Roy, Vivek

Abstract Abstract 3854 Poster Board III-790 Background Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, has been shown to be active in patients with multiple myeloma. Pomalidomide is a derivative of thalidomide that acts as an immunomodulator. Preliminary data in multiple myeloma demonstrate that this agent is highly active and well tolerated. Methods Eligible patients were accrued into an IRB approved treatment trial with pomalidomide and dexamethasone after signing informed consent. Pomalidomide (2 mg) and dexamethasone (40 mg) were scheduled to be taken orally, the former on a continuous schedule and the latter once weekly. All patients were instructed to take an aspirin daily. Patients were eligible if they had previously treated, biopsy proven, symptomatic AL. Patients were required to have measurable hematologic disease, defined as either a serum M-protein greater than 1 g/dL, a urinary M-protein greater than 200 mg/24-hours, or a serum immunoglobulin free light chain greater than 10 mg/dL. Other eligibility criteria included an ECOG PS>=2, adequate hematologic reserve (ANC>=1000/uL, platelets>=75/uL) and adequate renal function (creatinine <=2.5 mg/dL). They also were required to comply with contraceptive requirements. Patients were excluded if they had uncontrolled infection, another active malignancy, NYHA classification III or IV, a serum troponin T >0.1 ng/mL, >=grade 3 peripheral neuropathy, untreated active thrombosis, or other chemotherapy within 2 weeks of study enrollment. Thirty-four patients are to be enrolled to allow for 2 possible cancels and to provide 90% power to detect a true hematologic response rate of at least 20%. Between 11/24/08-7/28/09, 20 patients have been enrolled. Baseline characteristics and adverse events are available for 17 of the 20 enrolled patients. Results Median age was 63 years (range 52 78), with 60% male. The median time from diagnosis to study entry was 45 months (range 4.5-103). Eighty-two percent had cardiac involvement; 41% renal involvement; 18% peripheral nerve involvement; and 12% autonomic nerve involvement. The cardiac biomarker staging breakdown was: I, 13%; II, 56%; and III, 31%. Patients were heavily treated, with 100% having received prior alkylator (including prior transplant in 9), 44% prior lenalidomide, 31% prior thalidomide, and 37% prior bortezomib. Thirty-three percent of patients had non-hematological adverse events (AEs) >=grade 3 (severe) that were deemed to be at least possibly related to therapy. Thirty-three percent had >=grade 3 hematologic AEs. Neutropenia was most the most common severe hematologic AE; severe thrombocytopenia was observed in only 1 patient, and there was no severe anemia. The most common severe non-hematologic AE was fatigue, which was observed in 3 patients. The only other severe AEs, each of which was observed in one subject each, were pneumonia, weakness, dyspnea, and ascites. As of 8/14/09, 17 patients remain on active therapy. Median time on study is only 3.7 months (range 0.2-8.1). Three patients have discontinued therapy: two progressions; and one death 5 days into treatment, presumably due to cardiac amyloidosis. At the time of this writing response rates could not be calculated given the short follow-up, but hematologic responses have been observed, and details on efficacy will be presented at the meeting. Conclusions Pomalidomide is well tolerated in previously treated AL patients. More information about its activity will be provided at the meeting. Disclosures: Dispenzieri: Celgene: Research Funding. Gertz:Celgene: Honoraria. Kumar:Celgene: Research Funding. Rajkumar:Celgene: Research Funding. Witzig:Novartis: Research Funding. Greipp:Celgene: Research Funding. Fonseca:Celgene: Consultancy. Bergsagel:Celgene: Consultancy. Mikhael:Celgene: Research Funding. Roy:Celgene: Research Funding. Lacy:Celgene: Research Funding.

Abstract Abstract 3853 Poster Board III-789 Background Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by progressive multiorgan deposition of amyloid fibrils derived from immunoglobulin light chains. Treatment strategies for AL have typically targeted the clonal plasma cell and have paralleled that for myeloma, with recent clinical trials evaluating the role of novel agents such as immune modulatory drugs (IMiDs). Lenalidomide has activity in patients with AL, and given the synergy seen with alkylating agents, we designed a phase 2 clinical trial of cyclophosphamide added to lenalidomide and dexamethasone. Methods Patients (Pts) with newly diagnosed or previously treated AL, with adequate hematological and organ function, were enrolled between December 2007 and November 2008. Treatment consisted of 28-day cycles with Lenalidomide at 15 mg daily (days 1-21), oral cyclophosphamide 300 mg (days 1, 8, 15) and dexamethasone 40 mg weekly. All patients received aspirin for thromboprophylaxis. Hematological and organ responses were assessed using conventional response criteria. Results Thirty-five pts, 11 (31%) previously treated, with a median age of 64 yrs (range 44-82) were enrolled. Median time from diagnosis to trial enrollment was 1.6 mos (range; 0.1- 129) and 23 (66%) were alive at the time of analysis with a median follow up of 8.7 mos (range; 1.5-17.6). Three or more organs were involved in 10 (28%) pts with cardiac and renal involvement present in 22 (63%) and 27 (77%) respectively. Fifteen pts (44%) had advanced stage III disease by the troponin/ NT-ProBNP staging system. Seven (20%) pts had previous stem cell transplant, one pt had thalidomide and others had melphalan, dexamethasone or a combination of the two. The median duration on study was 6.5 months and the median number of cycles administered was 6, with 27 (77%) patients completing at least 3 cycles of therapy. Thirteen patients still remain on study, with the most common reason for study discontinuation being toxicity (10 pts, 45%). There were 15 (43%) and 24 (69%) episodes of Grade 3 or 4 hematologic and non-hematologic adverse events respectively. The most common non-hematologic toxicities seen were fatigue, edema, constipation and rash. Six patients died while on study due to sepsis (1), multiorgan failure (1), arrhythmia (1), or heart failure (3). The overall hematologic response rate was 60% (21 pts; CR (2), VGPR (10) and PR (9)); 79% for stage I and II pts and 40% for stage III patients. Among those patients receiving at least four cycles, the response rate was 20/23 (87%); 2CR, 10 VGPR and 8 PR. At least one organ response was documented in 8 (24%) patients. The median overall survival (OS) for all enrolled patients is 16.1 mos (95% CI; 10.8-NR). The median OS was not reached for stage I and stage II patients, and was 7 mos (95% CI; 4.6 - 16.1) for stage III pts. The median time to hematologic progression was 16.1 mos and to hematologic or organ progression was 6.7 mos (95% CI; 6.3, 16.1). The median OS among those with a hematologic response was 16.1 mos, and not reached among the group with a VGPR or better. Among the 31 patients with measurable FLC, those (n=24) with a ≥50% decrease in the difference between light chains had superior OS compared to the rest (16.1 mos vs. 4.3 mos). The six patients who died on study all had cardiac involvement and significantly higher NT-ProBNP/ BNP compared to the rest. Conclusion The combination of cyclophosphamide, lenalidomide and dexamethasone has significant activity in patients with light chain amyloidosis. Toxicity is manageable with dose reductions, but patients with advanced cardiac involvement are at a higher risk for toxicity and early discontinuation of therapy. Future trials with this combination should compare this regimen with other treatment approaches in selected patients, as well as pursue a dose-adapted strategy in those with advanced cardiac involvement. Disclosures: Kumar: CELGENE: Research Funding; MILLENNIUM: Research Funding; BAYER: Research Funding; GENZYME: Research Funding; NOVARTIS: Research Funding. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene: Research Funding.

Abstract Abstract 429 Background: Patients with MM who have progressed after multiple novel agents have limited treatment options. Pomalidomide (CC4047) is the newest immunomodulatory (IMiD) agent that has demonstrated response rates of 63% in a Phase 2 trial of Pom/dex in patients with relapsed MM (in press, JCO). To better define the response rate in this group, we treated an additional cohort of patients who were truly resistant/refractory to lenalidomide. Methods: To be eligible, patients must:be refractory to lenalidomide therapy defined as relapsing on or within 60 days of stopping lenalidomide. Pomalidomide was given orally 2 mg daily on days 1–28 of a 28-day cycle. Dexamethasone was given orally at a dose of 40 mg daily on days 1, 8, 15 and 22 of each cycle. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily as prophylaxis against DVT. Pom/dex regimen would be declared promising if we observed at least 4 confirmed responses out of 34 patients based on a single stage Fleming design. Results: 34 patients (23 male and 11 female) resistant/refractory to lenalidomide were enrolled. The median age was 62 years (range, 39-77). The median time from diagnosis to enrollment was 62 months (range 8-179). 12 patients had high risk molecular markers including loss of 17p (6 pts), t(4;14) (1 pt) and del 13 by cytogenetics (5 pts). 70% had ≥3 prior regimens including 38% with ≥5 prior regimens; 56% had prior thalidomide, 59% had prior bortezomib, and 68% had prior SCT. Toxicity (at least possibly related to treatment) was mild and consisted primarily of myelosuppression: grade 3/4 neutropenia (21%); grade 3 thrombocytopenia (9%); and grade 3 anemia (12%). Grade 3/4 non-hematologic toxicities occurred in 24%: pneumonia (3%), non-infectious pneumonitis (3%), hyperglycemia (3%), edema(3%), fatigue(9%) skin rash(3%). Neuropathy occurred in 18% (12% grade 1; 6% grade 2). No thromboembolic events have occurred so far. Nine (26%) patients were confirmed responders (all PR), surpassing the threshold for a positive trial, and 18 (53%) had SD. With a median follow-up of 4 months (range:0-8), 65% remain progression free; 88% remain alive; and 12% have died, all due to progressive MM. Conclusions: Pom/dex is active and well tolerated in this heavily pre-treated population of lenalidomide-refractory MM patients. The majority of patients have not progressed and objective responses are seen in 26%. This study confirms that pomalidomide has non-cross resistance with lenalidomide and offers benefit for patients who have relapsed after other novel therapies. Disclosures: Lacy: Celgene: Research Funding. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kumar:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bergsagel:Genentech, Inc.: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Merck: Research Funding. Stewart:Takeda-Millenium, Celgene, Novartis, Amgen: Consultancy; Takeda, Millenium: Research Funding; Genzyme, Celgene, Millenium, Proteolix: Honoraria.

Abstract Background: Thalidomide and its analogue lenalidomide have high response rates among patients with newly diagnosed as well as previously treated myeloma. Pomalidomide (CC4047) is the newest immunomodulatory (IMiD) agent that has shown single-agent activity in phase I studies. We report on the first Phase 2 trial of pomalidomide combined with low dose dexamethasone (Pom/dex) in patients with relapsed or refractory multiple myeloma. Methods: 37 patients (21 male and 16 female) were enrolled. Pomalidomide was given orally 2 mg daily on days 1–28 of a 28-day cycle. Dexamethasone was given orally at a dose of 40 mg daily on days 1, 8, 15 and 22 of each cycle. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily as prophylaxis against DVT. Results: The median age was 66 years (range, 40 – 88). All patients were evaluable for response and toxicity, and all analysis were done on intent to treat basis. All patients had received prior therapy; 38% had 3 prior regimens; 35% had 2 prior regimens and 27% had one prior regimen. 76% had previous autologous stem cell transplant (ASCT) and 24% had 2 prior ASCT. 62% had previous IMiD therapy. Toxicity was mild and consisted primarily of myelosuppression. Grade 3 neutropenia occurred in 31%; grade 3 thrombocytopenia 3%; grade 3 anemia 3 %. Other grade 3/4 toxicities seen in less than 5% pts included: diarrhea, atrial fibrillation, pneumonia, dehydration and renal insufficiency. 16 % had grade 1/2 neuropathy. No grade 3 neuropathy was seen and there have been no thromboembolic events. Thirty (81%) patients are continuing study treatment. Seven patients have discontinued treatment due to: disease progression (5), died on study (1) and the medical doctor’s discretion (1). Twenty three of 37 patients (62%) achieved an objective response to therapy; including 9 (24%) with VGPR; 14 patients (38%) with PR; 6 (16%) with stable disease. Objective responses were seen in 4 of 13 patients (29%) who were refractory to lenalidomide. Conclusions: Pomalidomide plus dexamethasone (Pom/dex) is highly active and well tolerated for treatment of relapsed/refractory multiple myeloma with an objective responserate of 62%, including a 29% response rate among patients who are lenalidomiderefractory.

Abstract Background: Relapse after ATRA-based induction therapy is relatively uncommon in patients with acute promyelocytic leukemia (APL). Long term follow up studies have estimated a 15-25% relapse rate. Autologous and allogeneic hematopoietic stem cell transplantation (HCT) has been used as an effective salvage strategy. We present a single institution study of the outcomes of patients with relapsed APL that underwent HCT. Methods: After due IRB approval, the Mayo Clinic Transplant Database was retrospectively reviewed to identify all patients across three Mayo Clinic sites with relapsed APL that underwent HCT from 1995-2013. Data was abstracted at diagnosis and at relapse. The aims of this study were to report the descriptive characteristics of patients, with a focus on HCT outcomes. Results: Baseline Patient Characteristics A total of 15 patients (9 (60%) males) with relapsed APL that underwent HCT were identified. Median age was 36 years (range: 19-63) and median follow up from diagnosis was 8.8 years (range: 1.7-17). 2 (13%) deaths (1 from relapse) were recorded. 14 (93%) received ATRA and anthracycline-based induction therapy and 1 received anthracycline-based induction without ATRA. All relapsed patients achieved a complete remission (CR) after induction. Median time to relapse was 1.6 years (range: 0.6-3.9). 10 (67%) patients had a medullary relapse (hematologic-7(70%), cytogenetic -2 (20%) and molecular-1(10%)), 3 (20%) had additional extramedullary (EM) disease (CNS-2, myeloid sarcoma-1), while 2 (13%) presented with EM disease only (CNS-2). Salvage regimens included ATRA in 5 (33%) patients and arsenic trioxide (ATO) in 8 (53%) patients. 12 (80%) patients were transplanted in CR2 and 1 in CR3 (7%), while 2 (13%) had persistent disease (PD) at time of HCT. Allogeneic HCT 4 (27%) patients with a median age of 37 years (range: 33-49) underwent allogeneic HCT. 2 (50%) patients received myeloablative (MA) conditioning and 2 received reduced-intensity conditioning (RIC). 2 patients who underwent MA HCT had PD at time of transplant, while 1 patient in CR3 received a RIC. 2 (50%) patients developed acute GVHD while 2 (50%) had extensive stage chronic GVHD. At a median follow up of 2.6 years (range: 0.3-10.9), 3 (75%) patients remain alive and disease-free. 1 patient died of infectious complications within 100 days of transplant. Autologous Transplantation 11 (73%) patients with a median age of 40 years (range: 23-68) underwent autologous HCT with MA conditioning. 7 (64%) patients were in molecular remission at time of HCT, 3 (27%) patients transplanted before 2004 were in cytogenetic remission and information about type of remission was unavailable in 1 patient. At a median follow up of 6.8 years (range: 0.5-16) since HCT, 1 (9%) patient had a documented relapse at 175 days after HCT and died of disease-related complications. 10 (91%) are alive and in remission. Conclusions: Our single-institution study reaffirms the efficacy of HCT for APL patients with medullary and EM relapse. Autologous HCT has excellent long-term results in selected patients in CR2. Allogeneic HCT was mainly reserved for patients with high risk disease (CR3) and persistent disease at time of HCT. Table 1: Baseline Patient Characteristics N (%) Number of patients 15 Follow up (years) (median, range) 8.8 (1.7-17) Age at diagnosis (years) (median, range) 36 (19-53) Gender Male 9 (60%) Female 6 (40%) Sanz risk score High 4 (29%) Intermediate 8 (57%) Low 2 (14%) Induction Regimen ATRA + anthracycline 14 (93%) Anthracycline-based 1 (7%) Response to induction therapy CR 15 (100%) Time from diagnosis to relapse (years) (median, range) 1.6 (0.6 - 3.9) Type of relapse Hematologic 7 (47%) Cytogenetic 2 (13%) Molecular 1 (7%) Hematologic and EM 3 (20%) CNS only 2 (13%) Salvage regimen ATRA-based 5 (33%) ATO-based 8 (53%) Chemotherapy only 2 (13%) Table 2: Outcomes at HCT N (%) Age at HCT (years) (median, range) 38 (23-68) Disease status at HCT CR2 12 (80%) CR3 1 (7%) PD 2 (13%) Type of HCT Allogeneic 4 (27%) Autologous 11 (73%) Conditioning regimen Myeloablative 13 (87%) Non-myeloablative 2 (13%) Follow up since HCT (years) (median, range) 4.5 (0.3 - 16.3) Disease status at last follow up CR 13 (86%) Relapsed disease 1 (7%) Unable to assess 1 (7%) Alive at last follow up 13 (87%) Disclosures No relevant conflicts of interest to declare.

Abstract Introduction Although allogeneic hematopoietic cell transplantation (HCT) is an expensive modality of treatment for hematological disorders, very little is known about the financial burden for the patients themselves. We analyzed factors associated with financial burden and its impact on health behaviors of allogeneic HCT recipients. Patients and Methods A questionnaire was mailed to adult patients who were alive after allogeneic HCT performed between 1/06 to 6/12 at Mayo Clinic to collect information regarding financial concerns, household income, employment status, insurance, out-of-pocket expenses and health and functional status. A multivariable logistic regression analysis was performed to determine socio-demographic and clinical factors associated with financial hardship. Results Of 482 patients, 268 responded (response rate 56%). Respondents were more likely to be older and Non-Hispanic Whites. No significant differences were seen in disease or transplant characteristics between the two groups except that respondents were more likely to have received reduced intensity conditioning. Median follow-up after HCT was 2.3 years (range 0.7-6.7 years). All the patients for whom the insurance information was available (missing n=13) were insured. Median physical and mental component score, as derived from the SF-12, were 36.8 [Interquartile range (IQR) 29.3-49.0] and 53.1 (IQR 42.1-57.1) respectively, where the general population score is 50, and lower scores indicate worse functioning. The proportion of patients that reported being on medical disability increased from 8% prior to HCT to 29% after HCT. 73% of the respondents reported that being sick had hurt them financially. 54% experienced adverse financial consequences such as decrease in household income by &gt;50% due to the HCT, need to sell/mortgage home, withdraw money from retirement accounts or having to pay more for medical care than they could afford. 3% declared bankruptcy. 12% had out-of pocket costs for the past 3 months that were&gt; $5000. Median monthly medication copayments were $100 (range $ 0-3000). 36% patients felt that their insurance coverage was poor which was strongly correlated with adverse financial consequences (p=0.0013). Other risk factors for financial burden were poor physical functioning reflected by the physical component score &lt;40 (OR 3.2; p=0.005), lower household income (OR 3.08; p=0.006) and lack of commercial/private insurance (OR 4.2; p&lt;0.001) while adjusting for patient and transplant related characteristics. Time from transplant was a significant predictor (OR 1.2; p=0.03) in the univariate analysis, but lost its significance in the multivariate analysis. 18 to 27% patients reported deleterious health behaviors due to financial constraints such as not taking prescribed medications, not using a recommended medical service or not making physician appointments. Conclusions A significant proportion of allogeneic HCT survivors experience adverse financial consequences with a few reporting severe outcomes like bankruptcy, despite having health insurance coverage. Future research should investigate potential interventions such as early financial counseling and connecting with sources of financial support to help at-risk patients and prevent long-term adverse financial outcomes after this life-saving procedure. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 863 Background: Patients with MM who have progressed after multiple novel agents have limited treatment options. Pomalidomide (CC4047) is the newest immunomodulatory (IMiD) agent. Pom/dex using a dose of 2 mg/day has demonstrated response rates (≥PR) of 63% in relapsed MM (Lacy, JCO 2009, 27:5008-5014) and 32% in a lenalidomide-refractory cohort (Lacy, Leukemia, in press). The maximum tolerated dose has been determined to be 4 mg/day for 21 of 28 days (Richardson, ASH, 2009), We opened two sequential phase II trials using the Pom/dex regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Methods: Patients refractory to both lenalidomide and bortezomib therapy; defined as relapsing on or within 60 days of stopping each regimen, were enrolled. Pomalidomide was given orally 2 mg daily (Cohort A) or 4mg daily (Cohort B) on days 1–28 of a 28-day cycle with oral dexamethasone given 40 mg daily on days 1, 8, 15 and 22. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis. Results: 35 patients with relapsed and resistant/refractory to both lenalidomide and bortezomib were enrolled in each cohort. The median age was 62 years (range, 39–77) in Cohort A and 61 (range, 45–77) years in Cohort B. The median time from diagnosis to enrollment was 57 months for Cohort A (range 12–249) and 72 months(range, 13–183) for Cohort B. 15 patients had high risk molecular markers in Cohort A and 16 in Cohort B. The median number of prior regimens was 6 in both groups. The median (range) duration on treatment was 5(1-13) and 2(0-6) cycles in cohorts A and B respectively. Toxicity at least possibly attributed to drug consisted primarily of myelosuppression: grade 3/4 neutropenia (37% Cohort A vs. 55% Cohort B); grade 3/4 thrombocytopenia (11% Cohort A vs. 13% Cohort B); and grade 3/4 anemia (9% Cohort A vs. 16% Cohort B). Grade 3/4 non-hematologic toxicities occurred in 23% Cohort A vs. 13% Cohort B. Grade 1 or 2 fatigue was the most common non-hematologic toxicity seen in 43% Cohort A vs. 52% Cohort B. Grade 1 or 2 neuropathy occurred in 17% Cohort A vs. 16% Cohort B. Other non-hematologic toxicities occurring in <5% included pneumonitis, hyperglycemia, renal failure, thrombosis. One patient in cohort B had grade 4 hepatitis. Confirmed responses in Cohort A consisted of VGPR 14%, PR 11%, and MR 24% (ORR 49%, 95% CI: 31–66), and responses in Cohort B consisted of VGPR 9%, PR 20%, and MR 12% (ORR 40%, 95% CI: 23–58). The median follow-up on alive patients was 7.5 months, and 3 months in Cohorts A and B, respectively. The median PFS in cohorts A and B are respectively 6.4 months (95% CI: 4.7-NR) and 3.3 months (95% CI: 2.3-NR). Conclusions: Pom/dex is remarkably active and well tolerated in this heavily pre-treated population of dual bortezomib/lenalidomide-refractory MM patients. The majority of patients have not progressed and objective responses (MR or better) are seen in 40–49%. This study confirms therapeutic benefit for Pom/dex in patients relapsing after other novel therapies. These studies do not show an advantage for the 4 mg/day on days 1–28 of each 28 day cycle did not show an advantage over the 2 mg/day on days 1–28 of each 28 day cycle. Disclosures: Lacy: Celgene: Research Funding. Gertz:Celgene: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Fonseca:Genzyme: Consultancy; Medtronic: Consultancy; BMS: Consultancy; AMGEN: Consultancy; Otsuka: Consultancy; Celegene: Consultancy, Research Funding; Intellikine: Consultancy; Cylene: Research Funding; Onyx: Research Funding; FISH probes prognostication in myeloma: Patents & Royalties. Bergsagel:Celgene: Consultancy; Centocor: Consultancy; Genentech: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Stewart:Celgene: Honoraria.

Abstract Abstract 3963 Background: Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with relapsed multiple myeloma (MM). Between November 2007 and November 2010, we opened 5 sequential phase 2 trials using the pomalidomide at differing doses with weekly dexamethasone (Pom/dex) regimen to study the efficacy of this regimen. Methods: The five cohorts consisted of: Cohort 1 (N=60): relapsed MM with 1–3 prior regimens, 2 mg dose; Cohort 2 (N=34): lenalidomide refractory, 2 mg dose; Cohort 3 (N=35): bortezomib/lenalidomide refractory, 2 mg dose; Cohort 4 (N=35): bortezomib/lenalidomide refractory, 4 mg dose; and Cohort 5 (N=60) lenalidomide refractory, 1–3 prior regimens, 4 mg dose. Pomalidomide was given orally 2 mg daily or 4mg daily on days 1–28 of a 28-day cycle with oral dexamethasone given 40 mg daily on days 1, 8, 15 and 22. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis or full dose anticoagulation. Results: A total of 225 patients were enrolled across all 5 cohorts. One patient was ineligible and excluded from analysis. The median age was 63 years (32.0–88.0). The median time since diagnosis was 53 months. Forty percent had high-risk molecular markers. Eighty-nine percent had received previous IMIDs including thalidomide (53%) and lenalidomide (81%). Sixty-two percent had previous bortezomib and 73% had prior transplant. The median follow-up is 12.6 months, but varies from 9.4 months for the most recent cohort to 30 months for the first cohort. Sixty-nine percent are alive and 30% remain progression free. Toxicities ≥ grade 3 are shown in table 1 and patient outcomes are shown in Table 2. Conclusions: Pom/dex is remarkably active and well tolerated even in heavily pretreated patients. Responses are durable. Response rates and toxicity are similar between the 2 mg and 4 mg doses. Disclosures: Lacy: Celgene: Research Funding. Fonseca:Consulting:Genzyme, Medtronic, BMS, Amgen, Otsuka, Celgene, Intellikine, Lilly Research Support: Cylene, Onyz, Celgene: Consultancy, Research Funding.

Abstract Abstract 987 Background: IMiD® compounds are effective in immunoglobulin light-chain amyloidosis (AL), a systemic plasma cell disorder related to multiple myeloma (MM). Pomalidomide is a new IMiD® compound. Methods: Persons with symptomatic, biopsy-proved, previously-treated AL were eligible for treatment with pomalidomide if they had measurable hematologic disease, ECOG PS≥2, adequate hematologic reserve and creatinine ≤2.5 mg/dL. Pomalidomide, 2 mg/d, and dexamethasone, 40 mg/w, were given orally along with low-dose aspirin. Dose-escalation to 4 mg/d was allowed for non-responders. Exclusion-criteria were uncontrolled infection, cancer, NYHA classification >II, serum troponin-T >0.1 ng/mL, ≥grade-3 neuropathy, thrombosis or other AL therapy within 2 weeks of enrollment. 31 subjects enrolled, but only 29 are evaluble for toxicity and response due to recent enrollment. Results: Median age was 66 y (range, 52 82 y); 19 were male. Median time from diagnosis to study-entry was 36 mo (range, 0.9–104.1 mo). 24 had cardiac involvement, 10, renal involvement and 8, nerve involvement. Cardiac biomarker staging was: I, N=3, II, 21, and III, N=7. Subjects were extensively pretreated: 28 received an alkylator (including an autotransplant in 13), 15, prior lenalidomide or thalidomide and 12, prior bortezomib. 193 cycles of pomalidomide were given to 29 subjects. 11 subjects had protocol-specified dose-increases (no response) and 16, dose-reductions (AEs). 20 subjects had dexamethasone dose-reductions. ≥Grade-3 AE's ≥possibly attributed to therapy occurred in 21 subjects. 7 of these subjects had only hematologic AE's. Neutropenia was the most common severe AE (N=10); severe thrombocytopenia occurred in 2 subjects. Other grade-3/-4 AEs included infection/fever (N=3); fatigue (N=4), and pleural effusion, ascites/edema, and edema each in one patient. 1 subject each had dyspnea, increased creatinine, thrombosis, muscle weakness, atrial tachycardia, and diarrhea. There were 2 episodes of syncope attributed to AL rather than therapy. A subject died 5 d after beginning therapy presumably from cardiac AL. As of 7/27/010, median time on-study is 8.4 mo (range, 0.2–16.2 mo). 18 subjects discontinued therapy for: progression/death (N=9); consent withdrawal (N=4), AE (N=3) and physician choice (N=2). Overall hematologic response rate (N=29) is 38% (95% CI, 20–58%) There were 8 PRs and 3 VGPRs including 4 PRs and 2 VGPRs among 14 subjects failing prior lenalidomide and/or thalidomide. 3 subjects had confirmed organ responses (2 heart and 1 kidney) and 4 unconfirmed organ responses. 1 y survival and PFS are 77% (95% CI, 60–98) and 56% (95% CI, 36–85). Conclusion: These data suggest that pomalidomide could provide a safe and effective therapy in previously-treated persons with AL including those failing lenalidomide and/or thalidomide. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Off Label Use: Non-FDA approved indication. Gertz:Celgene: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Fonseca:Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy, Research Funding; Genzyme: Consultancy; Onyx: Research Funding; Otsuka: Consultancy; Medtronic: Consultancy. Bergsagel:Celgene: Consultancy; Centocor: Consultancy; Genentech: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Stewart:Millennium: Consultancy; Celgene: Honoraria. Lacy:Celgene: Research Funding.

Abstract Background BT062 (Biotest AG Dreieich, Germany) is an antibody-drug conjugate, comprising the anti-CD138 chimerized MAb (nBT062) and the maytansinoid DM4 as cytotoxic agent. Once bound to CD138 on a target cell, the conjugate is internalized and releases DM4, leading to target cell death. CD138 (Syndecan-1) is highly overexpressed on various solid tumors and in hematological malignancies, and represents one of the most specific target antigens for identification of multiple myeloma (MM) cells. Data from two studies investigating BT062 as single agent demonstrated an acceptable tolerability profile and evidence of clinical activity in patients with heavily pretreated relapsed and/or refractory MM (1, 2). Preclinical studies showed enhanced anti-MM activity when BT062 was combined with lenalidomide and dexamethasone (Len/Dex). Based on these data, a Phase I/IIa study in MM was initiated to evaluate the safety and efficacy of BT062 in combination with Len/Dex. Objectives To determine the dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the recommended phase II dose (RPTD), pharmacokinetics (PK), and anti-MM activity of increasing doses of BT062 (days 1, 8, and 15, every 4 weeks) in combination with Len (25 mg, daily on days 1-21) and low dose Dex (40 mg on days 1, 8, 15, and 22) in patients with relapsed and/or refractory MM. Methods This is a prospective, open label, dose-escalation, multicenter Phase I/IIa study. The Phase I part includes dose escalation, and the Phase IIa the expansion of the MTD or RPTD cohort. Patients aged ≥18 years with relapsed and/or refractory MM who have failed at least one prior therapy were eligible to participate. Prior treatment with Len and/or Dex was allowed. Patients with clinical response (or no evidence of progressive disease) and without unacceptable toxicities were eligible for additional treatment cycles. Patients were enrolled in cohorts of at least 3 at each dose level; DLT in the first cycle triggered cohort expansion. Toxicities were assessed by CTCAE v4 and clinical response was assessed according to International Myeloma Working Group criteria. Results As of July 2013, a total of 15 patients have received BT062 at dose levels of 80 mg/m2 (N=3), 100 mg/m2 (N=6) or 120 mg/m2 (N=6). Two patients at the highest dose level discontinued study due to toxicity (DLT), another patient withdrew consent. The other 12 patients remain on treatment; median duration 144 days (range 8–385). The median number of prior therapies was 4 (range 1–11), 87% of patients had prior Len exposure, and 50% were Len/Dex refractory. The maximum administered dose (MAD) has been reached at 120 mg/m2, with mucosal inflammation (CTC grade 3) as DLT in one, and anemia (CTC grade 3) in a second of the 6 patients treated at this dose level. About 85% of reported Adverse Events (AE) were of CTC grade 1 or 2. The most common reported AEs were fatigue, hypokalemia, and diarrhea. Amongst the 9 patients currently evaluable for efficacy, responses were observed across all dose levels with a overall response rate (ORR) of 78%; including 1 patient with complete response (120 mg/m2), 1 patient with very good partial response (80 mg/m2), and 5 patients with partial response (80 and 100 mg/m2). Two other patients achieved disease stabilization, resulting in a clinical benefit in 100% of the evaluated patients. Interestingly, partial response was observed in 3 patients refractory to prior treatment with Len/Dex. The MTD has been defined as 100 mg/m2 and is currently expanded to further evaluate the safety and efficacy of BT062 at the RPTD. Conclusion Preliminary data from this ongoing study indicate that BT062 is well tolerated in combination with Len/Dex at dose levels that induce responses in patients with relapsed and/or refractory multiple myeloma, including Len/Dex-refractory patients. Updated results on safety and efficacy will be presented. References 1. Jagannath et al, BT062, an Antibody-Drug Conjugate Directed Against CD138, Shows Clinical Activity in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma. Blood. 2011; 118: Abstract 305. 2. Heffner et al, BT062, an Antibody-Drug Conjugate Directed Against CD138, Given Weekly for 3 Weeks in Each 4 Week Cycle: Safety and Further Evidence of Clinical Activity. Blood. 2012; 120: Abstract 4042. Disclosures: Somlo: Celgene: Research Funding, Speakers Bureau; NIH: Research Funding; Millennium: Speakers Bureau. Heffner:Genentech: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding. Siegel:Millennium: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Zimmerman:Celgene: Honoraria; Millennium: Honoraria; Onyx: Honoraria. Jagannath:Millennium: Honoraria; Celgene: Honoraria. Munshi:Celgene: Consultancy; Novartis: Consultancy; Millennium: Consultancy. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy. Ruehle:Biotest AG: Employment. Chavan:Biotest Pharmaceuticals: Employment. Patel:Biotest Pharmaceuticals: Employment. Rothenburger:Biotest AG: Employment. Wartenberg-Demand:Biotest AG: Employment. Haeder:Biotest AG: Employment. Anderson:Gilead: Consultancy; Sanofi Aventis: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Acetylon: Equity Ownership; Oncopep: Equity Ownership.