ALBERT

Description: Background: In Phase II trials, carfilzomib (Cfz) was associated with dyspnea (34%), hypertension (14%), renal insufficiency (24%), and peripheral edema (24%) with cardiac events reported in 7% of patients (pts). In order to better understand these toxicities, we prospectively instituted detailed cardiac evaluation in 62 Cfz treated multiple myeloma (MM) pts. Methods: Pts received Cfz between 8/11-5/14. Parameters recorded included Cfz dose, concurrent chemotherapy, hydration, blood pressure, day 1 and 2 creatinine, troponin and NT-proBNP, baseline and cycle 4 echocardiograms with EF, strain and compliance. Notable cardiac events were examined for attribution. Results: Median age was 65 years, with 60% male. 20 pts had no prior therapies, 42 were relapsed; mean 4 prior therapies (range 1-10). 20 received induction chemotherapy (Cfz, dex, thalidomide, cyclophosphamide). At relapse, Cfz was given alone in 21 pts, with added cyclophosphamide in 10, and with an IMiD in 10. Cfz dose was 20mg/m2 days 1,2 and ranged from 27-45mg/m2in subsequent treatment days. Dex was given at 20-40mg weekly in 77% pts. Hydration (250-500ml) was delivered in 89% of patients pre and 63% post treatment. Baseline hypertension (〉140mmHg) was present in 20% of pts and rose ≥10mmHg in 26% on day 2, but dropped ≥10mmHg in 36%. On day 8, more pts (32%) had hypertension pre-treatment. Baseline creatinine was elevated in 25% pts. 7 of 55 (13%) pts had a creatinine rise (≥0.3 mg/dL) on day 2, 5 of whom had elevation at baseline. Thus, with normal baseline creatinine and pre-treatment hydration 2/45 (4%) pts had a creatinine rise. Troponin levels on day 1 were normal in all 16 tested patients. 2/25 pts had an elevated troponin on day 2, one with associated MI on day 4. In these 2 pts, symptomatic pre-existing ischemic heart disease and severe cardiac amyloid were confounding factors. Mean baseline NT-proBNP (n=22) was elevated at 565 pg/mL (range

Description: Intro: Multiple myeloma (MM) is an incurable malignancy that arises from MGUS, however the majority of patients with MGUS do not go on to develop MM. A deeper understanding of the biology of progression from MGUS to MM is needed to identify patients at higher risk of progression and identify potential strategies to prevent development of MM. Altered bone metabolism is common in MGUS with upregulation of the receptor-activator of nuclear kB ligand (RANKL) to osteoprotegrin (OPG) ratio. Vitamin D has a central role in bone metabolism and has recently been associated with progressive disease in several malignancies, including MM. We hypothesized that progressive alterations in the key molecules of bone remodeling would correlate with the risk group of MGUS and that correction of vitamin D deficiency would lead to improved equilibrium of selective cytokines involved in bone remodeling and metabolism. Methods: 43 patients with MGUS or smoldering myeloma were assigned to low (0 or 1 risk factor) or high (2 or 3 risk factors or smoldering multiple myeloma (SMM)) risk of progression to MM based on the IMWG consensus statement (Leukemia. 2010, June; 24(6); 1121-7). We measured 25 hydroxyvitamin D levels, IL-6, and the RANKL/OPG ratio via enzyme linked immunosorbent assay (ELISA). Patients with low levels of 25 hydroxyvitamin D were treated with 6,000 units of cholecalciferol daily for 8 weeks and then 2,000 units daily thereafter. Repeat levels of 25 hydroxyvitamin D, interleukin-6 (IL-6), and RANKL/OPG were repeated after three months of cholecalciferol therapy. Results: Total enrollment was 43 patients, with 26 patients with low risk disease and 17 patients with high risk disease. There was no significant difference in IL-6, OPG, RANKL, or the RANKL/OPG ratio levels between patients with low versus high risk disease. Patients with SMM versus patients with MGUS had higher levels of IL-6 RANKL and the RANKL/OPG ratio. 14 patients were found to have vitamin D deficiency with 25 hydroxyvitamin D

Description: Background: The p53 deletion has been documented to confer poor prognosis in patients with multiple myeloma (MM) treated with either conventional chemotherapy or autologous stem cell transplant (ASCT). However, it is not clear whether primary drug resistance and/or rapid relapse account for these adverse outcomes. Objective: Evaluate the impact of the p53 deletion in patients who have undergone ASCT for MM on baseline features, response to initial therapy, progression free survival and overall survival post ASCT. Method: Retrospective review of all patients undergoing ASCT for MM at our institution from January 2000 to July 2007. Results: 31 patients with the p53 deletion intended for ASCT were identified. Four patients did not undergo transplant: 2 patients had plasma cell leukemia (PCL) and died within 4 months of diagnosis, 1 patient had primary refractory disease to all therapy and died in 1 year, and 1 patient’s stem cells could not be collected. The 28 who underwent transplant had a median age of 52 (range 30–76) and 20 (78%) were male. Immunoglobulin subtype was IgG in 14 (52%), light chain in 10 (36%), IgA in 1 (4%), IgD in 1 (4%) and non secretory in 1 (4%). 23 pts (85%) had bony disease. ISS stage was as follows: 13 (52%) stage I, 6 (24%) stage II, and 6 (24%) stage III. Seven patients presented with PCL. All patients were treated with dexamethasone based induction chemotherapy (alone or VAD), with 6 patients also receiving thalidomide. Pre-transplant status after induction therapy was 0 CR, 22 PR (92%), 1 MR (4%) and 1 SD (4%). All patients were conditioned with high dose melphalan 140–200mg/m2. There was one patient who died within 100 days of transplant. Overall responses after completion of ASCT, compared with diagnosis, in evaluable pts (n=22) included 1 CR (5%), 19 PR (86%), 2 MR (9%). Median progression free survival (PFS) for this cohort was 16.9 months (95%CI 9.1–22.3) and median overall survival (OS) was 48.2 months (95%CI 11.3–67.2) post transplant. This is considerably shorter when compared to the full cohort of MM pts transplanted at our institution during the same timeframe (n= 706): median PFS 24.4 months and median OS 76.6 months post transplant. Conclusions: Patients with the p53 deletion have a high incidence of plasma cell leukemia (29%), but most respond well to induction therapy and ASCT. However, the duration of response is short (16.9 months), nearly 8 months less than our overall results with ASCT. Furthermore, median overall survival post transplant is only 4 years, over 2 years shorter than the median of 6.4 years observed in all ASCT patients. ASCT is less effective therapy in patients with this poor prognostic marker; development of novel therapeutic regimens, including targeting p53 dysregulation pathway, may be required to improve the clinical outcome in this subset of MM.

Description: Abstract 1977 Introduction: Transplant options are limited for adult patients (pts) who lack a fully matched related or unrelated donor. We hypothesized that in-vivo T-cell depletion with r-ATG would allow safe allo-SCT from mismatched, unrelated donors, thus expanding the potential donor pool for pts with hematologic malignancies who require allo-SCT. Patients and Methods: Thirty seven adult pts (age 20 – 70, median 45) underwent a first unrelated, mismatched, allo-SCT between 1/1/2006 and 6/30/2011 at Mayo Clinic Arizona for hematologic malignancy (35 PBSC, 2 marrow). All pts had at least a one allele or one antigen mismatch (MM) at HLA-A, -B, -C, or -DRB1, and all except one pt received r-ATG as part of the GVHD prophylaxis strategy (dose range 2.5 – 10 mg/kg in daily dose of 2.5 mg/kg depending on degree of mismatch, with the last dose generally given on day −1). One pt received Campath after experiencing anaphylaxis to r-ATG. Pts were transplanted for acute myeloid leukemia (n = 19; 10 CR1, 6 CR2, 3 other), acute lymphoblastic leukemia (n = 8; 4 CR1, 4 CR〉/= 2), chronic myeloid leukemia (n = 1), myelodysplastic syndrome (n = 5), or non-Hodgkin lymphoma (n = 4). Conditioning was myeloablative in 20, reduced intensity in 16, and non-myeloablative in 1. Mismatches were as follows: 1-allele MM (n = 7); 1 antigen MM (n = 15); 2 allele MM (n = 4); 1 antigen, 1 allele MM (n = 7); and 2 antigen MM (n = 4). Additional GVHD prophylaxis included tacrolimus plus either methotrexate (n =21), mycophenolate mofetil (n = 14), or other (n = 2). Results: The median follow-up for surviving pts is 12 months. As of 6/30/11, 31 pts were alive, and 6 had died of the following causes: multiorgan failure (n = 1), relapse (n = 3), and veno-occlusive disease (n = 2). To date, there have been no deaths related to acute or chronic GVHD. The 1- and 2-year estimated rates of overall survival are 84.5%/78.8% (Fig. 1); of progression-free survival 79.7%/72.0%. The estimated rate of relapse at 1 and 2 years is 11.8%/18.7%, and of non-relapse mortality 8.1%/10.5%. Four pts (10.8%) have developed severe (grades III-IV) acute GVHD by day 100 (days 19, 27, 30, 43; one pt after withdrawal of prograf due to transplant-associated microangiopathy). No late onset severe acute GVHD has been seen. Moderate to severe NIH-defined chronic GVHD occurred in a single pt at risk (cumulative incidence estimate 2.4% at 1 year, 4.7% at 2 years; Fig. 2). Four pts have reactivated EBV, with one developing PTLD (all have been treated with Rituximab). CMV reactivation was seen in 24 pts (65%), CMV disease in 4, with no deaths directly related to CMV. Conclusions: In vivo T-cell depletion with r-ATG abrogates severe acute and chronic GVHD, and allows use of mismatched unrelated donors for allo-SCT in adult pts with otherwise incurable hematologic malignancies. Long-term survivors are generally free of severe chronic GVHD, with good quality of life. There does not appear to be an increased incidence of disease relapse, and non-relapse mortality is low. This approach is safe, effective, and considerably expands the donor pool for adult pts who require allo-SCT. Disclosures: Reeder: Celgene: Research Funding; Millennium Pharmaceuticals Inc.: Research Funding; Novartis: Research Funding. Mesa:Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding.

Description: Background: Single autologous stem cell transplant (ASCT) is considered the standard of care for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. The role of a second ASCT as salvage therapy is unclear. Method: Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results: Between March 1992 and August 2004, 28 MM pts received a second ASCT for relapsed MM at our institution. Median age was 57 years (range 39–69) at second transplant. 17 pts were male. Immunoglobulin subtype included IgG (16), IgA (8), light chain (1), nonsecretory (2) and IgM(1). Median initial albumin was 42g/l (27–48). In 15 patients in whom cytogenetic studies were available, 2 were positive for the 13q deletion. Transplant conditioning regimen for first transplant was melphalan (MEL) + TBI +/− etoposide (E) in 6, MEL alone in 15 and other regimens in 7 pts. 2nd ASCT conditioning consisted of MEL + TBI +/− E in 2, MEL alone in 25 and BU+CY in 1. Median CD34 counts were 10.96x106/L and 4.85x106/L for 1st and 2nd ASCT respectively. The median time from diagnosis to first transplant was 9 months (2–74). The median time to relapse after the first transplant was 29 months (6–85), with a median interval between transplants of 39 months (6–99). The median time to progression after the second transplant was 13 months (5–56). No transplant-related deaths occurred. At median follow-up after 2nd ASCT of 15 months (1–60), 20 (71%) pts are alive. Twelve pts (43% of all pts) are free of disease progression. The 5-year actuarial progression-free survival (PFS) and overall survival (OS) was 47% and 32%, respectively. Long term progression-free status based on the progression-free interval after 1st transplant is summarized in the following table: Interval Total number of pts Number of progression-free pts ≤ 12 months 1 0 (0%) 12–24 months 9 3 (33%) ≤ 24 months 18 9 (50%) Conclusions: 2nd ASCT is a feasible and safe salvage therapy in relapsed MM patients; 2nd ASCT is effective in providing prolonged remission over one year; 2nd ASCT is most effective in patients whose time to progression after 1st ASCT exceeds 24 months.

Description: Abstract 201 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 March 2012, we opened 6 sequential phase 2 trials and treated 345 patients with relapsed MM with pomalidomide at differing doses with weekly dexamethasone (Pom/dex). Results of 164 of these patients have been previously published. Here we describe long term follow up of these patients as well as results of an additional 181 patients with relapsed MM treated with the Pom/dex regimen. Methods: The six cohorts consisted of: Cohort 1 (N=60): relapsed MM with 1–3 prior regimens, 2 mg dose; Cohort 2 (N=34): lenalidomide (LEN) refractory, 2 mg dose; Cohort 3 (N=35): BZ)/LEN refractory, 2 mg dose; Cohort 4 (N=35): BZ/LEN refractory, 4 mg dose; Cohort 5 (N=60) LEN refractory, 1–3 prior regimens, 4 mg dose; and Cohort 6 (N=120) LEN refractory, 4 mg dose. Pomalidomide was given orally 2 mg daily or 4mg daily on days 1–28(cohorts 1–5) or 1–21 (cohort 6) 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 deep venous thrombosis (VTE) prophylaxis or full dose anticoagulation. Results: A total of 345 patients were enrolled across all 6 cohorts. One patient was ineligible and excluded from analysis. The median age was 64 years (32–88). The median time since diagnosis was 53 months. The median number of prior therapies was 3 (1–14). 147 (44%) had high-risk molecular markers by mSMART criteria. Prior therapies consisted of thalidomide 52%, lenalidomide 87%, bortezomib 75%, autologous stem cell transplant 70% and allogeneic transplant 3%. The median follow-up is 10.4 months (5.4–34 months). Sixty-seven percent are alive and 32% remain progression free. 46 patients are continuing to receive treatment. The most common toxicities (grade 3 or higher) were neutropenia (31%), anemia (16%), thrombocytopenia (12%), pneumonia (8%) and fatigue (8%). VTE was seen in 10 patients (3%). Outcomes are shown in Table 1. Across all 6 cohorts confirmed responses of partial response (PR) or better were seen in 34%. The response rate in all patients with mSMART high risk status was 30.6%. Responses and duration of response (DOR) in those with high risk molecular markers include: 17p– 19 of 56 (34%) DOR 8.2 months; t(4;14) 6 of 24 (25%) and DOR 4.8 months; t(14;16) 7 of 11(64%) and DOR 9.5 months; deletion 13 by cytogenetics 13 of 37 (35%) with DOR 8.2 months. In a multivariate analysis, only LDH 〉 ULN, number of prior regimens, and prior BZ therapy were predictive of a shorter TTP and factors associated with a poor OS following initiation of pomalidomide therapy included B2M 〉 5.5, LDH 〉 ULN,number of prior regimens, and prior BZ therapy. Conclusions: Pom/dex is active and well tolerated even in heavily pretreated patients and those with high risk molecular markers. Remissions are durable. Response rates and toxicity are similar between the 2 mg and 4 mg doses. Disclosures: Lacy: Celgene: Research Funding. Stewart:Celgene: Consultancy, Honoraria. Reeder:Celgene: Mayo Clinic receives funding from Celgene to support clinical trials Other, Research Funding.

Description: 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

Description: Abstract 3884 Poster Board III-820 Background and Objective Thalidomide/dexamethasone (thal/dex) combination has shown high activity in newly diagnosed multiple myeloma (MM) (Rajkumar SV. at al, J Clin Oncol 2006;24:431-436). In newly diagnosed patients, lenalidomide/dexamethasone (len/dex) has demonstrated superiority compared with high-dose dexamethasone alone (Zonder JA et al, Blood 2007;110:77). Although both thal/dex and len/dex are active in newly diagnosed MM, no randomized trial has been reported comparing these two regimens, and unfortunately none are ongoing or planned. We compared the efficacy and the toxicity of thal/dex and len/dex as primary therapy in 411 newly diagnosed MM patients treated at the Mayo Clinic. Patients and methods 411 consecutive patients seen at Mayo Clinic between 2001 and 2008, who received induction with thal/dex (n=183) or len/dex (n=288) were retrospectively studied. Thalidomide was given at a dose ranging from 100 mg/day to 400 mg/day continuously; the lenalidomide dose was 25 mg/day, days 1-21 on a 28-day cycle. All patients received dexamethasone, either at high-dose (40 mg orally on days 1-4, 9-12, and 17-20) or at low-dose (40 mg orally day 1, 8, 15, 22); each cycle was repeated every 4 weeks. In addition, a case-matched subgroup analysis that adjusted for age, gender and transplantation status was performed among patients who received high-dose dexamethasone comparing the thal/dex (n=72) and len/dex (n=72) groups. Outcome was analyzed on an intention-to-treat basis. The Chi-square or the rank sum tests were used to compare variables. Time-to-event analysis was performed using the Kaplan-Meier method and all comparisons were determined by the log-rank test and by the Cox proportional hazards model. Results On intention-to-treat analysis, of 411 patients, 80.3% versus 61.2% patients, respectively in the len/dex group and in the thal/dex group (p 〈 0.001), achieved at least a partial response. A significant difference between the 2 groups was found in terms of both very good partial response or better (34.2% vs 12.0%, p 〈 0.001) and complete response rate (13.6% vs 3.3%, p 〈 0.001). Duration of therapy was significantly longer in len/dex patients as compared to thal/dex patients: 36.7% vs 12.6% of patients who did not stop treatment to receive SCT were still receiving therapy at 1 year (p 〈 0.001).Time-to-progression was significantly better in the len/dex group than in patients receiving thal/dex (median 27.4 vs 17.2 months, HR 0.64; 95% CI 0.44-0.93; p = 0.019). Similarly, progression-free-survival was significantly higher in len/dex patients (median 26.7 vs 17.1 months, HR 0.69; 95% CI 0.48-0.98; p = 0.036). This translated into an increase in overall survival (OS) (median not reached for len/dex group compared to 57.2 months in thal/dex patients, HR 0.60; 95% CI 0.40-0.92; p = 0.018). Survival advantages were evident in patients presenting with International Staging System Stage (ISS) I/II (HR 0.57; 95% CI 0.32-1.00; p = 0.052) at diagnosis but not in patients with ISS stage III in subgroup analysis. There was a trend toward better OS in len/dex group compared to thal/dex group both for patients who underwent transplant and for patients who did not. A similar rate of patients experienced at least one grade 3 or higher adverse event (57.5% vs 54.6% in len/dex and thal/dex groups, respectively, p = 0.568). However, the toxicity profile was different in the two groups: major grade 3-4 toxicities of len/dex were hematological, in particular neutropenia (14% with len/dex vs 0.6% with thal/dex, p

Description: Background: Studies have shown ASCT to be feasible in MM patients (pts) with renal impairment but there are limited data supporting this approach in pts with severe dialysis-dependent renal failure. Patients and Methods: This is a single institution retrospective review of all MM pts who were receiving regular dialysis support at the time of ASCT. Pts with light chain amyloidosis were excluded. Results: From 1998–2006, 22 hemodialysis patients underwent ASCT at our institution. Median age at transplant was 54.3 years (range, 39.4–64.7); 17(77%) pts were male; 17(76%) Salmon Durie stage II–IIIB . MM subtypes: light chains only 9(41%), IgG 8(36%), IgA 4(13%), IgD 2(9%). All pts received high-dose dexamethasone (DEX)-based induction therapy (VAD or DEX alone). High dose therapy consisted of Melphalan (MEL) 200 mg/m2 in 18 pts and MEL 140 mg/m2 in 3 pts. A median of 5.87 X 106 (range, 2.47–51.0) CD34+ cells/kg were collected using cyclophosphamide 2.5 g/m2 + GCSF 10ug/kg/day. Median days to discharge were 19 (range, 14–59). Hematologic toxicity: Of 20 pts with transfusion data available, 14(70%) required RBC and 18(90%) platelet transfusions. Median time to engraftment for neutrophils was 11 days (range, 9–14) and for platelets 13 days (range, 8–17). All patients developed febrile neutropenia. Non-hematologic toxicity (data available in 21 pts): cardiac 13(62%) (arrhythmias, myocardial infarction, CHF), hypotension 6(29%), neurologic 6(29%)(seizure, altered sensorium), infections 6(29%), diarrhea 6(29%), electrolyte imbalances 4(19%) and bleeding 3(14%). Most common grade 3–4 toxicities included mucositis 17(81%), cardiac 12(57%)(most due to atrial arrhythmias), bleeding 3(14%)(epistaxis, hematemesis, tissue hematomas) and infections 3(14%)(CMV, bacteremia, Candidemia). Transplant related mortality (TRM) was 13.6% (3/22) with causes of death including disseminated candidiasis (2) and CMV infection. Responses: Partial responses (PR) were achieved in 18/22 pts. Progression free survival (PFS) from transplant was 22.3 months (95% CI 15–45.6). Three pts (13%) became dialysis-independent (all within 30 days post-transplant). At a median follow-up of 29.6 months (range 0.8–79.6), 10/22 (45%) of patients are alive. Estimated median overall survival from date of transplant was 60 months (95%CI 20.2–79.6) with a 5-year survival probability of 53.2%. Discussion: ASCT in dialysis-dependent MM pts achieves response rates and survival data comparable to that of non-dialysis populations. However, it carries increased toxicity, prolonged median days to discharge (19 days vs. institutional mean of 14 days) and a higher TRM (13.6% vs. institutional mean of 1.6%). The higher rates of cardiac and neurological toxicities enforce the need for pre-transplant identification of pts with co-morbidities, for consideration of dose reduction and risk factor optimization.

Description: Background: Single autologous stem cell transplant (ASCT) is considered the standard of care for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. As more options, such as biological therapy, are available to treat relapsed disease, the role of a second ASCT as salvage therapy is unclear. Method: Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results: Between February 1997 and June 2007, 61 MM pts received a second ASCT for relapsed MM at our institution. Median age was 56 yrs (range 35–71) at second transplant. 37 pts (61%) were male. Immunoglobulin subtype included IgG (36), IgA (14), light chain (6), nonsecretory (3), IgM(1) and IgD (1). Transplant conditioning regimen for first transplant was high dose melphalan (MEL) 140–200 mg/m2 in 51, MEL/etoposide(E)/TBI in 4, and MELl/TBI in 2. 2nd ASCT conditioning consisted of MEL + TBI +/− E in 2, MEL alone in 58 and Busulfan/Cyclophosphomide in 1. The median time from diagnosis to first transplant was 9.7 months (2.0–74.2). The median time to relapse after the first transplant was 32.6 months (9.7–85.6), with a median interval between transplants of 45.1 months (19.7– 115). Two transplant-related deaths occurred (3%). Response to first transplant was 4 CR (8%), 34 PR (68%), 2 MR (4%) and 10 SD (20%). Nineteen pts went on to maintenance therapy between transplants. Response to second transplant was 4 CR (8%), 41 PR (80%), 5 SD (10%) and 1 PD (2%). Median progression-free survival (PFS) was 15.8 months (0–63.8) while median overall survival (OS) was 4.2 years (0–7.0) after 2nd ASCT. The relationship between progression-free interval after 1st ASCT and the outcome of the 2nd ASCT is summarized Table 1. Patients can be stratified into two groups, those with a disease free interval of less than or greater than 24 months. The use of maintenance therapy did not differ between the two groups, 6 (40%) in patients with PFS ≤24 months and 13 (28%) in patients with PFS 〉24 months. Conclusions: 2nd ASCT is a feasible and safe salvage therapy in patients with relapsed MM. 2nd ASCT is effective in providing a median progression free survival of 1.25 years and median overall survival of 4.2 years after 2nd ASCT - results that compare favourably with other salvage approaches. Patients with a longer disease free interval after 1st ASCT experience a better progression free survival and overall survival after 2nd ASCT. It is reasonable, therefore, to consider a 2nd ASCT if the time to progression is greater than 2 years after first ASCT. Outcomes Based on Time to Progression Post 1st ASCT PFS post 1st ASCT # of pts median PFS post 2nd ASCT PFS post 2nd ASCT1 Median OS post 2nd ASCT OS post 2nd ASCT2 1 p〈 0.005, 2 p〈 0.05 ≤24 months 15 12.7 months 1 year: 46% 3.5 years 1 year: 85% 2 year: 11% 2 years: 76% 3 years 0% 3 years: 63% 4 years: 31% 〉 24 months 46 19.8 months 1 year: 74% 5.9 years 1 year: 91% 2 year: 45% 2 years: 82% 3 year: 31% 3 years: 65% 4 years: 55%