ALBERT

Description: Background: Histone acetylation plays a key role in regulating gene expression and in control of cellular activities in multiple pathways involved in normal and cancer cell growth.Panobinostat (pano) is a pan histone de-acetylase inhibitor (HDAC-i) approved by the FDA on February 23, 2015 for use withbortezomib (btz) and dexamethasone (dex) for patients with multiple myeloma (MM) who have had at least 2 prior lines of therapy including bothbtz and an immunomodulatory agent (IMiD). The combination ofpano withIMiDs and proteasome inhibitors (PIs) has been found to demonstrate enhanced anti-myeloma activity in clinical trials (Berdeja JG et al, 2015,Haematologica;Mateos M et al, 2010, ASCO Abstract 8030, JCO 28:15s). The goal of this retrospective study is to evaluate the real world experience on efficacy and safety ofpano in combination with a variety of FDA approved agents including a PI, anIMiD or a monoclonal antibody-based regimen in patients with relapsed/refractory MM. Methods: Between February 23, 2015 and July 1, 2016, 34 consecutive patients with relapsed/refractory MM who were treated with commercialpano were identified from the JohnTheurer Cancer Center. Charts were analyzed for response and safety data. The study was approved by the institutional review board. Results: Median age was 63 (range 27-78), with 58% percent men. Thirty-one patients (91.2%) wereDurie-Salmon stage II or III. Ten (30%) had high-risk FISH as defined byt(14;16), t(4;14), del p53, and gain 1q21. Median number of prior lines was 5 (range 2-9). All patients were relapsed/refractory to their last line of therapy, and 18 (53%) werebtz-refractory, 25 (74%) werelenalidomide-refractory, 27 (79%) werepomalidomide-refractory, and 29 (85%) were carfilzomib-refractory. Twenty-five (74%) were refractory to the combination of carfilzomib with anIMiD. Five patients (14.7%) had priordaratumumab, and 4 (12%) had prior HDAC-i therapy. Median number of cycles withpano was 1 (range 1-5). The overall response rate (≥ partial response (PR)) was 23.5% and the clinical benefit rate (≥ minor response (MR)) was 67.6%. The median duration of response (≥ stable disease (SD)) was 3 months. The median progression-free survival (PFS) for all patients was 2.3 months (95% CI: [1.27 - 4.07]). See Figure 1. Median overall survival (OS) from initiation ofpano through 7/27/16 was 5.5 months (95% CI: [3.93, NA]). See Figure 2. Of the 4 patients who were refractory to a prior HDAC-i, 1 achieved PR (4 cycles), 1 achieved MR (5 cycles) and 2 had disease progression. Only 1 patient discontinuedpano due to toxicities. Grade 3 and 4 non-hematologic toxicities were diarrhea (N=1), and hypoxia/respiratory failure (N=1). Grade 3 and 4 hematologic toxicities occurred in 11 (32%) patients, with 5 (15%) anemia, 9 neutropenia (26%), and 8 (24%) thrombocytopenia. Serious adverse events included acute kidney injury, GI bleed, and febrile neutropenia in 3 patients, respectively. Conclusions: These observations demonstrate that real-world use ofpano outside of the FDA indication in combination with PI andIMiD-based regimens has activity and is well tolerated in heavily pretreated patients with relapsed/refractory MM, even those who have exhausted conventional treatments. Further assessment in a larger prospective study is warranted. Figure 1 PFS of all patients receivingpanobinostat-based regimens Figure 1. PFS of all patients receivingpanobinostat-based regimens Figure 2 OS of all patients receivingpanobinostat-based regimens from time of initiatingpanobinostat Figure 2. OS of all patients receivingpanobinostat-based regimens from time of initiatingpanobinostat Disclosures Biran: Takeda: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau. Vesole:Janssen: Speakers Bureau; Novartis: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau. Richter:Celgene: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Jannsen: Speakers Bureau. Siegel:Celgene: Honoraria, Speakers Bureau; Merck: Honoraria; Takeda: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau.

Description: Key Points Presented are results from the phase 2 dose-expansion study of the combination of carfilzomib, lenalidomide, and dexamethasone (CRd). CRd was well tolerated with robust, rapid, and durable responses.

Description: Background: The discovery that gut microbial dysbiosis correlated with prognosis, immune reconstitution and development of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplantation (allo-SCT) highlights the clinical relevance of the gut microbiome in shaping anti-tumor immune responses. Treatment of allo-SCT patients with antibiotics has recently been associated with increased GVHD mortality (Routy et al. 2017). Based on these studies and the association of distinct gut bacteria with increased efficacy to PD-1 blockade in patients with solid tumors (Derosa et al. 2018), we performed a retrospective analysis to determine if infection treated with antibiotics affected the outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: A list of all MM patients treated at our institution between January 2012 through December 2015 was obtained and 1095 patients were identified. A comprehensive review of the electronic medical record (EMR) of the first 142 who received ASCT was performed. Information was collected from diagnosis to the date of last contact. Baseline characteristics, treatment history, transplant course, antibiotic treatment, and infection severity using common terminology criteria for adverse event (CTCAE) version 4 were reviewed. Prophylactic antibiotics were excluded. Response was measured and defined using the International Myeloma Working Group Criteria. Progression free survival (PFS) and overall survival (OS) were estimated using log rank tests. Cox hazard stepwise regression model examined for multiple factors affecting PFS and OS using the Akaike information criterion. Results: Of the 142 patients, 93 (65%) were Durie Salmon (DS) III, 20 (14%) were Revised International Staging System (R-ISS) III, 44 (31%) had high-risk cytogenetics, and 76 (54%) were male. The median age at diagnosis was 60. Although there was a similar frequency of DS III (67% vs 61%) and high-risk cytogenetics (35% vs 25%) among patients in the antibiotic and non-antibiotic treated groups, there was an over-representation of R-ISS 3 (19% v 4%) patients in the antibiotic-treated group. Treatment with antibiotics was associated with decreased median PFS (2.38 vs 6.58 years (yrs), p =0.00003) (Figure 1a) and decreased median OS (7.43 vs 17.39 yrs, p =

Description: Key Points 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.

Description: Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m2 for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m2 for cycle 1 and then 27 mg/m2 for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy—17.1% overall (1 grade 3; no grade 4)—in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816.

Description: Abstract 3986 Background: Multiple Myeloma (MM) is an incurable plasma cell neoplasm. Although current lenalidomide (R) and bortezomib containing up-front regimens can now achieve overall response rates approaching 100%, patients eventually relapse with progressively refractory disease. Histone deacetylase inhibitors (HDACi), in Phase I clinical trials in patients with multiple myeloma, have shown promising activity when combined with other agents such as bortezomib. Vorinostat, (suberoylanilide hydroxamic acid; SAHA) is an oral HDACi, currently FDA approved in the United States for the treatment of cutaneous T-cell lymphoma. Here we report the findings of the combination of vorinostat (Zolinza®), lenalidomide and dexamethasone (ZRD) in multiple myeloma patients who were refractory to RD. Methods: Patients received oral vorinostat 300 mg or 400 mg once daily (days 1–7 and days 15–21), lenalidomide 10–25 mg (days 1–21) and dexamethasone 20–40 mg weekly (days 1, 8, 15, 22) in a 28-day cycle Subjects: Twenty-nine patients were treated and all were refractory to RD; 76% were refractory to at least one bortezomib containing regimen and 48% were refractory to the combination of VRD. Twenty-six patients (90%) had undergone prior high dose therapy with autologous stem cell transplant. The median number of prior therapies was 4 (range 2–13). Results: The overall response rate (ORR) was 24 % with 1 VGPR and 6 PR. The clinical benefit rate (ORR + MR) was 51% including 8 MR. Nine patients (31%) had stable disease. The median duration of response (DOR) was 4 months (range, 0–36). The median overall survival (OS) was 11 months (range, 4–36). Common toxicities including diarrhea and fatigue (all grades) were 41% and 34% respectively. The incidence of grade 3/4 neutropenia was 45 % and grade 3/4 thrombocytopenia was 34%. Conclusion: The combination of ZRD showed significant activity in patients with RD relapsed/refractory multiple myeloma. ZRD was well tolerated and is a viable option for patients who do not respond to lenalidomide-based therapy. Further, since all 3 agents are available in oral formulations, ZRD provides an additional option for those patients wishing to avoid intravenous therapy. Formal phase II studies of this combination are in preparation. Disclosures: Off Label Use: Vorinostat is an oral HDAC inhibitor and is being evaluated in the treatment of Multiple Myeloma. Bilotti:Celgene: Consultancy, Speakers Bureau; Millenium: Consultancy, Speakers Bureau. McNeill:Celgene: Consultancy, Speakers Bureau; Millenium: Consultancy, Speakers Bureau. Graef:Merck: Employment. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Speakers Bureau. Siegel:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millenium: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck: Consultancy.

Description: Introduction: Continuous treatment with lenalidomide (len) is a new standard of care in frontline multiple myeloma (MM) (Facon. Blood. 2018;131:301-310; Pulte. Oncologist. 2018;23:734-739). The increased adoption of continuous len treatment and len maintenance highlights the need for active regimens for the treatment of MM that has relapsed or become refractory to len. Once-weekly carfilzomib (K) at 70 mg/m2 (Berenson. Blood. 2016;127:3360-3368; Moreau. Lancet Oncol. 2018;19:953-964) and twice-weekly K at 56 mg/m2 (Dimopoulos. Lancet Oncol. 2016;17:27-38) in combination with low-dose dexamethasone (d) have shown a favorable benefit-risk profile for the treatment of relapsed and/or refractory MM. This post-hoc analysis will assess the efficacy and safety of Kd in len exposed and refractory MM. Methods: Individual patient data from the phase 1/2 CHAMPION-1 (CH-1), phase 3 ENDEAVOR, and phase 3 ARROW studies were pooled to evaluate progression-free survival (PFS), overall response rate (ORR), and safety for those with previous exposure or refractoriness to len treatment. The once-weekly Kd dosing schedule in CH-1 (Berenson. Blood. 2016;127:3360-3368) and ARROW (Moreau. Lancet Oncol. 2018;19:953-964) and the twice-weekly Kd dosing schedule in ENDEAVOR (Dimopoulos. Lancet Oncol. 2016;17:27-38) have been previously described. Patients who received once-weekly Kd at 70 mg/m2 in CH-1 and ARROW, and patients who received twice-weekly Kd at 56 mg/m2 from ENDEAVOR were included in the analysis. Patients were assigned to a group according to prior lines of therapy and previous len exposure: (1) combined CH-1 and ENDEAVOR patient population (N=39) that had received 1 prior line of therapy and was previously exposed but not refractory to len (Kd, 1 prior len exposed); (2) combined CH-1 and ENDEAVOR patient population (N=32) that had received 1 prior line of therapy and was refractory to len in the last line of therapy (Kd, 1 prior len refractory); (3) combined CH-1, ENDEAVOR, and ARROW patient population (N=65) that had received 2 to 3 prior lines of therapy and was exposed but not refractory to len (Kd, 〉1 prior len exposed); (4) combined CH-1, ENDEAVOR, and ARROW patient population (N=304) that had received 2 to 3 prior lines of therapy and was refractory to len in any line of previous therapy (Kd, 〉1 prior len refractory). Results: PFS, ORR, and safety outcomes in the pooled len exposed and refractory patient populations are shown (Table 1). Len-exposed patients treated with Kd in first relapse had a median PFS of 18.3 months (95% confidence interval [CI] 14.1-21.0); PFS rate at 18 months was 54.0%. When len-refractory patients were treated with Kd in first relapse, median PFS was 15.6 months (95% CI 9.6-not estimable [NE]) and the PFS rate at 18 months was 43.1%. For len-exposed patients treated in second or third relapse, the median PFS for Kd was not reached (95% CI 10.3-NE) and PFS rate at 18 months was 57.1%. For len-refractory patients treated with Kd in second or third relapse, median PFS was 8.8 months (95% CI 7.5-11.2) and the PFS rate at 18 months was 27.8%. ORR was approximately 90% (Kd, 1 prior len exposed), 81% (Kd, 1 prior len refractory group), 77% (Kd, 〉1 prior len exposed), and 61% (Kd, 〉1 prior len refractory). Median K treatment duration (range) was 56.0 (4.0-213.0) months (Kd, 1 prior len exposed), 36.6 (1.0-201.1) months (Kd, 1 prior len refractory), 36.1 (1.1-210.7) months (Kd, 〉1 prior len exposed), and 34.0 (0.1-198.0) months (Kd, 〉1 prior len refractory). The incidence of treatment-emergent grade ≥3 adverse events (AEs) was 84.6% for patients in the Kd, 1 prior len-exposed group, 81.3% for patients in the Kd, 1 prior len-refractory group, 76.9% for patients in the Kd, 〉1 prior len-exposed group, and 74.8% for patients in the Kd, 〉1 prior len-refractory group. The rate of serious AEs in each of the pooled patient groups in this analysis is presented (Table 1). Conclusion: The Kd doublet is effective and safe in MM patients relapsing on or after treatment with len, and for patients who are refractory to len. Although data are limited by small sample size, the median PFS of 15.6 months for Kd in len-refractory patients treated in first relapse is similar in magnitude to the median PFS reported for novel triplet therapy in this population. Disclosures Mateos: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Berdeja:Genentech: Research Funding; Bluebird: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Teva: Research Funding; Sanofi: Research Funding; Poseida Therapeutics, Inc.: Research Funding. Dimopoulos:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Siegel:Takeda: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Ho:Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Other: travel to meeting; Celgene: Other: travel to meeting. Huang:Amgen: Employment, Equity Ownership. Sersch:Amgen: Employment. Zahlten-Kumeli:Amgen: Employment, Equity Ownership. Kimball:Amgen: Employment, Equity Ownership; WindMIL Therapeutics: Equity Ownership. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding.

Description: Introduction: The randomized phase 3 ENDEAVOR trial demonstrated superior progression-free survival (PFS), overall survival (OS), and health-related quality of life in patients with relapsed or refractory multiple myeloma (RRMM) for patients treated with carfilzomib (56 mg/m2) and dexamethasone (Kd56) compared with bortezomib and dexamethasone (Vd). In patients with relapsed MM, the time of therapy initiation might impact treatment outcome. Prior studies have demonstrated a median of 5 months between the presence of biochemical and symptomatic relapse (Lopez. Leuk Res Rep. 2015;4:64-69). Herein, we report a post hoc subgroup analysis from the ENDEAVOR study to evaluate the impact of initiating Kd56 therapy upon biochemical relapse. Methods: Adults with RRMM who previously received 1-3 lines of therapy and had measurable disease were eligible to participate in the ENDEAVOR trial. Symptomatic disease was not required for eligibility. Kd56 patients received carfilzomib on days 1, 2, 8, 9, 15, and 16 as a 30-minute intravenous infusion and dexamethasone (20 mg) on days 1, 2, 8, 9, 15, 16, 22, and 23 of a 28-day cycle. Vd patients received bortezomib (1.3 mg/m2; intravenous bolus or subcutaneous injection) on days 1, 4, 8 and 11 and dexamethasone (20 mg) on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21-day cycle. Treatment continued until disease progression, physician decision, unacceptable toxicity, withdrawal of consent, or death. This post hoc subgroup analysis evaluated PFS, OS, and safety in subgroups defined according to the presence of symptoms at the time of enrollment. Patients with RRMM who experienced biochemical progression without CRAB symptoms (hypercalcemia, renal impairment, anemia, or bone lesions) upon relapse were considered asymptomatic, whereas symptomatic patients were those who had CRAB symptoms upon relapse. In each subgroup, PFS and OS were compared between treatment arms using an unstratified Cox proportional hazards model. Results: Of the 929 patients enrolled and randomized in ENDEAVOR, 117 (12.6%) were asymptomatic (Kd56, n=60; Vd, n=57) and 812 (87.4%) were symptomatic (Kd56, n=404; Vd, n=408). In the asymptomatic group, the median PFS was not estimable (NE) for Kd56 vs 13.7 months for Vd (hazard ratio [HR]: 0.462; 95% confidence interval [CI]: 0.232-0.922), and the median OS was NE for either treatment arm (HR: 0.768; 95% CI: 0.350-1.683) (Table). In the symptomatic group, median PFS was 17.7 months for Kd56 vs 8.8 months for Vd (HR: 0.539; 95% CI: 0.439-0.662), and median OS was 44.0 months for Kd56 vs. 36.8 months for Vd (HR: 0.801; 95% CI: 0.653-0.982) (Table). Kaplan-Meier PFS and OS curves are shown in the Figure. The rate of grade ≥3 treatment-emergent adverse events (Kd56 vs Vd) was 78.3% vs 58.9% in the asymptomatic group and 81.9% vs 72.8% in the symptomatic group (Table). Conclusions: Kd56 demonstrated superior survival outcomes compared with Vd in patients with RRMM, regardless of presence of CRAB symptoms at study randomization. As expected, outcomes were improved when Kd56 was initiated early in the disease course, before CRAB symptoms occurred. The small size of the subgroups in this study is a limitation. However, the findings warrant further investigation. The safety profile of Kd56 in both subgroups was consistent with that in the overall population as previously reported (Dimopoulos. Lancet Oncol. 2016;17:27-38; Siegel, Clin Lymphoma Myeloma Leuk. 2017;17:e142). Overall, Kd56 had a favorable benefit-risk profile in both patients with biochemical and symptomatic relapse. Disclosures Moreau: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: 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; Janssen: 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. Siegel:Merck: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Goldschmidt:Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; ArtTempi: Honoraria; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Mundipharma: Research Funding; Adaptive Biotechnology: Consultancy; Amgen: Consultancy, Research Funding. Niesvizky:Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Amgen Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Bringhen:Takeda: Consultancy; Janssen: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria. Orlowski:Spectrum Pharma: Research Funding; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Sanofi-Aventis: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Kite Pharma: Consultancy. Blaedel:Amgen: Employment, Equity Ownership. Yang:Amgen Inc.: Employment, Equity Ownership. Dimopoulos:Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria.

Description: Abstract 3989 Background: Treatment patterns of multiple myeloma (MM) vary across the globe, mostly dictated by the availability and patient access to different drug therapies. The outcomes of patients with MM, especially relapsed myeloma can be significantly affected by the availability of newer treatments, as well as potential biological differences related to ethnicity. We have previously shown that the outcome of patients relapsing after therapy with bortezomib (Bz) and one or more of the IMiDs remain poor with the currently available treatments and represent a difficult group of patients to treat. We undertook the current analysis on a set of patients from United States, several European countries and South Korea. Methods: We designed a multicenter, retrospective study that enrolled 294 patients with relapsed MM, from 14 sites (122 from Europe, 107 from US, and 65 from Korea). Patients were refractory to Bz, defined as no response to prior Bz-containing regimen or disease progression within 60 days of a Bz-containing regimen. Patients were also relapsed, refractory, intolerant, and/or ineligible, to treatment with an IMiD (thalidomide or lenalidomide). The date patients satisfied the above entry criteria was defined as time zero (T0). Clinical and laboratory data from diagnosis and individual relapses were collected along with details of all MM drug therapies before and after T0. Responses were assessed by IMWG or EBMT criteria. The goal of the study was to compare the characteristics of patients who satisfy the above inclusion criteria, the therapies employed prior to and after T0 and clinical outcome among these patients from different parts of the world. Results: The mean (median, range) time to reaching T0 from diagnosis was 4.5 (4.0, 12.8), 4.2 (3.2, 18.6), and 3.2 (2.8, 9.6) years from diagnosis for patients from US, Europe and Korea, respectively, P=0.021. The mean (median, range) number of therapies for the three groups were 8 (8, 13), 4 (4, 10), 5 (4, 7), respectively; P=PR) to the initial therapy at diagnosis were 56%, 77% and 49% respectively for the US, European and Korean cohorts. Overall 220 patients had at least one therapy after T0, and 114 (52%) had a novel agent (Bz, len or thal) containing regimen as their first treatment after T0. Patients in US were more likely to receive additional therapies after the first post-T0 therapy; 62%, 32%, and 12% of patients from US, Europe and Korea, respectively, began a second post-T0 regimen within 2 years following time zero. The median number of therapies post T0 was 2, 1, and 1 for patients in US, Europe and Korea respectively. The response rates to the first regimen after T0 were 15%, 33% and 19% for the US, European and Korean cohorts, and were similar between those receiving a regimen with one of the novel drugs compared to rest. Patients younger than 60 years and those with prior transplants were more likely to respond to post T0 regimens. The median time to progression or death from T0was similar for the three patient cohorts, 5 months (Figure 1A). The median overall survival (95% CI) from T0 was 13 months (10, 16), 7 (5,9) and 8 (4,9) respectively for the US, European and Korean cohorts (Figure 1B). Conventional prognostic factors, especially the ISS stage was predictive of OS post T0. Additionally, presence of extramedullary disease was associated with a shorter overall survival. Conclusion: The results of the current study demonstrate significant differences between different parts of the world in terms of the treatment patterns both in the setting of initial therapy as well as treatment of relapsed disease. Patients in the US were more likely to receive multiple regimens both before and after T0. This is likely a reflection of increasing numbers of new drugs that have gone into clinical trials and thus enhancing options. The study further highlights the poor outcome of patients who have relapsed after the new drugs, irrespective of the geographical location. Disclosures: Kumar: Merck: Consultancy, Honoraria; Genzyme: Consultancy; Celgene: Consultancy. Richardson:Millennium: ; Celgene: ; Johnson & Johnson: ; Novartis: ; Bristol Myers Squibb:. Moreau:Millennium Pharmaceuticals, Inc.: Advisory board, Honoraria; Janssen: Advisory board, Honoraria. Sonneveld:Millennium Pharmaceuticals, Inc.: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding. Siegel:Merck: Honoraria; Millenium: Honoraria, Research Funding, Speakers Bureau. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palumbo:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Durie:Celgene: Membership on an entity's Board of Directors or advisory committees.

Description: 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.