myeloma treated with Sel-dex based on the baseline cytogenetic abnormalities. Methods: STORM was a phase 2b, open-label study which enrolled patients with relapsed and refractory myeloma. Selinexor 80 mg in combination with dexamethasone 20 mg was administered orally, twice weekly. The primary endpoint was ORR. For this analysis, we pooled 78 patients (48 quad-refractory and 30 penta-refractory) from STORM, part 1 and 122 patients (penta-exposed and triple class refractory) from STORM, part 2 to compare outcomes between high-risk and standard risk cytogenetics groups. High-risk cytogenetics was defined as having at least 1 of the following abnormalities by fluorescence in-situ hybridization (FISH) at baseline: del(17p), t(4;14), t(14;16), and gain(1q) in 〉 5% of screened plasma cells. The FISH analyses were performed at a central laboratory and used to assess cytogenetic risk status. Results: Of the 200 patients, 122 (61%) had high-risk disease (del(17p): 36%, t(4;14): 18%, t(14;16): 5%, and gain(1q): 36%). The ORR in high-risk patients was 20.5% (very good partial response [VGPR)]: 5.7% and partial response [PR] : 14.8%) and the ORR was 29.5 % (complete response [CR]: 2.6%, VGPR: 3.8%, and PR: 23.1%) in standard-risk patients. The clinical benefit rate (CBR) was 35.2% in high-risk patients compared with 38.5% in standard-risk patients. Median duration of clinical benefit (DOCB) was 4.4 and 6.2 months in the high-risk and standard-risk patients respectively. Median progression-free survival (PFS) was 3.8 and 4.2 months and overall survival (OS) was 8.6 and 9.4 months in the high-risk and standard-risk patients, respectively. Efficacy by specific cytogenetic abnormality is presented in Table 1 below (Due to the small sample size (n=11), data for the t(14;16) subgroup are not presented separately). Conclusions: Sel-dex demonstrated a similar CBR in patients with high risk and standard risk disease and preserved clinical benefit in heavily pre-treated patients who had rapidly proliferative disease and high-risk cytogenetics at baseline. The benefit was maintained across cytogenetic risk subgroups with a higher ORR in the t(4;14) and gain(1q) subgroups. The DOR and OS was similar across all the subgroups. These analyses support the use of Sel-dex in patients with high-risk cytogenetics and warrant further evaluation of selinexor in combination with other anti-myeloma therapies in high-risk disease. Disclosures Nooka: GSK: Honoraria, Other: advisory board participation; Amgen: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation. Yee:Adaptive: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Huff:Karyopharm, Sanofi, MiDiagnostics: Consultancy; Member of Safety Monitoring Board for Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Vogl:Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Active Biotech: Consultancy. Chari:Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Oncoceutics: Research Funding. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; alexion: Consultancy; Janssen: Consultancy. Lonial:Genentech: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; BMS: Consultancy; Janssen: Consultancy, Research Funding; GSK: Consultancy; Celgene Corporation: Consultancy, Research Funding. Dimopoulos:Sanofi Oncology: Research Funding. Vij:Takeda: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Tuchman:Karyopharm: Honoraria; Celgene: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding; Merck: Research Funding; Prothena: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Alnylam: Honoraria, Research Funding. Biran:Bristol Meyers Squibb: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Siegel:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Richardson:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Liu:Karyopharm Therapeutics: Employment, Equity Ownership. Joshi:Karyopharm Therapeutics: Employment, Equity Ownership. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Shacham:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kauffman:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jagannath:Medicom: Speakers Bureau; Multiple Myeloma Research Foundation: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Merck: Consultancy.

Abstract: Introduction: Proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and the CD38 monoclonal antibody daratumumab (dara) have transformed the management of MM, yet eventual refractoriness to these agents seems inevitable. Relapsed and refractory MM (RRMM) which becomes triple class refractory (TCR, i.e. refractory to a PI, an IMiD and Dara) uncommonly responds to further lines of therapy and survival is dismal. Selinexor is a selective inhibitor of nuclear export compound targeting exportin 1 (XPO1) which is overexpressed in MM cells and essential for their survival. In the STORM study, selinexor in combination with low-dose dexamethasone (Sd) demonstrated promising efficacy in TCR, penta-exposed (TCR-PE, i.e. exposed to lenalidomide, pomalidomide, bortezomib, carfilzomib and dara) MM. Establishing the natural history for outcomes in the TCR-PE population can help provide context to understand the outcomes observed with Sd in STORM. In the retrospective MAMMOTH study, we reported the outcomes of patients with RRMM after they became refractory to dara, including a subset of patients who were TCR. We further analyzed the MAMMOTH dataset to generate a cohort of patients similar to patients in STORM in order to compare conventional care vs. Sd. Methods: We included all patients in STORM who received Sd as the first line therapy after they achieved TCR-PE status (n=64). We extracted from the MAMMOTH dataset all patients who were not exposed to Sd in a subsequent line of therapy, became TCR-PE and who received subsequent MM-directed therapy (n=128). Overall response rate (ORR) was evaluated according to IMWG criteria. Overall survival (OS) was calculated from the time of initiation of next line of therapy after TCR-PE status until death or last follow-up. We compared OS in STORM vs. MAMMOTH utilizing cox-regression analysis with adjustment for covariables potentially influencing the outcome. Results: Baseline patient characteristics and prior therapies are per table. The two cohorts were similar in terms of age, number of prior lines of therapy and presence of high-risk cytogenetic abnormalities. STORM patients had longer time between MM diagnosis and post TCR-PE therapy with a higher proportion of refractoriness to carfilzomib. Patients in STORM had ORR to Sd of 32.8% vs 25.0% for patients receiving conventional care in MAMMOTH (P=0.078). In direct comparison, patients in STORM had better OS than patients in MAMMOTH (median 10.4 vs. 6.9 months) (P=0.043, figure). In multivariate analysis, STORM patients had lower risk of death in comparison with MAMMOTH patients (aHR=0.55, 95%C.I. 0.35-0.86, P=0.009). Refractoriness to carfilzomib (aHR=2.20, 95%C.I. 1.16-4.15, P=0.015) and high-risk cytogenetics (aHR-1.66, 95% C.I. 1.13-2.42, P=0.009) were also associated with inferior OS. Conclusion: Despite inherent limitations in comparison of trial enrollees vs. real world patients, this analysis suggests improved OS with Sd vs conventional care in patients with TCR-PE RRMM. Prognosis for these patients remains poor and underscores the need for therapeutic advancements. Disclosures Costa: Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Hari:Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria. Kumar:Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. Tang:Karyopharm: Employment. Shah:Karyopharm Therapeutics Inc: Employment, Equity Ownership. Jagannath:BMS: Consultancy; Merck: Consultancy; Medicom: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy; Multiple Myeloma Research Foundation: Speakers Bureau. Chari:Oncoceutics: Research Funding; Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding. Shacham:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Ma:Karyopharm: Employment, Equity Ownership. Siegel:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Biran:Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol Meyers Squibb: Research Funding. Lonial:BMS: Consultancy; Genentech: Consultancy; GSK: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Celgene Corporation: Consultancy, Research Funding; Karyopharm: Consultancy. Richardson:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Kauffman:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Malek:Adaptive: Consultancy; Amgen: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Medpacto: Research Funding. Fiala:Incyte: Research Funding. Usmani:Amgen, Celgene, Janssen, Sanofi, Takeda: Speakers Bureau; Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, SkylineDX, Takeda: Other: Consultant/Advisor; Amgen Array Biopharma, Bristol-Myers Squibb, Celgene, Janssen, Merck, Pharmacyclics, Sanofi, Takeda: Other: Research Grant. Kang:Takeda Oncology: Consultancy; InCyte Corportation: Research Funding. Cornell:Takeda: Consultancy; KaryoPharm: Consultancy.

Abstract: Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first‐in‐class, once‐daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low‐dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2‐stage design. The primary objective was clinical benefit rate ( CBR ; ≥minimal response); secondary objectives included safety. Patients ( n  =   92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n  =   43), with median duration of 9·2 months (range, 3·0–14·7). Progression‐free survival was 4·6 months (range, 0·4–17·3). Grade 3–4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3–4 non‐haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre‐treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment.

Abstract: To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma. Patients and Methods Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m 2 intravenous bolus on days 1, 4, 8, and 11, every 21 days, for up to eight cycles. Peripheral neuropathy was evaluated at baseline, during the study, and after the study by patient-reported symptoms using the Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire and neurologic examination. During the study, peripheral neuropathy was also evaluated by investigator assessment. A subset of patients underwent nerve conduction studies (n = 13). Results Before treatment, 194 (81%) of 239 patients had peripheral neuropathy by FACT/GOG-Ntx questionnaire, and 203 (83%) of 244 patients had peripheral neuropathy by neurologic examination. Treatment-emergent neuropathy was reported in 35% of patients, including 37% (84 of 228 patients) receiving bortezomib 1.3 mg/m 2 and 21% (six of 28 patients) receiving bortezomib 1.0 mg/m 2 . Grade 1 or 2, 3, and 4 neuropathy occurred in 22%, 13%, and 0.4% of patients, respectively. The incidence of grade ≥ 3 neuropathy was higher among patients with baseline neuropathy by FACT/GOG-Ntx questionnaire compared with patients without baseline neuropathy (14% v 4%, respectively). In all 256 patients, neuropathy led to dose reduction in 12% and discontinuation in 5%. Of 35 patients with neuropathy ≥ grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%. Conclusion Bortezomib-associated peripheral neuropathy seemed reversible in the majority of patients after dose reduction or discontinuation. Although severe neuropathy was more frequent in the presence of baseline neuropathy, the overall occurrence was independent of baseline neuropathy or type of prior therapy.

Abstract: Introduction: IBER is an oral, potent novel cereblon E3 ligase modulator (CELMoD) agent with marked synergistic tumoricidal and immune-stimulatory effects in combination with BORT or DARA in preclinical models. CC-220-MM-001 is a phase 1/2 study evaluating dose escalations of IBER with different treatment combinations in independent cohorts, in patients (pts) with RRMM (NCT02773030); the IBER + DEX cohort showed a favorable safety profile with promising efficacy and a selected IBER RP2D of 1.6 mg 21/28 days (D). Here, we present results from the IBER + DARA + DEX (IberDd) and IBER + BORT + DEX (IberVd) cohorts. Methods: Eligible pts had received ≥ 2 prior regimens in the IberDd cohort, and ≥ 1 prior regimen in the IberVd cohort, containing at least lenalidomide or pomalidomide, and a proteasome inhibitor (PI), and had experienced disease progression on or within 60 days of last MM therapy. Escalating doses of IBER were given orally, in the IberDd cohort on D1-21, with DARA (16 mg/kg) on D1, D8, D15, and D22 (cycles [C]1-2), D1 and D15 (C3-6), and D1 (C ≥ 7), of each 28-day cycle; in the IberVd cohort, on D1-14, with BORT (1.3 mg/m2) on D1, D4, D8, and D11 (C1-8), and on D1 and D8 (C ≥ 9), of each 21-day cycle. In both cohorts DEX was given weekly. Primary objectives were to evaluate MTD, RP2D, and safety separately for each cohort; a key secondary objective was preliminary assessment of efficacy. Immune profiling was evaluated by flow cytometry from pt peripheral blood at C1D1, C2D15, C4D1, and C4D15. Results: As of June 18, 2020, 19 pts had received IberDd and 21 pts IberVd. Baseline characteristics for the 2 independent cohorts are shown in the table. All pts were refractory to their last prior regimen, and exposure to prior regimens was heterogeneous. IBER doses ranged from 1.0 to 1.6 mg; the MTD/RP2D has not been reached in either cohort. Median follow-up was 5 (0-14) and 3 (0-11) months, 10 (53%) and 13 (62%) pts continue on treatment, median cycles received was 5 (1-14) and 4.5 (1-17), with IberDd and IberVd, respectively. Grade (Gr) 3-4 treatment-emergent adverse events (TEAEs) were reported in 14 (78%) pts with IberDd, and in 13 (65%) pts with IberVd. Most frequent Gr 3-4 TEAEs of interest included neutropenia (50%), leukopenia (22%), and anemia (22%) with IberDd; and neutropenia (20%) and thrombocytopenia (20%) with IberVd. In both cohorts, neutropenia was managed with G-CSF. One pt (IberDd; 1.2 mg dose) had Gr 4 neutropenic sepsis. Occurrence of Gr 3-4 non-hematological TEAEs was low in both cohorts. One pt had Gr 2 infusion-related reaction with IberDd, and 3 pts had Gr 1-2 peripheral neuropathy with IberVd. Six (33%) and 4 (20%) pts had IBER dose reductions with IberDd and IberVd, respectively. In the IberDd cohort, with 12/19 (63%) DARA-refractory pts and 11 (58%) quad-class-refractory pts, the overall response rate (ORR) was 35% across all dosing groups (2 very good partial responses [VGPRs], 4 partial responses [PRs] ); the clinical benefit rate (CBR) was 47% and disease control rate (DCR) was 88%. In the IberVd cohort, with 16/21 (76%) PI-refractory pts, 9 (43%) BORT-refractory pts, and 10 (48%) quad-class refractory pts, ORR was 50% (1 complete response, 3 VGPRs, 6 PRs); CBR was 65% and DCR was 85%. Responses with IberDd and IberVd were observed irrespective of DARA- and BORT-refractoriness, respectively. Median time to response was 4.1 (4.1-12.0) and 4.9 (3.0-13.1) weeks, in the IberDd and IberVd cohorts, respectively; median duration of response was not reached in both cohorts. Immune profiling showed dose-dependent decreases in B cells and increases in activated and differentiated T cells, in both cohorts. Except for reductions in CD38+ T cells in pts receiving IberDd, these observations were similar in pts treated with IBER + DEX. Conclusions: IberDd and IberVd showed a favorable tolerability profile in heavily pretreated RRMM pts, with promising clinical activity, even among pts refractory to the last prior regimen and previously exposed to IMiD agents, PIs, and CD38 antibodies. Immune-profiling data confirm that IBER + DEX was pharmacodynamically active in triplet combination and not augmented by the addition of DARA or BORT. The study is ongoing with continued enrollment at the 1.6 mg dose level for both cohorts. Updated results, including the MTD/RP2D, will be presented at the meeting. These results support the further development of IBER-based regimens in MM; phase 3 trials are planned to further evaluate these combinations. Disclosures van de Donk: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Ferrer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Popat:Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Minnema:Servier: Consultancy; Kite, a Gilead Company: Speakers Bureau; Celgene: Other: travel support, Research Funding; Amgen: Consultancy. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Oriol:Sanofi: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Zonder:Prothena: Consultancy; Intellia: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Research Funding; BMS: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Oncopeptide: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Alnylam: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Other: Personal fees; Caelum: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Rodriguez-Otero:Sanofi: Consultancy, Honoraria; Medscape: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company, Honoraria; Abbvie: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Stadtmauer:Sanofi: Consultancy; AbbVie: Research Funding; Takeda: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding. Bringhen:Bristol-Myers Squibb: Honoraria; Amgen: 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; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Siegel:Takeda: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celulatiry: Consultancy; Karyopharma: Consultancy, Honoraria. Gamberi:Janssen: Consultancy, Honoraria; GSK: Consultancy; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Gironella Mesa:Janssen: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria, Speakers Bureau. Sonneveld:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Skyline Dx: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy. Nguyen:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Di Micco:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Sorrell:Children's Oncology Group: Other: Non-member; Previous Study Chair AAML08B1; Bristol Myers Squibb: Current Employment. Chen:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Amatangelo:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Kueenburg:Celgene International Sàrl, a Bristol Myers Squibb Company, Boudry, Switzerland: Current Employment. Lonial:Onyx: Honoraria; Novartis: Consultancy, Honoraria, Other: Personal fees; Genentech: Consultancy; Amgen: Consultancy, Honoraria, Other: Personal fees; Merck: Consultancy, Honoraria, Other: Personal fees; Abbvie: Consultancy; Millennium: Consultancy, Honoraria; Karyopharm: Consultancy; Sanofi: Consultancy; JUNO Therapeutics: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Other: Personal fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding; GSK: Consultancy, Honoraria, Other: Personal fees.

Abstract: Abstract 450 Background: New antimyeloma treatments that re-establish tumor response are required to improve survival for pts with advanced, treatment-refractory MM. The MM-002 phase 2 study evaluated the safety and efficacy of oral pomalidomide, in combination with low-dose dexamethasone (POM+LoDex), in pts with relapsed and refractory multiple myeloma (RRMM) who have who have received ≥2 prior therapies including LEN and BORT (Richardson PG, et al. Blood 2011;118:abs 634). Updated results from March 2012 for pts and the outcomes of subgroup analyses are presented. Methods: Eligible pts with MM who had received at least 2 prior therapies (including LEN and BORT) and had disease progression within 60 days of their last treatment were randomized (1:1 ratio) to either POM+LoDEX (POM, 4 mg/day for days 1–21 of a 28-day cycle; LoDex, 40 mg/week) or POM alone. At progression, pts receiving POM alone could receive POM+LoDEX at investigator's discretion. Pts aged over 75 years received LoDex, 20 mg/week. All pts received mandatory thromboprophylaxis (daily low-dose aspirin). Pts were stratified within each treatment group according to age. The key efficacy endpoints included the objective response rate using European Bone Marrow Transplantation (EBMT) criteria, duration of response, progression free survival (PFS) and overall survival (OS), and safety. This updated analysis focused on pts on the POM+LoDex arm. Results: The intention-to-treat efficacy analysis included 113 pts in the POM+LoDex group. The mean age of pts treated with POM+LoDex was 64 years (range, 34–88); 99 pts (88%) were aged ≤75 years. Response rates, median duration of response, and age subgroups are presented in the Table. Median PFS and OS were 4.6 months (mos) and 16.5 mos, respectively, in the POM+LoDex group overall. In the age subgroup analysis of pts treated with POM+LoDex, the median PFS was 4.7 mos in pts aged ≤65 years, and 3.7 mos in pts 〉 65 years. Median OS was 19.7 mos in pts aged ≤65 years and 11.8 mos in pts 〉 65 years. The most common grade 3 or 4 adverse events (AEs) occurring in 〉 5% of pts were neutropenia (41%), anemia (22%), pneumonia (22%), thrombocytopenia (19%), fatigue (14%), dyspnea (13%), leukopenia (10%), back pain (10%), and urinary tract infection (9%). AEs led to at least one dose reduction in 26% of pts; neutropenia was associated with a dose reduction in 4% of pts. Overall, 78% of pts who developed grade 3 or 4 neutropenia used G-CSF during study treatment. There were no reports of grade 3 or 4 peripheral neuropathy (PN); grade 1 or 2 PN occurred in 7% of pts treated with POM+LoDex. Deep vein thrombosis (any grade) occurred in 2 pts (2%), both aged ≤65 years. Grade 3 or 4 neutropenia occurred in 46% of pts aged ≤65 years and in 35% of pts aged 〉 65 years. Despite this, only 1 pt in each age group developed febrile neutropenia (2%). The mean relative dose intensity (dose intensity/planned dose intensity) was 0.9 in both pt groups of ≤65 years and 〉 65 years receiving POM+LoDex. Overall, 21 pts (19%) of the POM+LoDex group died during the study. The most common cause of death was progressive MM (52%; only in 14% of all cases was it due to disease progression); other causes of death (48%) included infections, cerebral/intracranial/subarachonoid hemorrhage, acute respiratory distress syndrome, and suicide in one pt with a history of severe depression. Conclusions: POM, 4 mg/day for days 1–21 of a 28-day cycle in combination with LoDex, is clinically effective and generally well tolerated in pts with RRMM who have received multiple prior treatments including LEN and BORT. POM+LoDex represents an important potential new treatment option for pts with advanced MM and appears active in both younger and older pts, with tolerability similar across different age groups. Phase 3 studies of POM+LoDEX in combination with other agents (e.g. bortezomib) are ongoing. Disclosures: Jagannath: Millennium Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Pomalidomide is an investigational drug and is not approved for the treatment of patients with any condition. Hofmeister:Celgene: Advisory Board Other, Honoraria. Siegel:Onyx: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Millennium Pharma: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Celgene: Advisory Board Other, Honoraria, Speakers Bureau; Merck: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau. Vij:Onyx: Consultancy, Research Funding; Millennium Pharma: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Lonial:Millennium, Celgene, Novartis, BMS, Onyx, Merck; all 〈 $10,000 per year and disclosed to my institution: Consultancy. Anderson:Acetylon, Oncopep: Scientific Founder, Scientific Founder Other; Celgene, Millennium, BMS, Onyx: Membership on an entity's Board of Directors or advisory committees. Chen:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Richardson:Celgene, Millennium, Johnson & Johnson: Advisory Board Other.

Abstract: Introduction: Multiple myeloma (MM) remains an incurable disease in need of new therapies with unique targets. Ibrutinib is a first-in-class, once-daily, oral, covalent inhibitor of Bruton’s tyrosine kinase (BTK), an essential enzyme in the B-cell receptor signaling pathway. While BTK is essential for the development and function of B cells and is down-regulated in plasma cells, the expression of BTK in malignant plasma cells is increased 4-fold and comparable to BTK expression levels in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In addition, pre-clinical models show that BTK inhibition with ibrutinib led to direct inhibition of both osteoclast bone resorption and the release of osteoclast-derived tumor growth factors (Tai et al, Blood 2012). Taken together these data suggest that ibrutinib may have a role in the treatment of MM. Methods: This open label phase 2 dose escalation study was designed to enroll patients in 4 cohorts (Figure) to evaluate efficacy (≥MR) and secondary endpoints of safety, PK, ORR and DOR. Patients must have had documented non-responsive/progressive disease at the time of study entry following at least 2 prior lines of therapy including at least one immunomodulatory agent. Efficacy and safety were assessed at 4 weeks intervals using the IMWG response criteria for efficacy assessments (Rajkumar et al, Blood 2011), while safety was assessed according to CTCAE v4.0 criteria. Results: As of 15 May 2014 and a median follow up of 15.2 months, 69 patients with a median age of 64 years (range 43-81) were dosed, of which 20% had either a del 17p or p53 deletion. The number of median prior therapies was 4 (range, 2-14), 41% had ≥ 5 prior therapies and 80% had undergone autologous stem cell transplant. Sixty-two percent of patients were refractory to their last line of therapy and of the 65 patients that had received prior therapy with both an immunomodulatory agent and a proteasome inhibitor, 44% were refractory to both. Anti-tumor activity was noted across all cohorts. The highest activity with a clinical benefit rate (CBR) of 25% including 1 PR, 4 MR and 5 sustained ( 〉 4 cycles) SD was observed in Cohort 4. (Table) This led to expansion of Cohort 4 per protocol design. In Cohorts 1 and 3, 14 patients had dex added following PD, resulting in 1 PR and 9 SD. Overall, 57% experienced a Grade 3 or higher adverse event. The most commonly reported non-hematologic toxicities (any grade) were diarrhea (51%), fatigue (41%), nausea (35%), dizziness (25%), and muscle spasms (23%). The majority were Grade 1 and 2. Myelosuppression had a reported overall incidence of any grade anemia (29%), thrombocytopenia (23%), and neutropenia (7%) with 16%, 9% and 4% being Grade 3, respectively. There were no clinically meaningful differences among dose levels. Twenty-three patients experienced a SAE for a total of 47 reported events with 16 assessed as possibly/definitely related to ibrutinib per investigator. At least one dose modification occurred in 22% of patients, with 6 discontinuing due to an adverse event. At the time of the data cut-off 7 patients remain on study treatment. The most common reason for treatment discontinuation was PD in 47% of patients, with additional patients discontinuing due to investigator discretion (18%), patient decision (7%) and non-compliance (3%). Conclusions: In this heavily pre-treated patient population ibrutinib, as a single agent and in combination with dex, demonstrated evidence of anti-tumor activity. There was a trend toward improved efficacy (≥MR) in Cohort 4 and treatment was well tolerated with manageable toxicities. Ongoing correlative studies are being conducted to determine changes in cytokines, chemokines and indices of bone metabolism and to determine the effect of dex, a known CYP3A4/5 inducer, on the pharmacokinetic profile of ibrutinib. In addition, ibrutinib is currently being evaluated in combination with carfilzomib in an ongoing Phase1/2b study. (NCT01962792) Figure 1 Figure 1. Table Confirmed Response by Assigned Treatment Cohort Response, n (%) 1 (n=13) 2 (n=18) 3 (n=18) 4 (n=20) PR 1 1 - 1 MR 1 - - 4 SD ≥ 4 cycles 2 4 6 5 SD 〈 4 cycles 5 6 4 1 PD 4 5 7 5 Not evaluable - 2 1 4 Not evaluable – no post-baseline assessments Figure 2 Figure 2. Disclosures Off Label Use: Discussion of efficacy and safety data with ibrutinib as single-agent and in combination with dexamethasone in patients with relapsed and relapsed/refractory multiple myeloma treated in a phase 2 clinical trial. Huff:Celgene, Millenium: Consultancy. Bensinger:Pharmacyclics, Novartis, Celgene, Millenium, Sanofi, Acetylon: Consultancy, Research Funding. Siegel:Celgene, Millennium, Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jagannath:Celgene, BMS, Jansen, Sanofi-Aventis: Honoraria. Lebovic:Onyx, Celgene: Speakers Bureau. Anderson:Celgene, Millenium, Onyx, : Speakers Bureau. Elias:Pharmacyclics, Inc.: Employment. Clow:Pharmacyclics, Inc.: Employment. Fardis:Pharmacyclics: Employment. Graef:Pharmacyclics: Employment. Bilotti:Pharmacyclics: Employment. Richardson:Celgene, Millennium, Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees.

Abstract: Pomalidomide plus low-dose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma. Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.