ALBERT

Description: Introduction: Survival rates continue to improve after allogeneic HCT (Gooley et al, NEJM, 2013). Population-based studies also indicate overall improvement in survival of older (60-80 years old) AML patients (pts) (Bower, Blood Cancer Journal, 2016). Yet, only a small minority (6%-8%) of them receive HCT (Medeiros, Ann Hematol. 2015). Given these potentially incongruent findings and the changing face of survival in AML, we designed the first prospective multi-center longitudinal study dating from first presentation of adults with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We compared survival according to whether or not pts received HCT at later time points. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including activities of daily living (ADL); frailty; geriatric assessment including cognition; QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale, ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. We used time-dependent Cox regression analyses to identify baseline and time-dependent risk factors associated with mortality in the overall population. The factors identified as significantly associated with mortality (p

Description: Background: High-dose chemo(radio)therapy (HDC) followed by auto-BM/PSCT is considered an acceptable therapeutic option for patients (pts) with R/R-HL. Various adverse prognostic factors have been previously described in this setting, including resistance to salvage therapy, active disease at the time of transplant, decreased performance status, B symptoms, extranodal disease, and complete remission duration of less than 1 year. On the other hand, overweight state (defined as BMI 〉 or = 28) was associated with reduced overall and event-free survival among pts who received HDC followed by auto-BM/PSCT for non-Hodgkin’s lymphoma. The prognostic significance of excess body weight among pts with R/R-HL who undergo HDC followed by auto-BM/PSCT has not been reported. Objective: To evaluate the relationship between excess body weight and overall survival (OS) in pts with R/R-HL who receive HDC followed by auto-BM/PSCT. Methods: A retrospective, single institution study of consecutive pts with R/R-HL who received HDC followed by auto-BM/PSCT at the University of Oklahoma over the last 19 years (1985– 2004) was performed. BMI was calculated as [weight (kg)/height2 (m)]. Overweight state was defined as BMI 〉 or = 28. OS was defined as the time period in months from the day of transplant until death, or the last of day of follow-up. Survival curves were estimated according to the Kaplan-Meier method, and were compared between the two groups (control group [BMI 〈 28] and overweight group [BMI 〉 or = 28]) with the use of the log-rank test. Median survivals of the two groups were also compared by using Wilcoxon-Mann-Whitney test. A two-tailed P-value of 〈 0.05 was considered statistically significant. SAS® sofware (version 8.0; Carry, NC) was used for statistical analysis. Results: 66 pts (40 males, 26 females) were identified, who were 13–69 years old (median 29 years) at the time of transplant. 40 pts (61%) died during follow-up, 4 pts (6%) were lost to follow-up at 15, 27, 58 and 103 months after transplant, and 22 pts (33%) are alive at the time of this analysis (7/30/04), 2–187 months (median 68 months) after transplant. 65 pts were included in this analysis (BMI could not be calculated for one pt). OS for the control group (n1= 42, 26/42 died) was 30 months (95% CI: 20–69 months) and for the overweight group (n2=23, 14/23 died) was 42 months (95% C.I. 8.0- N/A months). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8109 and 0.7367, respectively). Conclusion: Excess body weight is not a prognostic factor in patients with R/R-HL who undergo HDC followed by auto-BM/PSCT. A prospective study to evaluate and confirm our findings is warranted.

Description: Background: multiple myeloma (MM) remains an incurable disease that accounts for approximately 10% of all hematologic cancers. Patients (pts) with MM treated with conventional chemotherapy have a median overall survival of 36–42 months. Various adverse prognostic factors have been described in MM, including elevated B2 microglobulin, hypoalbuminemia, cytogenetic abnormalities of chromosome 13 (13q14 del, monosomy 13), and elevated CRP among others. BCL-2 mediates anti-apoptotic pathways and its expression has been implicated with lack of response to certain chemotherapeutic agents and unfavorable prognosis in different human malignancies. Objective: to evaluate the prognostic significance of BCL-2 expression in patients with MM. Methods: adult pts who were diagnosed with MM at our institution since 1/1/90 were retrospectively analyzed. Expression of BCL-2 was determined by immunohistochemistry (IHC) staining of deparafinized bone marrow specimens. Median survival was calculated for BCL-2 (+) and BCL-2 (−) groups. Survival curves were estimated according to the Kaplan-Meier method, and were compared with the use of the log-rank test. Median survivals were also compared by using Wilcoxon-Mann-Whitney test. Two-tailed alpha level of 0.05 was considered statistically significant. SAS® software (Cary, NC) was used for statistical analysis. Results: sixty-six patients were initially identified. Forty-four pts were excluded because bone marrow samples were not available for IHC staining. Twenty-two pts (11 males, 11 females), with a median age at the time of diagnosis of 64 years (range: 46 to 83 years) were included for this analysis. Fourteen pts (64%) had positive BCL-2 bone marrow specimens, including 4 mild, 3 moderate, and 7 strong staining, while for 8 pts (36%), bone marrow specimens did not stain for BCL-2. Twelve pts (86%) from BCL-2 (+) group and 4 pts (50%) from BCL-2 (−) group died during the period of follow-up; 8 pts are still alive at the time of this analysis, 23 to 71 months (median: 39 months) after diagnosis. The median survival among BCL-2 (+) pts was 35 months (95% CI: 24 – 69 months) and among BCL-2 (−) pts was 47 months (95% CI: 13 months - N/A). Overall survival did not differ between the two groups (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.8256 and 0.7072, respectively). Conclusion: although our study did not show correlation between BCL-2 expression and overall survival, median survival among BCL-2 (−) pts with MM was 34% longer than BCL-2 (+) pts. The authors recognize the limitations associated with this analysis including the retrospective nature of the study, small sample size, and exclusion of a large number of patients. This study highlights the need for prospective evaluation of the prognostic significance of BCL-2 expression among pts with MM.

Description: Background: Chemoimmunotherapy regimens remain the preferred first-line treatment for most of patients with CLL/SLL. Recent studies have demonstrated the efficacy of maintenance regimens by improving progression-free survival (PFS). We studied safety and efficacy of a treatment protocol that included induction and maintenance components using vorinostat, a histone deacetylase inhibitor, in combination with FCR for induction and with rituximab for the maintenance. Methods: Previously untreated CLL/SLL patients with indication for treatment were eligible. Primary objective of the Phase I part was the maximum tolerated dose (MTD) of vorinostat that could be combined with FCR and PFS was the primary endpoint for phase II. In the induction phase, FCR (fludarabine 25 mg/m2 days 1-3, cyclophosphamide 250 mg/m2 days 1-3 and rituximab 375 mg/m2 on day 1 of cycle 1 and 500 mg/m2 on day 1 of subsequent cycles) was given every 28 days for 6 cycles. In addition to FCR, patients received vorinostat orally on days 1-5 and days 8-12 of each treatment cycle. In the dose finding phase, vorinostat was given at 3 dose levels: 200 mg, 300 mg and 400 mg PO daily. There was no dose limiting toxicity and 400 mg was chosen as the MTD for phase II. Patients who received at least 4 cycles of induction were eligible to receive maintenance beginning within 3 months of the last cycle of FCR. In the maintenance phase, given every 3 months for 8 cycles, rituximab was given at dose of 500 mg/m2 on day 1 and vorinostat was given at 400 mg PO daily on days 1-14 of each cycle. Results: 40 patients (CLL 32, SLL 8) were treated. Median age was 58 years (36-72). Median time from diagnosis to treatment was 27 months (0 -102). Rai stage at the time of treatment was I/II in 23 (60%) and III/IV in 17 (40%) patients. Cytogenetic (CG) abnormalities included del17p in 2 (5%), del11q in 2 (5%), trisomy 12 in 4 (10%), del13q in 3 (7.5%), normal CG in 14 (35%) and other abnormalities in 6 (15%) patients. Median number of induction cycles was 6 (1-6) and 33 patients (83%) patients finished at least 4 cycles of induction and were eligible for maintenance. Reasons for delivery of less than 4 induction cycles were patient preference (2), GI toxicity (1), thrombocytopenia (1), pulmonary emboli (1), progressive disease (1) and sepsis (1). Twenty-six patients (65%) received at least 1 cycle of maintenance treatment (median 8; range, 1-8) and 15 patients (40%) finished all 8 planned maintenance cycles. Eleven patients started maintenance treatment but did not receive all 8 maintenance courses due to neutropenia (3), patient preference (3), infections (1), insurance issues (1) or other reasons (3). Six patients (15%) were eligible for maintenance but did not receive it because of hematologic toxicities (3), infection (1) or patient preference (2). Overall response rate after induction was 91% with CR in 26 (74%), PR in 4 (11%), nPR in 2 (6%) and stable disease (SD) in 1 (3%). One patient (3%) had progressive disease during the induction and 1 (3%) was not evaluable. Twenty-one of 23 (88%) patients who achieved CR after induction, were tested for minimal residual disease (MRD) by flow cytometry and cytogenetics and 21 (91%) had negative MRD status. One of 2 CR patients who was MRD positive after induction converted to MRD negative after maintenance. After median follow-up of 42 months, 5-year estimate of overall survival was 90% (95% CI 75%-96%) and 5-year estimate of PFS was 72% (95% CI 51%-85%). None of the patients who achieved CR after induction (n=26; 74%) had disease progression after median 46 months of follow-up while 3 of 6 patients with PR or nPR had disease progression which occurred median of 40 months (29-51). Most common grade 3-4 toxicities were hematologic (36%), electrolyte abnormalities (9%), gastrointestinal (8%) and cardiovascular (6%). 4 patients (10%) died during the follow-up because of disease progression (1), sepsis (1), fungal infection (1) and suicide (1). Median time to death was 9.5 months (5 -20). Conclusion: Combination of vorinostat with FCR for induction and with rituximab for maintenance was feasible and effective with a high ORR and long OS and PFS with no relapses observed among patients who achieved CR after induction. Cytopenias and infections were main reasons for treatment discontinuation especially during the maintenance phase. Combination of novel agents with conventional induction and maintenance regimens is a promising strategy for treatment of CLL/SLL. Disclosures Shadman: Gilead: Honoraria, Research Funding; Emergent: Research Funding; Acerta: Research Funding; Pharmacyclics: Honoraria, Research Funding. Gopal:Paid Consultancy- Gilead, Janssen, Seattle Genetics, Spectrum, Research funding- Gilead, Janssen, Pfizer, BMS, Merck, Teva, Takeda, Spectrum, Seattle Genetics: Consultancy, Honoraria, Research Funding. Press:Roche / Genentech: Consultancy, Research Funding. Maloney:Juno Therapeutics: Research Funding; Genentech/Roche: Consultancy, Honoraria.

Description: Introduction: Acute myeloid leukemia (AML) is most frequently diagnosed in older patients (pts), whose median survival is less than 1 year. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. However, older pts often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. To this end, we designed a prospective, multi-center, longitudinal, observational study dating from first presentation of adult pts with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including instrumental activities of daily living (IADL) and activities of daily living (ADL); frailty including walk test; geriatric assessment (GA) including cognition; Karnofsky performance status (KPS); QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale (EQ-5D), ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. High-risk myelodysplastic syndromes (MDS) receiving AML-like therapy were included. We used competing risk Cox regression analyses, treating HCT as the event of interest and death without HCT as a competing risk, with staggered entry (left truncation) at time of consent. Associations between variables were assessed both at enrollment and over time. Results: The overall rate of HCT at 9 months after enrollment was 43% (Figure 1) and 92% of pts who received HCT did so by the 9 month mark. In multivariate analyses, death without HCT (Table 2) was associated with augmented HCT-CI scores ≥5 (HR:2.11, p

Description: Background The limitations of current CLL/SLL treatments include suboptimal response rates, variable remission durations, toxicities, and few cures. Vorinostat is a histone deacetylase inhibitor that regulates gene transcription and possibly CD20 expression, leading to its investigative use in the treatment of B-cell malignancies. For this reason, we studied the addition of vorinostat to fludarabine, cyclophosphamide and rituximab (FCR+V) followed by maintenance therapy with rituximab and vorinostat. Methods Patients over age 18 with previously untreated Rai stage I-IV CLL or SLL and ECOG 0-2 were eligible. They received 4-6 cycles of FCR+V followed by up to eight cycles of maintenance with rituximab and vorinostat. Each cycle of FCR used cyclophosphamide 250 mg/m2 IV on days 1-3 and fludarabine 25 mg/m2 IV days 1-3 of each cycle given every 28 days; with rituximab 375 mg/m2 IV once with cycle 1 followed by 500 mg/m2IV once per cycle for cycles 2-6. Rituximab 500 mg/m2 IV was given day 1 of each 3 month cycle of maintenance for up to 8 cycles. Vorinostat was given on days 1-5 and 8-12 of each treatment cycle and days 1-14 of each 3-month maintenance cycle. The Phase I vorinostat starting dose was 200 mg/day and escalated by 100 mg/day to a maximum pre-determined dose of 400 mg/day in a 3 x 3 design. Since no dose limiting toxicity was seen during Phase I, the previously designated maximum dose of 400 mg/day vorinostat was chosen for the Phase II portion of the trial. Results Ten patients were treated on the Phase I portion of the study, and 26 patients have been enrolled in the Phase II portion at the maximum vorinostat dose of 400 mg/day combined with FCR and rituximab maintenance. The median age of patients on study was 58 (range, 36-72); with 6 patients enrolled with Stage I, 15 with Stage II, 5 with Stage III and 10 with Stage IV disease. Nine patients (25%) had 〉30% CD38 expression, 13 patients (36%) had 〉20% ZAP70 expression, and 4 patients (11%) had 17p deletions detected by FISH of marrow samples. Median follow-up on study is 15 months (range, 0.9-38.6). Of the 36 patients enrolled, 22 patients are evaluable after completing 4-6 cycles of FCR+V, 1 patient progressed after cycle 2 (del17p), 9 patients are currently receiving FCR+V and 4 patients are unevaluable. Of these 4 patients, one withdrew voluntarily, one was taken off study due to non-compliance, one went off study after cycle 3 due to cytopenias, and one patient with multiple co-morbidities died of sepsis after cycle 5. Of the 22 patients who have completed 4-6 cycles of FCR+V, 16 (73%) obtained a complete response (CR), 5 (22.5%) obtained a partial response (PR), and 1 (4.5%) has stable disease. Of these 22 patients, 4 (18%) have completed 8 cycles of maintenance with rituximab and vorinostat, 5 (23%) were taken off study due to cytopenias, 1 (4.5%) went off study due to insurance issues, 1 (4.5%) went off study due to recurrent infections, 2 (9%) voluntarily withdrew from study, and 9 (41%) are still receiving maintenance therapy. The most common grade 3-4 non-hematologic toxicities during FCR+V were gastrointestinal symptoms in 10 patients and fatigue in 3 patients. However, there were no grade 3-4 non-hematologic toxicities that resulted in patient withdrawal from study during treatment with FCR+V. No grade 3-4 non-hematologic toxicities have been observed in patients who have completed or are undergoing maintenance with rituximab and vorinostat. Conclusion Treatment of CLL/SLL with fludarabine, cyclophosphamide, rituximab and 400mg/day vorinostat (FCR +V) followed by maintenance with rituximab and vorinostat appears feasible and tolerable, and may warrant further study. Disclosures: Gopal: Merck: Research Funding. Press:Roche/Genentech: Consultancy.

Description: Splenectomy has been a standard treatment for adult patients with idiopathic thrombocytopenic purpura (ITP) for more than 50 years. However, the durability of responses, the ability to predict who will respond, and the frequency of surgical complications with splenectomy all remain uncertain. To better interpret current knowledge we systematically identified and reviewed all 135 case series, 1966 to 2004, that described 15 or more consecutive patients who had splenectomy for ITP and that had data for 1 of these 3 outcomes. Complete response was defined as a normal platelet count following splenectomy and for the duration of follow-up with no additional treatment. Forty-seven case series reported complete response in 1731 (66%) of 2623 adult patients with follow-up for 1 to 153 months; complete response rates did not correlate with duration of follow-up (r = -0.103, P = .49). None of 12 preoperative characteristics that have been reported consistently predicted response to splenectomy. Mortality was 1.0% (48 of 4955 patients) with laparotomy and 0.2% (3 of 1301 patients) with laparoscopy. Complication rates were 12.9% (318 of 2465) with laparotomy and 9.6% (88 of 921 patients) with laparoscopic splenectomy. Although the risk of surgery is an important consideration, splenectomy provides a high frequency of durable responses for adult patients with ITP. (Blood. 2004; 104:2623-2634)

Description: Background: Management of R/R-HL has been disappointing with salvage chemotherapy alone. Although controversy remains over the best time to perform a transplant, auto-BM/PSCT is considered an acceptable salvage therapeutic option for patients (pts) with R/R-HL. Hypoalbuminemia is one of the seven adverse prognostic factors for newly diagnosed pts with HL who receive chemotherapy according to the international prognostic factors project on advanced HL. The prognostic significance of hypoalbuminemia in pts with R/R-HL undergoing salvage auto-BM/PSCT is less clearly defined at the present time. Objective: To evaluate the prognostic significance of hypoalbuminemia in pts with R/R-HL who undergo salvage auto-BM/PSCT. Methods: A retrospective, single-institution study of consecutive pts with R/R-HL who received auto-BM/PSCT at the University of Oklahoma over the last 19 years (1985– 2004) was performed. The serum albumin level during hospital admission for transplant that was closest to, but before, high-dose chemotherapy was recorded and used for this analysis. Hypoalbuminemia was defined as a serum albumin level 〈 3.5 g/dl. Overall survival (OS) was defined as the time period in months from the day of transplant until death, or the last day of follow-up. Survival curves were estimated according to the Kaplan-Meier method, and were compared between the two groups (control group [≥3.5 g/dl] and low albumin group [〈 3.5 g/dl]) with the use of the log-rank test. Median survivals of the two groups were also compared by using Wilcoxon-Mann-Whitney test. One-sided P-value of 〈 0.05 was considered statistically significant. SAS® sofware (version 8.0; Carry, NC) was used for statistical analysis. Results: 66 patients (40 males, 26 females) were identified, who were 13–69 years old (median 29 years) at the time of transplant. 40 pts (61%) died during follow-up, 4 pts (6%) were lost to follow-up at 15, 27, 58 and 103 months after transplant, and 22 pts (33%) are alive at the time of this analysis (7/30/04), 2–187 months (median 68 months) after transplant. Median survival for the control group (n1=27, 13/27 died) was 78 months (95% CI: 23 - N/A months) and for the low-albumin group (n2=39, 27/39 died) was 22 months (95% CI: 13– 44 months). The difference between overall survival curves (figure) and also the difference between median survivals approached, but did not reach statistical significance (p-values for log-rank and Wilcoxon-Mann-Whitney tests, 0.0632 and 0.0565, respectively). Conclusion: Our results suggest a trend for a worse outcome among pts who undergo salvage auto-BM/PSCT for R/R-HL with low serum albumin (

Description: Abstract 3650 Background: Traditional salvage strategies for relapsed lymphoma are less effective when disease recurs after modern front line therapies (e.g. R-CHOP, BEACOPP). Furthermore, typical multi-agent regimens require inpatient hospitalization and carry the risk of significant non-hematologic toxicity from drugs such as ifosfamide, high-dose cytarabine, and cisplatin. Bendamustine (Treanda ®, T) has both broad spectrum clinical activity in lymphoma and a moderate side effect profile, though limited data exist on the utility of this agent as part of a dose-intense rescue approach. We, thus, hypothesized that bendamustine could safely supplant ifosfamide within the RICE regimen yielding a feasible, effective, outpatient multi-agent salvage strategy (TREC) for patients with relapsed or refractory lymphoma. Methods: Eligibility included: relapsed/refractory lymphoma (untreated T-NHL or MCL was allowed during stage 1), age ≥18 years, performance status of 0–2, measurable disease, no active CNS involvement, ANC 3 1,500/μL, platelets 3 100,000/μL, adequate hepatic and renal function, no active arrhythmias, and no known HIV. The primary objective of the study was to define a maximally tolerated dose (MTD) of bendamustine associated with a dose limiting toxicity (DLT) rate of ≤25%. A DLT was defined as any related non-hematologic grade ≥4 adverse event (AE), or inability to complete one full cycle of therapy due to toxicity. Therapy was delivered in the outpatient setting and consisted of bendamustine ranging from 60 mg/m2 to 120 mg/m2 daily on days 1 and 2 in combination with carboplatin (AUC = 5 on day 1), etoposide (100 mg/m2 on days 1 to 3) and rituximab (375 mg/m2, for CD20+ disease only on either day 2 or 3) every 21 days for up to 2 cycles with G-CSF support. Single patient dose escalation occurred until a DLT was observed, followed by cohorts of 4 patients up to a maximum dose of 120mg/m2 × 2. Response was measured by standard criteria (Cheson 2007). AEs were graded using the CTCAE v4.0 Results: Twenty-four patients were treated, 4 in stage 1, and 20 in stage 2 with no DLTs observed. Baseline features included median age = 58 (range 18 – 72) years, median prior therapies = 1 (range 0 – 2), and refractory to last regimen = 16 (of 22 evaluable, 73%). All B-NHL patients had disease progression following prior rituximab. Histologies included Hodgkin lymphoma (HL, n = 8), diffuse large B-cell (DLBCL, n = 9), mantle cell (n = 2), T-NHL (n = 2), follicular (n = 2), and lymphoplasmacytic lymphoma (n = 1). Twenty-three patients received 2 cycles and one received 1 cycle due to disease progression. All cycles were given in the outpatient settings. Thirteen non-hematologic AEs ≥ grade 3 (SAEs) were observed in 9 patients. The most common related SAEs were dehydration (2), and febrile neutropenia (2). Responses were observed in 16 patients (67%) with 9 CR, and 7 PR. Response rates in HL and DLBCL were 88% (6CR, 1PR), and 56%. Mobilization of peripheral blood stem cells (PBSC) was successful in all 15 attempts immediately following the second cycle of T(R)EC (median yield: 5.58×106CD34/kg, range 3.96 – 11.68). At the last update with a median follow up of 8 (range 2 – 18) months, 19 (79%) patients are alive, and 13 (54%) are progression free, including 10 of 12 who subsequently underwenttransplant. Conclusions: This multicenter phase I trial confirms the ability to safely replace ifosfamide with 120mg/m2 × 2 of bendamustine, yielding the TREC regimen for patients with relapsed/refractory lymphoma. The outpatient administration, manageable toxicity profile, effective use for PBSC mobilization, and preliminary response data are encouraging. These data support future evaluation of TREC, including our ongoing expansion cohorts further investigating outcomes in patients with DLBCL and HL. Disclosures: Budde: Teva: Research Funding. Gopal:TEVA: Research Funding.

Description: Abstract 5038 Background: Combination regimens have been highly effective in multiple myeloma. Based on our results with the combination of bortezomib, cyclophosphamide, dexamethsone (Bensinger et al Br J Haematol 2010), we added liposomal doxorubicin to assess whether we could improve response as well as evaluate a weekly combination regimen at our academic center and network affiliated sites in the community. The trial is registered as NCT00849251. Methods: We initially evaluated the regimen in the relapsed setting for toxicity and found it to be well tolerated in 6 patients, then moved to newly diagnosed patients, with the intent that the regimen would serve as induction chemotherapy in preparation for autologous stem cell transplant for transplant-eligible patients. The dosing was bortezomib 1. 6 mg/m2 IV, cyclophosphamide 300 mg/m2 IV, and dexamethasone 40 mg po, days 1, 8, 15, and a single dose of liposomal doxorubicin 30 mg/m2 on day 8 per 28 day cycle. Patients received a maximum of 4 cycles of therapy and the primary endpoints were safety and response at the end of treatment. Results: A total of 31 out of the planned 45 patients (both newly diagnosed and relapsed) were enrolled, as the trial was ended early due to inability to obtain liposomal doxorubicin (Doxil®) for a period of 6 months. One of the relapsed patients was administratively withdrawn after the cycle 1 day 1 treatment. For the remaining 5 relapsed patients who received 2–4 cycles of treatment, the responses were 1 VGPR that was only immunofixation positive, 1 PR and 3 stable disease (SD). For the 24 patients with newly diagnosed MM who completed 1–4 cycles of treatment, there were 2 complete remissions (CRs), 5 VGPRs (2 of which were only immunofixation positive), 11 PRs, and 6 SD for an overall (CR+VGPR+PR) response rate of 75%. Five patients did not complete 4 cycles of therapy, one due to massive pulmonary embolism, one because of need for radiation for intractable back pain during cycle 2 despite marked serological response, and 3 due to stable disease with plateau in response. Of the 25 patients who received BCDD as initial therapy, there have been 3 deaths to date, one due to massive pulmonary embolism on day 13 of the first cycle of treatment, without known history of hypercoagulable risk, one at 7. 7 months of unknown cause, and one at 15. 3 months of progressive disease, resulting in an estimated overall survival of 86% at 2 years from start of therapy. Median follow-up among the 22 survivors is 16. 6 months (range, 8. 1 to 26. 8 months). One patient with a known central line associated deep venous thrombosis in the relapsed group did not exhibit progression of thrombosis off warfarin during therapy. After enrollment of the first 9 patients, an amendment was filed for subsequent patients to receive aspirin prophylaxis, or if at high risk by criteria suggested by Palumbo et al for prophylaxis for MM patients on imids, with low molecular weight heparin or warfarin. Other adverse events that were attributed to investigational regimen include grade 3 hand/foot syndrome (2), infection without neutropenia (1), urinary tract infection (1), and gastrointestinal hemorrhage due to Mallory-Weiss tear (1). Twenty-one patients who completed therapy went on to successful mobilization and collection of peripheral blood stem cells, and autologous or tandem autologous (2) or tandem autologous-minimal myeloablative allogeneic stem cell transplant (7). Two of the 21 patients have died (one at 2. 1 months after first autologous transplant from unknown cause, and one at 9. 8 months from progressive disease). Median follow-up after first autologous transplant among the 19 survivors is 13. 4 months (range, 1. 1 to 20. 4 months). Summary: The 4 drug BCDD regimen exhibited a 75% overall response rate after 4 cycles, with no progression during treatment, was able to be administered weekly in an outpatient setting of both academic and community hematologists and oncologists, and successfully prepared patients for autologous stem cell transplant. Disclosures: Becker: Millennium: Research Funding. Bensinger:Millennium: Research Funding.