ALBERT

Description: Abstract 4142 Introduction: High dose chemotherapy combined with autologous stem cell transplantation (ASCT) as opposed to conventional chemotherapy improved progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) and is currently the standard of care for newly diagnosed MM patients less than 65 years old. Over the last decade, novel agents such as lenalidomide or bortezomib have dramatically improved MM outcomes with similar response rates as ASCT and the role of upfront ASCT has become more controversial. Therefore the goal of this randomized clinical trial is to determine the role of upfront ASCT in newly diagnosed myeloma patients receiving novel agent lenalidomide and low-dose dexamethasone induction. Methods: Patients aged ≥18 years with newly confirmed, measurable MM in stage 2 and 3 (Salmon Durie) and meeting CRAB criteria were enrolled. Patients were randomized to transplant (Arm A) or to non-transplant (Arm B). Patients in Arm A received 4 cycles of lenalidomide (25mg days 1 – 21) plus low-dose dexamethasone (40mg days 1,8,15,22) followed by ASCT conditioned with 200 mg/m2 melphalan (LD+ASCT); Arm B patients received 8 cycles of lenalidomide plus low-dose dexamethasone (LD alone). Both arms received stem cell collection after 4 cycles of therapy if patients achieved at least a partial remission (PR). Patients with stable disease (SD) or progressive disease (PD) went off study. The primary objective was to compare best response. The secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS) and evaluation of secondary malignancies in both arms. Results: From February 2008 to May 2011, 44 patients with newly diagnosed MM were randomized. The patient characteristics were as follow: median age of the patients was 61.7 years (range 48∼75), 45.5% female and 55.5% male patients, ISS stage I 31%, II 51% and III 18%. 40 patients were eligible for evaluation and 20 patients were randomized to Arm A or Arm B, respectively. The data were analyzed according to latest IMWG response criteria (Blood. 2011 May 5;117(18):4691–5). In an intention to treat analysis, patients in Arm A (LD + ASCT), achieved a 100% Overall Response Rate (ORR) with 40% PR (n=8) and 60% Very Good Partial Response (VGPR) (n=12). In Arm B (LD only) the ORR was 75% (n=15), including 15% CR (n=3), 35% VGPR (n=7), 25% PR (n=5), 20% SD (n=4) and 5% PD (n=1). The ORR was significantly superior in the LD+ASCT group compared to LD alone (p=0.047). After a median follow-up of 25.3 months, 17 patients have PD (8 in LD+ASCT and 9 in LD alone), 6 have died (1 in LD+ASCT and 5 in LD alone). DOR, PFS and OS were not significantly different in both groups. OS showed a trend to be superior in patients treated with LD+ASCT (p=0.08). (Table 1). One patient in the LD+ASCT arm developed MDS 13 months after start of therapy. Conclusion: Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed MM patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR. There was no difference in terms of DOR or PFS with a trend of superior OS in the LD+ASCT group. The study requires careful interpretation based on the low patient number and relatively short follow up, but supports the continued role of upfront consolidative ASCT in newly diagnosed MM patients. The incidence of secondary malignancy was low with the development of 1 MDS. Updated data on response and overall survival will be available at the time of presentation. Disclosures: Roodman: Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Raptis:Millennium: Speakers Bureau; Celgene Corp: Speakers Bureau; Eisai: Speakers Bureau. Lentzsch:Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria.

Description: Background Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor with current therapeutic options. Preclinical studies suggest that "epigenetic priming" using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Interim response rates were reported at the ASH Annual Meeting in 2014. Here we present updated response rates, treatment-related mortality, and overall survival. Methods This is a phase 2, single arm study at the University of Pittsburgh Cancer Institute (NCT01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consisted of decitabine 20mg/m² intravenously (IV) x 5 days followed by cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceeded with maintenance decitabine after count recovery; patients otherwise proceeded with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle were taken off study. After a second induction cycle, patients who achieved a complete or partial remission proceeded with maintenance decitabine. Maintenance cycles consisted of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression or toxicity. Response rates were determined by the International Working Group Response Criteria in AML. Four-week and 8-week mortality rates were assessed. Results Forty-six subjects were enrolled as of August 2015, 36 of whom were evaluable for response at the time of analysis. Median age was 76 years (range 67-88 years). There were 21 females (45%) and 26 males (55%). The median ECOG performance status was 1. There were 21 patients with poor risk cytogenetics at diagnosis. Of 36 patients who were evaluable for response, 20 patients had a CR and 5 patients had a CRi (CR/CRi rate 69%). Six patients had a partial remission, and 5 patients had resistant disease. All evaluable patients except for 6 received 2 cycles of induction. There were no 4-week mortalities and 4 (8.6%) 8-week mortalities. Deaths were attributed to subdural hemorrhage, multifactorial respiratory failure, progressive AML, and neutropenic sepsis. At a median follow up of 13.5 months, the overall survival is 12.4 months (95% CI:9.7-12.5). Conclusion We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR/CRi rates with low treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the updated report of this phase 2 study, 69% of patients achieved a CR/CRi, and 4- and 8-week mortality were 0% and 8.6%, respectively. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Overall survival was 12.4 months, which also compares favorably to previous reports of survival in this patient population. Methylation analyses at baseline and after decitabine in patients who achieved CR compared to patients who did not respond are ongoing and will be reported. We have demonstrated that decitabine followed by cytarabine is safe and effective in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Description: Background: Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most older patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor after current therapeutic options in this patient population. Preclinical studies suggest that “epigenetic priming” using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this phase II study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Here we present response rates and treatment-related mortality for the first 23 evaluable subjects. Methods: A phase II, single arm study of decitabine and cytarabine is ongoing at the University of Pittsburgh Cancer Institute (NCT 01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consists of decitabine 20mg/m² intravenously (IV) x 5 days followed by standard dose cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceed with maintenance decitabine. Patients with persistent disease but no evidence of progression proceed with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle are taken off study. After a second induction cycle, patients with no evidence of disease, or persistent disease but no evidence of progression, proceed with maintenance decitabine. Maintenance cycles consist of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression. Response rates are evaluated by the International Working Group Response Criteria in AML. Treatment-related mortality is defined at mortality within 8 weeks of initiation of induction therapy. Results: Twenty-five subjects of a planned 37 subjects have been enrolled as of August 2014, 23 of whom were evaluable for response at the time of analysis. At the time of this preliminary analysis, the median age was 76 years (range 68-82 years). There are 11 females (44%) and 14 males (56%). The median ECOG performance status was 1 (range 0-2). There were 14 patients with poor risk cytogenetics at diagnosis. Of the 23 patients who are evaluable for response, there were 14 (61%) patients with a CR and 2 patients with a CRi (CR+CRi rate 70%). Two patients had a partial remission, 1 patient had a morphologic leukemia free state, and 4 patients had resistant disease. All patients except for 2 received 2 cycles of induction. Of the 14 patients who had poor risk cytogenetics at diagnosis, 10 (71%) had a CR, and 8 had normalization of their previous cytogenetic abnormalities. There have been no treatment-related mortalities to date. Conclusion: We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR+CRi rates with no treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the first report of this phase II study, 70% of patients achieved a CR or CRi, and there were no treatment related mortalities. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Final analysis of this clinical trial will include overall survival analysis, rate of grade III and IV adverse events, and epigenetic correlative studies. We have demonstrated that decitabine followed by cytarabine is a safe and effective regimen in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Description: Background: Acute myeloid leukemia (AML) carries a poor prognosis in older adults. Limited clinical trial data exist to support the use of conventional cytarabine-based regimens in this population, and practice standards have been extrapolated from studies in younger patients. Intensive chemotherapy in older adults is associated with high rates of treatment-related mortality and poor overall survival. In 2010, Kantarjian and colleagues developed a risk model for 8-week mortality using adverse prognostic risk factors, including age ≥80 years, complex karyotype (≥3 abnormalities), poor performance status (ECOG score ≥2), and serum creatinine 〉1.3 mg/dL. This study validates the Kantarjian model for progression-free survival (PFS) and overall survival (OS) in older patients with AML treated with intensive chemotherapy. Methods: Adults aged ≥70 years with AML (≥20% blasts in bone marrow or peripheral blood) who received intensive chemotherapy at UPMC Hillman Cancer Center between 2000 and 2011 were evaluated. Patients were stratified into low, intermediate, and high-risk groups according to the Kantarjian (2010) model and analyzed for PFS and OS using the Kaplan-Meier method. Differences in PFS and OS between risk groups were assessed with the log-rank test. ECOG performance status was estimated using historical data at the time of diagnosis. Additional variables, including AML type (primary vs. secondary), percent blasts at diagnosis, percent CD34-positive blasts, hemoglobin, leukocytes, platelets, LDH, AST, ALT, total bilirubin, albumin, and Charlson comorbidity index (CCI) were tested for added prognostic value when incorporated into the model, using Cox proportional-hazards regression for PFS and OS. Results: Clinical data were collected for 68 patients. Of these, 26 patients, all of whom were diagnosed prior to 2003, were excluded from the final analysis due to insufficient electronic health records. The remaining 42 patients were used for the validation study. Median age at diagnosis was 73 years (range: 70-87). Twenty-seven patients (64%) had primary AML, whereas 10 (24%) had AML evolving from another hematologic disorder and 5 (12%) developed AML after radiation or chemotherapy for another malignancy. Eleven (26%) patients had ≥3 karyotypic abnormalities and the remaining 31 (74%) had fewer than 3. Thirty-three (79%) patients had an ECOG performance status of 0 or 1, and the remaining 9 (21%) did not have sufficient historical data to estimate ECOG score and were given a score of 0. In total, there were 23, 16, and 3 patients categorized into the low, intermediate, and high-risk groups, respectively. These groups had non-overlapping PFS and OS curves (p

Description: Introduction: Determining the optimal post-remission management for elderly patients with acute myeloid leukemia (AML) remains a challenge. AML is primarily a disease of the elderly with 〉60% of newly diagnosed patients aged 60 years and older. For younger AML patients, post-remission therapy in the form of high-dose cytarabine (HIDAC) consolidation or allogeneic hematopoietic stem cell transplant (HSCT) is critical in maintaining durable disease control and improving survival. However, post-remission HIDAC in elderly AML patients is associated with higher rates of neurotoxicity and decreased survival benefit compared to younger patients. The optimal post-remission therapy for elderly AML patients remains undefined. The objective of this study is to determine the outcomes of using varying doses (0.25-3 g/m2) of cytarabine as post-remission consolidation therapy in an elderly AML population. Methods: We conducted a single-center retrospective analysis of AML patients aged 60 years and older treated with cytarabine as consolidation therapy at UPMC Hillman Cancer Center between January 1, 2005 and December 31, 2014. Patients were excluded if they were not in complete morphologic remission prior to proceeding with cytarabine consolidation or if they proceeded directly to HSCT after consolidation therapy. Relapse-free survival (RFS) was measured from the time of post-induction bone marrow biopsy confirming remission to the date of relapse or death. Overall survival (OS) was defined as the duration from diagnostic bone marrow biopsy confirming AML diagnosis to the date of death. Kaplan-Meier analysis was used to estimate the survival distributions and log-rank test was used to compare survival functions from groups. Multivariate analysis was performed using Cox proportional hazard regression to determine the relationship of RFS and OS to patient's age, cytogenetic risk group, AML type (de novo vs secondary AML), transplant status, cytarabine dosage and number of cycles. All data was analyzed using SAS v9.4 (SAS Institute, Cary, NC, USA). Results: Out of 156 identified patients, 121 were eligible for analysis. Median age at diagnosis was 66 years (range 59-78) with 77 (64%) male patients. Thirty-six patients (30%) had secondary AML. Cytogenetic abnormalities were favorable in 7 (6%), intermediate in 86 (71%), unfavorable in 24 (20%), and unknown in 4 (3%) patients. Cytarabine was administered at a mean dose of 1.44 g/m2 (range 0.25-3.0, SD 0.84) and a median number of cycles of 4 (range 1-4). One patient (0.8%) developed reversible grade 3 neurotoxicity during cycle 2 at a dose of 2 g/m2 with ataxia, dysmetria, and tremors. For all patients, the median RFS was 12.5 months (95% CI 9.7-15.6). Median RFS was significantly different among the cytogenetic risk groups (p=0.0008 via log-rank test): favorable-risk RFS had not been reached because most subjects were in remission and alive at time of analysis, intermediate-risk RFS 13.6 months (95% CI 11.0-17.3), unfavorable-risk RFS 8.3 months (95% CI 3.5-8.9). In this study population, the median OS was 20.5 months (95% CI 16.4-27.1). Median OS was significantly different among the cytogenetic risk groups (p=0.003 via log-rank test): favorable-risk OS 131.3 months (95% CI 12.9-upper limit not reached), intermediate-risk OS 25.1 months (95% CI 18.9-39.4), and unfavorable-risk OS 10.8 months (95% CI 10.4-15.8). Average cytarabine dose did not significantly correlate with RFS or OS in the model. Multivariate analysis revealed a 27% decreased rate of relapse (HR 0.73, 95% CI 0.58-0.92, p=0.008), and 24% decreased mortality rate (HR 0.76, 95% CI 0.59-0.96, p=0.024) with each additional cytarabine cycle given. Conclusions: Our study supports the use of cytarabine as a tolerable and effective option for post-remission therapy in elderly AML patients, particularly those with favorable-risk cytogenetics. Each additional cycle administered was associated with improved RFS and OS rates in this study population. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 304 Background: Bendamustine is a bifunctional alkylating agent that is approved for the treatment of chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma. This first multicenter, phase I/II trial investigated the combination of bendamustine, lenalidomide and dexamethasone (BLD) as a potentially effective treatment option for multiple myeloma (MM) patients, particularly for those with pre-existing or bortezomib-induced neuropathy. Our primary objective was to determine the maximum tolerated dose (MTD) and safety profile of bendamustine and lenalidomide when administered with dexamethasone for patients with relapsed or refractory MM. Methods: We conducted an open-label, dose escalation study (Table 1). Patients were enrolled from June 2008 through February 2011. Eligible patients were aged ≥ 18 years with confirmed, measurable stage II or III MM that was refractory to or progressed after 1 or more prior therapies including lenalidomide. Patients were assigned to their dose levels in a classical 3+3 cohort design. Phase I was to assess the safety and to establish the MTD of the combination treatment. The phase II portion of the study was to assess the overall response rate (ORR) at the MTD. Intravenous bendamustine was given on days 1 and 2, oral lenalidomide on days 1–21, and oral dexamethasone on days 1, 8, 15, and 22 of the 28-day cycle. Treatment was given until plateau of best response as determined by the International Myeloma Working Group uniform response criteria for a maximum of 8 cycles. The study doses were escalated through 3 levels, in a 3+3 dose escalation scheme. The MTD was defined as the dose level at which ≤1 of 6 patients experienced dose-limiting toxicity (DLT) during the first cycle of therapy when the next higher dose level was associated with DLTs in ≥ 2 patients. Primary endpoint was the MTD. After determining the MTD, up to 12 additional patients were enrolled in an MTD expansion arm to better evaluate toxicity and clinical activity. Secondary endpoints included preliminary efficacy, as evidenced by objective response, time to disease progression, and overall survival. Results: 36 patients with a median age of 63 years (range 38 to 80) were enrolled. The median number of prior therapies was 3 with a range of from 2–9; 79% of the patients had prior lenalidomide, 48% had prior thalidomide, and 34% had both. 69% of the patients had a prior autologous stem cell transplant. The MTD was 75 mg/m2 for bendamustine and 10 mg for lenalidomide. DLTs included at dose level 2: 1 grade 4 neutropenia; at dose level 3: 2 grade 4 neutropenias and 1 delayed platelet recovery from grade 3 thrombocytopenia. 25 received at least 2 cycles and were included into the response assessment. A partial response or better was observed in 52% (n=13) of the patients, including 24% (n=6) VGPR. MR was observed in 24% (n=6), SD 16% (n=4), and PD 8% (n=2). BLD induced fast responses with a time to best response of 1.6 months (range 0.7–7.4). The response was independent of prior exposure to lenalidomide evidenced by the fact that 84% of patients with VGPR/PR had prior treatment with lenalidomide. The median follow up for patients at risk of progression is 8 months (range 4–13). The estimated median progression free survival (PFS) is 4.4 months (95% CI (3.4, 9.2). 4 patients have died and the median follow up for patients who are still alive is 13 months (range 6–33). The median OS survival has not been reached yet. We did not observe any unanticipated DLTs. The only grade 4 adverse events for all patients for all cycles included 24.1% neutropenia and 7% thrombocytopenia. No infection was associated with the neutropenia and all AE resolved successfully. Conclusions: This is the first phase I/II trial testing bendamustine, lenalidomide and dexamethasone in combination for relapsed and refractory MM. This regimen is safe and well tolerated even in older patients up to 80 years. Based on the mainly myelosuppressive side effects, concomitant treatment with filgastrim is recommended. This regimen induced fast responses and high response rates even in heavily pretreated MM patients. The high responses were also achieved in patients with prior exposure to lenalidomide suggesting that BLD overcomes resistance to lenalidomide and is a highly active regimen. Disclosures: Lentzsch: Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria. Burt:Celgene Corp: Honoraria, Speakers Bureau; Cephalon: Honoraria, Speakers Bureau. Roodman:Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Agha:Novartis: Consultancy. Zonder:Millennium: Consultancy, Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Medtronics: Honoraria; Amgen: Consultancy.

Description: This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.

Description: The current standard of care for patients with newly diagnosed multiple myeloma (MM) aged less than 65 years is high-dose chemotherapy combined with autologous stem cell transplantation (ASCT) based on improved progression free survival (PFS) and overall survival (OS) compared with conventional chemotherapy. The introduction of novel agents, for example lenalidomide and bortezomib over the last decade, has substantially improved MM outcomes providing similar response rates to ASCT. As a consequence, the role of upfront ASCT has become more controversial. Therefore, this randomized clinical trial aims to determine the role of upfront ASCT in patients with newly diagnosed MM patients receiving lenalidomide and low-dose dexamethasone as induction therapy. Patients enrolled into the study were aged ≥18 years with newly diagnosed MM, transplant eligible, and meeting CRAB criteria. Patients were randomized to receive 4 cycles of lenalidomide (25 mg days 1–21) plus low-dose dexamethasone (40 mg days 1, 8, 15, 22) followed by ASCT conditioned with 200 mg/m2 melphalan (Arm A; LD+ASCT) or 8 cycles of lenalidomide plus low-dose dexamethasone (Arm B; LD alone). Both groups received lenalidomide maintenance therapy 10-15 mg for up to 2 years. Patients in both treatment arms received stem cell collection after 4 cycles of lenalidomide plus dexamethasone if at least a partial response was achieved. Patients with stable disease or progressive disease (PD) went off study. The primary objective was to compare the best response between patients treated with lenalidomide plus dexamethasone followed by ASCT and patients treated with lenalidomide plus dexamethasone alone. Secondary objectives were to compare the duration of response (DOR), PFS, and OS between the two treatment arms and to evaluate the secondary malignancies in both arms. Fifty patients with newly diagnosed MM were randomized between February 2008 and May 2013, and 47 patients were eligible for evaluation in this interim analysis; 25 patients randomized to Arm A (LD+ASCT) and 22 patients randomized to Arm B (LD alone). Overall, patients had a median age of 61.6 years (range 48–75), 60% were male, 34% ISS Stage I, 49% ISS Stage II, 17% ISS Stage III. The data were analyzed according to the IMWG response criteria (Blood. 2011 May 5;117(18):4691-5). In an intention-to-treat analysis, there was a trend towards improved overall response rate (ORR) in patients receiving LD+ASCT (96%) compared with patients receiving LD alone (77%; p=0.08) (Table 1). After a median follow-up of 36.8 months (range 1.1–62.7), the median DOR was 13.9 months (95% confidence interval [CI] 4.0–34.1) in the LD+ASCT group compared with 21.2 months (95% CI 11.0–22.9) in the LD group. Overall, 18 patients have PD (10 patients in the LD+ASCT arm and 8 patients in LD arm), and 8 patients have died (4 patents in the LD+ASCT arm and 4 patients in the LD arm). Median PFS for LD+ASCT versus LD was 17.0 months (95% CI 15.5–not estimable) versus 25.2 months (95% CI 9.0–not estimable; p=0.94). Median OS for LD+ASCT versus LD was 57.6 months (95% CI 48.0–not estimable) versus not reached (p=0.94). Two patients in the LD alone arm developed a secondary malignancy, including 1 patient with myelodysplastic syndrome (MDS) 13 months after the start of therapy. This interim analysis of an ongoing randomized clinical study comparing lenalidomide plus low-dose dexamethasone induction with and without upfront ASCT in patients with newly diagnosed MM suggests that addition of ASCT resulted in a trend towards improved ORR. This did not result in a significant difference in terms of PFS or OS between the two treatment arms. In contrast there was a trend of better DOR in the LD alone arm. The data show that LD alone can achieve similar results as LD+ASCT, however careful interpretation is required due to the low patient number and relatively short follow-up. The incidence of secondary malignancy was low, including the development of 1 MDS. Disclosures: Schecter: Celgene: Honoraria, Speakers Bureau. Mapara:Celgene: Research Funding, RO1 Other. Lentzsch:Celgene: Research Funding.