ALBERT

Description: Introduction: Filgrastim is widely used for mobilizing CD34+ cells into the peripheral blood that are easily collected by apheresis for allogeneic transplantation. With case reports documenting splenomegaly with life-threatening complications in normal donors, we prospectively evaluated spleen size using ultrasonography and clinical examination during PBPC mobilization and collection in a single-arm trial. Methods: Subjects ≥18 yrs eligible to be PBPC donors per institutional guidelines enrolled. Splenic assessments were done before, during, and after PBPC mobilization. Filgrastim dose and schedule and leukapheresis (LK) procedures were per institutional practice. The primary endpoint was fold change from baseline in splenic volume in post-baseline measurements during mobilization (measured by ultrasound [US]). Spleen size by US was measured in 3 dimensions similarly by all centers: longitudinal (craniocaudal), transverse, and diagonal (perpendicular to transverse in transverse image) diameters. Splenic volume was estimated by taking the cross-product of 3 dimensions and multiplying by 0.52, approximating the volume of an ellipse. Physical examination was performed on US days, assessing spleen palpability. US and palpation results were blinded from each other at assessment times. Timepoints included baseline (before first filgrastim dose), first LK (done before LK, typically day 4 or 5 of filgrastim), 2 and 4 days after first LK, and 7 days after last LK. Timepoints in the post-amendment cohort (n=219) were reduced to facilitate enrollment and were baseline and day of first LK (before LK). Results: 309 donors enrolled, median age 44yrs (range 18 to 74), 56% male. Mean daily filgrastim dose was 11.4mcg/kg (SD=3.0). Median number of LK was 1.5 (range 1 to 4). In all donors, the median increase in each measured dimension on first LK day was 1.4cm, 1.4cm, and 0.6cm (12.8%, 12.6%, and 15.0%), and the median fold volume increase from baseline to first LK was 1.47, resolving to near baseline 1 week after last LK. There was no apparent relationship between volume fold change and filgrastim dose, ANC, or CD34+ yield. Of 861 splenic palpation assessments reported in all donors, 98% were reported as nonpalpable (842 assessments), and 2% were palpable (19 assessments, 2 at baseline). Reporting of palpable spleens did not correlate with increased spleen size. Tenderness or guarding upon splenic palpation was reported in 2 donors with a spleen considered palpable and in 6 donors with nonpalpable spleens. No donor experienced a splenic rupture. Adverse events related to filgrastim were generally mild to moderate. Conclusion: During PBPC mobilization with filgrastim in normal donors, the spleen increased a median of approximately 50% from baseline to day of first LK and returned to near baseline 1 week after last LK. Size change was not associated with significant clinical sequelae. Timepoint Median fold change from baseline in splenic volume (Q1, Q3) *statistically significant (p

Description: Background: Oprozomib (OPZ) is a selective oral proteasome inhibitor that binds selectively and irreversibly to its target. In a phase 1b/2 study of single-agent OPZ in patients (pts) with hematologic malignancies, OPZ has shown promising antitumor activity in pts with multiple myeloma (MM) (Savona, ASH 2012, 203; Kaufman, EHA 2013, P223; Ghobrial, ASH 2013, 3184). This multicenter, single arm phase 1b/2 study evaluates the safety and tolerability of OPZ with dexamethasone (DEX) in pts with relapsed and/or refractory MM. Initial results from the study are presented. Methods: This is an open-label, phase 1b/2 study (NCT01832727). Pts with relapsed and/or refractory MM who have received 1–5 prior lines of therapy (at least 1 regimen including lenalidomide and/or bortezomib) are eligible for enrollment. Pts are receiving OPZ on days 1, 2, 8, and 9 of a 14-day cycle (2/7 schedule) or on days 1–5 of a 14-day cycle (5/14 schedule). The starting OPZ dose was 210 mg on both schedules. Doses are being escalated in 30-mg increments using a standard 3+3 dose-escalation scheme. DEX (20 mg) is being given by oral administration on days 1, 2, 8, and 9 of a 14-day cycle. Treatment is being administered until pt withdrawal or progressive disease. The primary objectives of the phase 1b study are to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of OPZ with DEX and to evaluate safety and tolerability. Response is being assessed by IMWG criteria, with inclusion of minimal response and near complete response by modified EBMT criteria to provide an overall response rate (ORR) as reflected by partial response (PR) or better and a clinical benefit rate (CBR) as reflected by minimal response (MR) or better. Results: As of July 7, 2014, 29 pts were enrolled (2/7 schedule, n=14; 5/14 schedule, n=15). Median age was 64 years (2/7 schedule) and 63 years (5/14 schedule). Pts received a median of 3 prior regimens in the 2/7 schedule and 2 prior regimens in the 5/14 schedule. Preliminary median OPZ treatment duration in this ongoing study was 13.3 weeks in the 2/7 schedule (range, 3.3–35.3 weeks) and 5.7 weeks in the 5/14 schedule (range, 0.1–24.7 weeks). No dose-limiting toxicities (DLTs) have occurred in pts on the 2/7 schedule; 3 DLTs were observed on the 5/14 schedule (210 mg cohort; grade 2 subarachnoid hemorrhage, grade 3 transaminitis, and grade 4 thrombocytopenia [n=1 each]). In both treatment schedules combined, the most common adverse events (AEs) were diarrhea (83%), nausea (79%), and vomiting (62%); additional AEs are shown in the table. The most common grade 3 AEs included diarrhea (21%), anemia (14%), pneumonia (14%), and nausea (10%). Grade 4 AEs included thrombocytopenia (n=1, 2/7 schedule; n=2, 5/14 schedule) and decreased lymphocyte count (n=1, 5/14 schedule). Grade 5 sepsis occurred in 1 pt on the 2/7 schedule (240 mg/d) and 1 pt on the 5/14 schedule (210 mg/d). Treatment was discontinued because of AEs in 2 pts on the 2/7 schedule and 7 pts on the 5/14 schedule. Five pts on the 2/7 schedule and 7 pts on the 5/14 schedule had their OPZ dose reduced at least once. In 12 pts enrolled on the 2/7 schedule who had ≥2 assessments for response, 5 pts had a PR, 2 pts had a MR, and 5 pts had stable disease (SD) as their best overall response for an ORR of 41.7% and a CBR of 58.3%. In 7 pts enrolled on the 5/14 schedule who had ≥2 response assessments, 3 pts had a MR and 2 pts had SD as their best overall response for a CBR of 42.9%. Conclusions: Preliminary results suggest that treatment with OPZ and DEX has improved gastrointestinal tolerability in pts with relapsed and/or refractory MM relative to single-agent OPZ (Savona, ASH 2012, 203; Kaufman, EHA 2013, P223; Ghobrial, ASH 2013, 3184). Additional measures will be taken to improve gastrointestinal tolerability. Encouraging responses have been seen in this heavily pretreated patient population, especially with the 2/7 schedule. Enrollment in the phase 1 portion of the study is ongoing; dose escalation will continue until the MTD and RP2D are determined. Updated results will be presented at the meeting. Disclosures Hari: Genzyme: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Shain:Onyx/Amgen: Speakers Bureau. Voorhees:Millennium/Novartis: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Research Funding; Prolexys Pharmaceuticals: Research Funding; Acetylon: Research Funding; Janssen: Research Funding; GSK: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Abidi:Onyx: Speakers Bureau. Zonder:Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria. Richardson:Onyx: Membership on an entity's Board of Directors or advisory committees. Neuman:Onyx Pharmaceuticals: Employment. Dixon:Onyz Pharmaceuticals: Employment, Equity Ownership.

Description: Following up on single institution studies suggesting that engaging patients in exercise and/or stress reduction techniques during hematopoietic cell transplantation (HCT) improves functional status and quality of life, we conducted a randomized study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). METHODS: Patients (n=711) at 21 US centers provided symptom and quality of life data at enrollment. They were randomized to 1 of 4 groups using a 2x2 factorial design, stratified by center and transplant type. Prior to HCT, each group received a 15 minute stress management training session or a 15 minute exercise training session, both, or neither, with trained personnel to discuss the importance of managing stress and/or keeping active during HCT. The 3 intervention groups were also given a DVD, pamphlet and diary to track participation in exercise and/or stress management. The trainer reviewed the goals of practicing the intervention, proper technique, identification of barriers and plans to overcome them. Exercise training also included calculation of target heart rate. The exercise goal was walking 3-5 times a week for at least 20-30 minutes at 50-75% of estimated heart rate reserve. The stress management goal was to use paced abdominal breathing, progressive muscle relaxation with guided imagery, and coping self-statements to decrease stress. The interventionists re-contacted patients at 30 and 60 days after HCT to review the training goals, discuss barriers and provide encouragement. The fourth group was a usual care control group. All groups received a DVD of general information about HCT. Participants provided self-reported assessments at 30, 60, 100 and 180 days after transplant. The primary endpoints were the physical (PCS) and mental (MCS) component subscales of the SF36 at day 100. The study was designed to have 85% power to detect a difference of 0.5 STD in the exercise or stress management groups on each of the two endpoints, maintaining an overall type I error rate of 0.05. Primary analysis was on an intention to treat (ITT) basis with values assigned to patients who died or otherwise did not provide information. Enrollment occurred from January 2011-June 2012. Results The groups were well-balanced for baseline characteristics. There were no differences in the primary endpoints of PCS and MCS at day +100 among any of the groups based on the ITT analysis (Table). Results were similar using other conditional and imputed methods. Higher PCS at day +100 was associated with higher PCS at enrollment (p

Description: Abstract 3223 Poster Board III-160 There are concerns that prolonged exposure to lenalidomide (len) impairs the peripheral blood progenitor cell (PBPC) yield in patients (pts) undergoing autologous peripheral blood stem cell transplant (ASCT) for multiple myeloma. To evaluate the effect of len on PBPC yield, we retrospectively analyzed 144 consecutive pts undergoing PBPC harvest prior to ASCT for multiple myeloma between July 1, 2007 and June 30, 2009. Exclusion criteria included prior ASCT or prior treatment with an alkylating agent. Of the evaluable patients, 67 pts received at least one cycle of len as part of their pre-harvest therapy (median # of cycles 4 (range 1-28)) and 63 received non-len containing regimens. Median age for all pts was 57 years and was similar between the two groups. Initial PBPC harvest was unsuccessful (defined as collection of

Description: Abstract 2401 Background: Melphalan (M) 200 mg/m2 is a standard conditioning regimen for myeloma patients (pts) with normal renal function (NRF) undergoing ASCT. M exhibits a steep, log-linear dose effect with a potential for dose escalation (DE) to overcome M resistance. However, severe oral mucositis (OM) at M ≥ 200 mg/m2 precludes DE due to significant morbidity. Palifermin (P) as a cytoprotective agent has demonstrated efficacy in reducing intensity and duration of OM in pts receiving intensive chemo-radiotherapy. We designed a phase I study to determine the MTD of M in pts with NRF when used with P. Study Design: We enrolled 19 pts from 07/2007 to 09/2009. Data is reported on 18 evaluable pts as 1 pt was removed due to the inability to receive all 6 doses of P. DE was done (3 pt cohorts) in 20 mg/m2 increments, depending on the dose limiting toxicities (DLT). Level (L) 1 began at M 200 mg/m2 with P 60 mcg/kg/d, given as I.V. bolus on Day -5, -4, -3 and Day +1, +2 and +3 (PBSCs infused on Day 0). M was given on D-2 up to and including 280 mg/m2 (n = 6). If no symptomatic grade ≥ 3 DLTs were noted by day +30, an additional cohort of 3 pts were entered at the next dose level. Dose escalations were to stop if ≥ 2 DLTs occurred at M dose; with that dose declared as the MTD. Grade 3/ 4 diarrhea and ≥ grade 3 cardiac toxicity was considered DLT; grade 3/4 hematological toxicity was acceptable. The grade of OM was assessed daily according to the WHO oral-toxicity scale (grade 0–4). Key Eligibility Criteria: age 18–74 years, stage 2/3, ECOG performance status 〈 2, CrCl 〉 60, total bilirubin ≤ 1.5 × IULN, ALT/AST ≤ 3 × IULN, eligible for ASCT per institutional criteria and at least 2.0 × 106 CD34+ cells/kg cryopreserved for ASCT. Calculation of M dose: M dose was calculated using the actual body weight except when the actual body weight was 〉 40% above the ideal body weight; in that case, adjusted body weight was used. Results: Med age 48.5 y (33-65). Med # of prior Rx: 2 (1-5). Median CD34 cells dose 4.77 × 10(6) [2.18-11.36]; median day of neutrophil recovery +10 (10-13) and median day of platelet engraftment 19.5 (0 to 29). The overall incidence of OM ≥ grade 3 was 44% (8/18) with a median duration of OM 10 days (4 -20 d). Only 1 pt in L 1 group developed grade 4 OM. Two out of 6 pts given M 280 mg/m2 did not develop any OM. Atrial fibrillation occurred in 1/6 pts treated with M 280 mg/m2. The most common adverse events included rash (18 events, no grade 3), elevation of amylase (10, 4 grade 3-asymptomatic) and lipase (5, 2 grade 3 -asymptomatic) and edema (11, no grade 3). 11 pts (61%) required IV opioid analgesics; none needed TPN/NG feeding. All 18 pts were evaluable for response at D+100 and there were no treatment-related deaths. Median duration of follow up is 17.5 months (5.6-36.5). At D+100, all 18 patients were progression free. At D+365, 13 pts are free of progression, 2 have PD, and 2 have expired while 1 pt has not reached D+ 365 yet. First expired pt on L5 relapsed at 5 months post ASCT and no further details are available on two other expired patient. Conclusions: Palifermin permits dose escalation of M up to 280 mg/m2 with acceptable toxicity. A phase 2 trial is planned to better delineate the anti-myeloma efficacy of this regimen. Disclosures: Abidi: Millennium: Speakers Bureau. Off Label Use: Bortezomib is currently not approved for maintenance therapy after Autologous stem cells transplant. Lum: Transtarget Inc: Equity Ownership.

Description: Abstract 2241 Poster Board II-218 Introduction: T-LGL has the phenotype characteristics of a post-thymus mature T cell. Expansion of T-LGL has been reported to occur in association with viral infections, autoimmune diseases, lymphoproliferative malignancy and HSCT. The clinical significance of finding T-LGL expansion post HSCT is unclear. We recently reviewed the incidence of T-LGL expansion in patients who underwent allogeneic HSCT in our institution. We specifically asked whether T-LGL expansion was associated with increased viral infections, stable chimerism, graft-versus-host disease (GvHD), recurrence of primary disease, and overall survival. Patients and Methods: A retrospective analysis was done on all adult patients who underwent allogeneic HSCT at the Karmanos Cancer Institute between January 1, 2004 to June 30, 2009. In patients with persistent lymphocytosis (〉3000 cells/mm3) post HSCT, expansion of T-LGL phenotype was identified by flow cytometry (CD2, CD3, CD5, CD7, CD8 and CD57 positive) and clonality was confirmed by T cell receptor beta and/or gamma gene rearrangement (TCR-GR) using southern blot analysis and polymerase chain reaction (PCR). Results: A total of 547 patients underwent allogeneic HSCT during the study period. We identified T-LGL expansion in 24 patients with persistent lymphocytosis using flow cytometry. Median age of patients with T-LGL expansion was 50 years (range 24-68 years). Median time to diagnosis was 275 days post HSCT (range 69-1454 days) and median duration of follow-up was 811 days (range 85-1701 days). All 24 patients achieved full donor chimerism post transplantation by STR analysis. Fourteen out of 24 patients with T-LGL expansion had positive TCR-GR, in 2 patients TCR-GR was not done and the remainder was negative. Twenty out of 24 patients had cytomegalovirus (CMV) viremia confirmed by PCR before the onset of T-LGL expansion; the remainder had no CMV viremia. In all patients with T-LGL expansion there was no subsequent recurrence of CMV viremia or infection. All 24 patients had documented graft versus host disease (GvHD). In the group with T-LGL expansion only 2 patients relapsed with primary disease and only one patient died (due to a cardiac event). The cumulative incidence of T-LGL expansion was 4.4% at the end of the study period. Conclusion: To our knowledge, this is the largest reported series of T-LGL expansion post allogeneic HSCT. T-LGL expansion was associated with an interesting sequence of CMV viremia preceding T-LGL expansion and subsequent lack of recurrence of CMV viremia or infection. We also observed a very low number of relapse of primary disease or death in patients with T-LGL expansion. One hypothesis is that T-LGL expansion may be a result of specific stimulation with CMV antigens post allogeneic HSCT. An alternate hypothesis is that T-LGL expansion is a surrogate marker for accelerated immune reconstitution. At present, it is also unclear if T-LGL expansion is a marker of ‘graft-versus-leukemia' effect with respect to relapse of primary disease warranting further research. Disclosures: Lum: Transtarget Corporation: Founder

Description: Abstract 4551 Background: Acute graft versus host disease continues to affect approximately 60% of patients undergoing UHSCT, with significant mortality and morbidity. Methods: We prospectively evaluated the efficacy of combining Thymo (4.5 mg/kg divided doses on days -1,-2, and -3), tacrolimus and sirolimus in preventing aGVHD. The cumulative incidence (CI) rate of grade II-IV aGVHD was calculated using death without grade II-IV aGVHD and relapse as competing risks (Cr). The Cr: for non relapse mortality (NRM) CI was death due to relapse, for relapse CI was death without relapse, for chronic GVHD CI was relapse & non relapse mortality without cGVHD. Kaplan-Meier method was used to calculate overall (OS) and progression free survival (PFS). The incidence of infections and other complications were reported with the Wilson's 95% Confidence Interval (in table below). Results: Between August 2008 and November of 2010, we enrolled 47 patients (pts) with median age of 50(20–70) years. The Median follow-up time is 23.6 months (18.8–27.9). There were 21 AML, 10 MDS, 4 ALL, 2 CML, 2 CMML, 1 CLL, 3 Myelofibrosis, 2 multiple myeloma, 2 NHL. Preparative regimens included Bu/Flu 30, Bu/Flu-TBI 10, VP16/TBI 3, R-BEAM 1, and Flu/MEL-TBI 3. All pts received peripheral blood stem cells mobilized with G-CSF. Median CD34+ dose was 7.31×10 6/kg (1.9–18.6). Median donor age was 32.6 (19.0–61.0) years. All patients received daily G-CSF starting day +6 till engraftment. Twenty two pts received 8/8 and 25 received 7/8 HLA matched grafts respectively. All patients' engrafted, with median day of 11 (9–15). Twenty deaths occurred throughout the whole follow up period, due to: relapse 6, aGVHD 4, cGVHD 2, sinusoidal obstruction syndrome (SOS) 2, bleeding 1, multi organ failure 2, sepsis 2 and pneumonia 1. Twelve patients experienced disease relapse. Fourteen patients had non-relapse mortality. Twelve pts developed Grade II-IV aGVHD, 5 grade II, 4 grade III, and 3 grade IV. The CI rate for grade II-IV aGVHD at 200 days post transplant is 0.23.4% (12.4, 36.3); CI of NRM at day 1057 is 31.9% (18.4, 46.2). CI of relapse at day 1057 is 30.4% (15.2,47.1). CI of cGVHD at day 890 is 40.2(21.5, 58.2), with total of 16 cases: 8 mild, 7 moderate and one sever based on NIH consensus criteria. Median PFS is 17.7 months. PFS at 6 months is 63% and 54% at 1 year. Median OS has not been reached. OS at 6 months is 73%, and 65% at one year. The incidence of infections and other transplant related morbidities are shown in the table below. There were 2 cases of thrombotic thrombocytopenic purpura (TTP) before day 100. 16 CMV by PCR, 10 EBV by PCR, 9 HSV, 10 BK cystitis, 31 bacterial infections, 4 oral candidiasis, and 3 SOS. Conclusion: These early results suggest that the combination of Thymo, tacrolimus and sirolimus in pts undergoing UHSCT is well tolerated and is associated with a low rate and severity of acute GVHD. Disclosures: Al-Kadhimi: Genzyme Pharmaceuticals: Research Funding. Off Label Use: The use of thymoglobulin, Sirolimus and Tacrolimus in blood and marrow transplant. Lum:Transtarget Inc: Equity Ownership, Founder of Transtarget.

Description: The concept of suppressing dendritic cells (DCs) to prevent graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) has been rejuvenated since the introduction of proteasome inhibitors into clinical practice. Although early post-transplant administration of proteasome inhibitors ameliorates GvHD, delayed administration has been associated with alloreactivity-dependent gastrointestinal toxicity. This phenomenon is associated with a surge in interleukin-1β (IL-1β) and acceleration in donor T cell expansion. To address this issue, we sought to investigate whether in vivo depletion of donor T cells by concomitant administration of post-transplant cyclophosphamide (C) could overcome this phenomenon. Ten-week old BALB/c mice were irradiated (10 grays in two fractions) on day -1 and transplanted with 5x106 BM cells from C57BL6 mice. GvH inocula consisted of 5x106 splenocytes from C57BL6 (some post-CFSE labeling) or B6;FVB-PtprcaTg(CAG-Luc,-GFP)L2G85Chco Thy1a/J (ubiquitously transgenic for firefly luciferase for bioluminescence imaging (BLI). All mice were purchased from Jackson Laboratory and kept in a pathogen-free environment. Mice were untreated or received ixazomib (Z) (30μg, subcutaneously) on days -1, +2, and +5, C (1 mg intraperitoneally) on day +2, or both Z and C according to the same schedule. Mice were monitored for weight, GvHD score, and survival or sacrificed on day +6 for cytokine measurement and splenic cell counts. For BLI, mice receiving transgenic splenocytes were injected with 150mg/kg of D-Luciferin intraperitoneally and imaged 25 minutes later. GvHD worsening and sudden death occurred in a fraction of mice receiving Z following day +5 injection. The phenomenon was completely prevented by the addition of C. Overall, the group receiving both Z and C had significantly improved weight, GvHD score, and survival when compared to the mice left untreated or receiving either drug alone (figure 1). The addition of C to Z prevented IL-1β increase, was associated with suppression of tumor necrosis factor α (TNFα), and resulted in a profound depletion of splenic total and donor CD4+ cells. Furthermore, proliferating cells (CFSE low) were preferentially depleted as opposed to quiescent cells (CFSE high). BLI imaging showed an increase in signal intensity shortly after the administration of Z on day +5. On the other hand, the mice receiving C in addition to Z exhibited significantly lower donor T cell proliferation when compared to the other groups (figure 2). These findings suggest that C can prevent the phenomenon of GvHD acceleration associated with the extended administration of proteasome inhibitors, suppress cytokine production, and effectively reduce splenic total and donor CD4+ cell expansion with preferential depletion of proliferating as opposed to quiescent cells. The combination of Z and C seems a promising duplet for the prevention of GvHD. When Z is administered late following allogeneic HSCT for the prevention of disease relapse, the addition of C should be considered in order to avoid any unwanted aggravation of alloreactivity. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: Background: Bortezomib has become an integral part of front-line therapy of multiple myeloma in a large majority of patients. There are preliminary reports which show that addition of bortezomib can augment the peripheral blood CD34 count during stem cell mobilization. In this single center prospective trial we added bortezomib to G-CSF to evaluate the effects of bortezomib on peripheral CD34 counts and collection. Methods: Patients aged 18-70 years with diagnosis of multiple myeloma (MM) or non-hodgkin's lymphoma (NHL) who were eligible for autologous stem cell transplantation (ASCT) and had received no more than three prior chemotherapeutic regimens were eligible for the study. Patients were enrolled in two groups. Group A (N=3) received G-CSF 16mcg/kg for 5 days and proceeded to stem cell collection on D5 and then received bortezomib 1.3mg/m2 on D5 after stem cell collection and G-CSF 16mcg/kg on D6, 7, 8 and repeat stem cell collection on D6, 7, 8 till the goal was achieved. Group B (N=17) received G-CSF 16mg/kg on D1-5 and received bortezomib 1.3mg/m2 on D4 and proceeded to stem cell collection on D5. If the patient was not able to collect the predefined goal CD34, G-CSF was continued on D 6, 7, 8 and a second dose of bortezomib 1.3mg/m2 was given on D7. Mobilization procedure was stopped once the predefined goal CD34 collection (4 x 106/kg for MM and 2 x 106/kg for NHL) had been collected. Primary objectives of the study was to determine if addition of bortezomib to G-CSF will result in an increase in PBSCs by 〉 2-fold and to achieve median neutrophil engraftment 12 days post ASCT. Secondary objectiveswere to evaluate the collected product for co-mobilization of lymphoma or myeloma cells and to determine if the use of bortezomib increases the mobilization of immune-stimulatory Dendritic cell (DC) -1 subsets. Results: A total of 23 patients were enrolled and 20 were evaluable for the results. Only one patient with NHL was enrolled and rest had MM. Median age of pts was 57 years, M/F 8/12, median number of previous chemotherapy regimens was 1 (range 1-3). The median peripheral blood CD34 count pre and post bortezomib in all patients were 28.8 x 106/kg and 37 x 106/kg respectively. All three patients in group A had drop in peripheral blood CD34 counts on D6 post bortezomib as they had undergone stem cell collection on day 5. In part B (N=17), 15 patients had increase in peripheral blood CD 34+ve cell counts with 4 patients achieved doubling while 11 pts had less than doubling of peripheral blood CD34 count after receiving bortezomib. Two patients had minimal drop in the peripheral blood CD34 counts post bortezomib. Median number of CD34 cells collected in15 patients (part B) were 5.06 x 106 CD34 cells/kg (range 4-15.1). 18 patients proceeded to ASCT and median time to neutrophil engraftment (ANC ≥500/cumm) post transplant was 12 days (range 11-16) and platelet engraftment (Plt count ≥ 20,000/cumm) was 18 days (range 15-27). There was no significant change in DC1/DC2 ratio in both groups following treatment with bortezomib and G-CSF (Figure 1). In group A all three patients collected goal CD34 count on day 5 and 2/3 patients collected 〉4 x106 CD34 cells/kg on D6 post bortezomib and1/3 patients collected 2.6 x 106 on D6 post bortezomib. In group B (n=17), 2 patients were unable to collect because of low CD34 counts on D4 and D5, 11 pts collected the goal in one day (D 5) and 4 pts required two days of apheresis (D 5 and 6). None of the patients received D7 bortezomib. Conclusion: Use of bortezomib during autologous stem cell collection was safe and well tolerated. Majority of patients had increase in peripheral blood CD34 counts post bortezomib administration on D4. Future trials should explore bortezomib as an alternate strategy to chemo-mobilization in combination with growth factors. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 2. Figure 2. Disclosures Off Label Use: Bortezomib for stem cell mobilization. Lum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding. Abidi:celgene: Speakers Bureau; Millenium: Research Funding.

Description: Second autologous stem cell transplant (ASCT) is a treatment option for multiple myeloma (MM) patients (pts) who have disease progression after first ASCT. About 20% of MM pts have evidence of renal dysfunction and many more develop it subsequently. Outcomes of second ASCT in pts with renal dysfunction have not been described. We identified 18 pts at our institution who underwent a second ASCT for relapsed MM and had evidence of renal dysfunction (creatinine clearance ≤ 60ml/min/1.73m2). Pts who underwent a planned tandem transplant were excluded from this analysis. Patient characteristics are shown in Table 1. The median age of pts was 61 years (range, 49-72). The median time between first and second ASCT was 49.8 months (range, 19.2-81.9). Ten pts received one chemotherapy regimen while nine pts received two or more chemotherapy regimens between first and second ASCT. The chemotherapy regimens used between first and second transplant included IMid based (n=6), proteosome inhibitor based (n=3) and combination of both (n=9). Approximately half of the pts had progressive disease at the time of second ASCT. Median creatinine clearance at the time of second ASCT was 43.5 ml/min//1.73m2. All pts received G-CSF 5µg/Kg from day + 6 till absolute neutrophil count was ≥1500/µL, norfloxacin, acyclovir and fluconazole were used for antimicrobial prophylaxis during the hospitalization. One pt was dialysis dependent. Patients received a median dose of melphalan of 140mg/m2 (range 100-200 mg/m2). Median follow up post second ASCT was 17.1 months (range, 2.4- 100). One pt died 74 days after the transplant due to multi- organ failure. Disease status at day 100 post ASCT is shown in Table 2. Thirteen of 17 pts had a partial response or better after second ASCT. Of 17 evaluable pts at day 100, twelve had an upgrade from the disease response category achieved with the last regimen used prior to second ASCT while five pts had stable disease response. Three pts received maintenance therapy after the second ASCT with bortezomib(n=2) and lenalidomide (n=1). Figures 1 and 2 show the overall survival (OS) and relapse free survival (RFS). Median RFS was 22.2 months and median OS was 27 months. The outcomes of patients with renal dysfunction who underwent ASCT in the era of novel agents at our institution are comparable to those reported for second ASCT. The transplant related mortality was not higher than expected and the median PFS of about 2 years makes the option of second ASCT in this group of patients a valuable treatment modality. The utility of maintenance therapy after the second ASCT is not established, but may have contributed to the durable responses seen in some pts assessed herein and deserves to be investigated further. Table 1: Pt Characteristics (N=18) Patient Characteristics N (%) Median Age (range) 61 years(49-72) Median Time from First ASCT (range) 49.8 months(19.2-81.9) Gender Male 9(50%) Females 9 (50%) Race Caucasians 13 (72%) Others 5 (28%) Disease status at time of ASCT PD 9 (50%) SD 5 (28%) PR 1 (5.5 %) VGPR 2 (11%) CR 1 (5.5%) Median creatinine clearance (range) 43.5 (5-59) Subtype IgG Kappa 10 (56%) IgG Lambda 6 (33%) Kappa Light Chain 2 (11%) Cytogenetic Risk Standard 10 (56%) High Risk 4(22%) Unknown 4 (22%) Melphalan Dose median mg/m2( range) 140 (100-200) {100(2pts), 140(10pts), 180(1pt), 200(4pts)} Median CD 34 Cell dose x106/kg (range) 4.66(2.6-27.5) Median Engraftment Day (range) WBC 11 (9-16) Platelets 21 (12-61) Median Days of Hospitalization (range) 19(11-74) PD: Progressive disease, SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: complete response; WBC White blood cells Table 2 Disease status at Day 100 post ASCT Disease status at Day 100 post ASCT N(%) CR 4 (22%) VGPR 4 (22%) PR 5 (28%) SD 3 (17%) PD 1 (5.5%) NOT AVAILABLE * 1 (5.5%) PD: Progressive disease, SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: complete response; *Pt died at day 74 post second ASCT PD: Progressive disease, SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: complete response; * Pt died at day 74 post second ASCT Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.