ALBERT

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: 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: AGVHD is a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Primary treatment of aGVHD with corticosteroids achieves a complete response (CR) rate of 20–40%. Mesenchymal stem cells (MSC) derived from adult bone marrow have immunomodulatory effects. Preclinical and clinical data suggest that MSC inhibit T-cell alloreactivity. Thus, we initiated a trial to investigate the use of Prochymal, ex-vivo cultured adult human MSC derived from unrelated donors, added to conventional steroid therapy for the primary treatment of aGVHD. Patients (pts) and Methods: Pts must have had newly clinically diagnosed aGVHD, grades II-IV using standard grading criteria, after undergoing a related or unrelated allogeneic SCT, or donor lymphocyte infusion (DLI). Endpoints of the study included safety of administration of Prochymal and response rates of aGVHD by day 28 after Prochymal infusion. Treatment with steroids (2mg/kg) and Prochymal, randomized to 2 (low) or 8 million (high) cells/kg, was initiated at the time of GVHD diagnosis. Pts were kept at therapeutic levels of tacrolimus, cyclosporine, or MMF for GVHD prophylaxis. 2 doses of Prochymal were given 3–5 days apart, with the first given within 72 hrs of steroid initiation. Corticosteroids were maintained at 2 mg/kg for at least 1 week. Pts were monitored for response and toxicity weekly for 4 weeks, and then followed for safety on a 2 year long-term follow-up study. Results: 32 pts were enrolled with interim data available for 30 pts (21 males, 9 females) with median age 52 (range 34–67). AGVHD developed following matched sibling (n=15), matched unrelated (n=11), or DLI (n=4) infusions. Overall aGVHD was noted to be grade II (n=20), grade III (n=7), and grade IV (n=3), and involved GI (n=13), skin (n=11), GI and skin (n=4), and GI and liver (n=2). Prochymal dose was low in 17 pts and high in 13 pts. All pts received both Prochymal infusions. 26 of 29 evaluable pts (90%) initially responded to treatment of their aGVHD: 19 achieved CR with no evidence for GVHD, and 7 achieved PR as documented by a reduction in 1 organ stage. Nine pts (31%) eventually required a second line agent to control aGVHD. No infusional toxicities were noted. One pt developed atrial fibrillation 1 day following the second Prochymal infusion. No unexpected ectopic tissue formation was noted in any pt by CT scans at day 28. Currently, 8 pts have died from progression of aGVHD (n=2), intracranial bleed following fall (n=1), relapse (n=1), and infection (n=4) at a median of 44 days (range 13–58) following Prochymal infusion. Conclusions: The addition of Prochymal to corticosteroids resulted in a high response rate with minimal added toxicity when used for the primary treatment of aGVHD, and suggests that MSC have unique biological properties that may be effective for treatment of GVHD. Longer follow-up is necessary to determine if Prochymal has any impact on survival. Phase III studies are warranted, including studies in steroid refractory GVHD.

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.

Description: Introduction Chronic graft-versus-host disease (cGVHD) is a major factor determining long term outcome and quality of life following allogeneic hematopoietic cell transplantation (AHSCT). In fact, cGVHD is the leading cause of late non-relapse mortality (NRM) and morbidity after AHSCT. The rates of severe cGVHD using NIH consensus criteria reported in the literature are 15-38%. Effective regimens are needed to reduce the severity of cGVHD and improve NRM. We analyzed and updated the long term outcomes of our phase 2 trial evaluating the efficacy of intermediate dose rabbit anti-thymocyte globulin (Thymo) in combination with tacrolimus and sirolimus for the prevention of acute and chronic GVHD after unrelated donor transplantation. Methods In a Phase II trial, 47 adult patients (pts) underwent AHSCT from unrelated donors using Thymo, tacrolimus, and sirolimus for GVHD prophylaxis. Thymo was given as follows: 0.5 mg/kg day -3, 1.5mg/kg day -2, and 2.5mg/kg day -1. Chronic GVHD was measured using NIH consensus criteria. Results Twenty-two pts received 8/8 and 25 received 7/8 HLA matched unrelated grafts. Thirteen pts received a reduced intensity preparative regimen, while 34 pts received a full intensity regimen. The median follow-up duration was 45.2 months (95% CI 37.7-48.8), with minimum follow up of 30 months. At 4 years of follow up, the cumulative incidence of NIH severe cGVHD a, was 6.4 % (95% CI 1.6-15.9), and overall cumulative incidence of cGVHD was 48.9% (95% CI 33.6-62.6). Of 20 pts who are alive and disease free, only 4 pts continue to need systemic immune suppression at the last follow up. At 4 years of follow-up, the cumulative incidence of NRM and disease relapse were 27.7% (95% CI 15.7- 41.0) and 30.0% (95% CI 17.5- 43.6), respectively. There has been one non relapse death beyond 12 months and none after 18 months of follow up. Only one pt died from cGVHD and bronchiolitis obliterans, while two other pts had minimal symptoms from bronchiolitis obliterans. Progression free survival (PFS) and overall survival (OS) at 2 years were 50% (95% CI 35-64) and 56% (95% CI 42-70). Median OS is 33.9 months [95% CI (9.8 -*) *the upper limit of the CI was not calculated due to the pattern of censoring] All patients were censored after 40 months, so PFS and OS could not be calculated at 48 months. The median karnofsky performance status at 2 years was 90%. Conclusion At long term follow up, the combination of Thymoglobulin, Tacrolimus, and Sirolimus was associated with low incidence of severe cGVHD, low incidence of late NRM, and good performance status. Further validation of these results in randomized phase III trials is needed. Disclosures: Al-Kadhimi: Genzyme: Research Funding. Off Label Use: The use of Thymoglobulin® for GVHD prevention.

Description: Introduction: Patients with AML and MDS who are age 60 or above represent a discrete group of patients with a different disease biology compared to younger patients. These patients are often not offered allogeneic hematopoietic stem cell transplant (HSCT) as a curative intent because of concern of increased nonrelapse mortality (NRM) and poor overall survival (OS). Hence, the information on transplant outcomes among this population is very limited. Recently with the use of better supportive care measures and reduced intensity preparative regimens, patients greater than 60 are often recommended to proceed to transplant. This study evaluates our single center experience of allogeneic transplantation in patients with MDS and AML aged 60 and older. Patients and Methods: We retrospectively evaluated 60 years or older consecutive patients with AML and MDS who underwent allogeneic HSCT between January 2005 and December 2014. The primary objectives of our study were to determine NRM, relapse, relapse free survival (RFS) and OS at 1 year following transplant. The secondary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) at 1 year, length of stay and readmission rate in the first 100 days following transplant. Results: Between January 2005 and December 2014, 159 patients underwent allogeneic HSCT with the median age of 64 (range, 60-75) years and median follow-up duration for OS of 3.34 (95% CI, 2.51-3.87) years. Increasing number of patients were transplanted in recent years, i.e., 67% patients between 2010-2014 compared to 33% between 2005-2009. One hundred three patients (65%) had AML and 56 patients (35%) had MDS. Forty-nine patients (31%) received full intensity regimen and 110 patients (69%) received reduced intensity regimen. Fifty-two patients (33%) underwent allogeneic related transplant and 107 patients (67%) had allogeneic unrelated transplant. Thymoglobulin based GVHD prophylaxis was given in 77 patients (48%) whereas non-thymoglobulin based GVHD prophylaxis was given in 82 patients (52%). The median day to neutrophil and platelet engraftment was 11 (range, 7-22) days and 16 (range, 0-675) days, respectively. Graft failure occurred in 3 patients. At 1-year follow-up, the cumulative incidence of grade II-IV aGVHD was 39.7% (95% CI, 32.0-47.2%), grade III-IV aGVHD was 20.8% (95% CI, 14.9-27.5%) and cGVHD was 54.1% (95% CI, 46.0-61.5%). The cumulative incidence of chronic extensive GVHD was 39.8% (95% CI, 32.1-47.4%). Blood stream infection, cytomegalovirus reactivation, Epstein-Barr virus reactivation, C. difficile diarrhea occurred in 44%, 35%, 22% and 26% of patients, respectively. At 1-year follow-up, NRM was 25.3% (95% CI, 18.8-32.3%), RFS was 53.3% (95% CI, 46.1-61.7%), relapse rate was 21.4% (95% CI, 15.4-28.1%) and OS was 56.4% (95% CI, 49.2-54.7%). The median day of hospitalization following transplant was 26 (range, 19-112) days and almost half (52%) of patients were readmitted in the first 100 days following transplant. Leukemia recurrence was the most common cause of death. Multivariable analysis demonstrated high disease risk index to be the independent predictor of poor RFS, OS and higher relapse rate (p

Description: Introduction: Peri-transplant radiation (XRT) in Hodgkin Lymphoma (HL) patients undergoing autologous stem cell transplant (ASCT) has been associated with improved local control. However, this has not been well established with increased use of novel agents in peri-transplant setting. Methods: This was a retrospective analysis of HL patients who underwent their first ASCT between 2000 and 2018 at Karmanos Cancer Institute in Detroit, Michigan. Peri-transplant radiation was defined as XRT within 3-month window of autologous transplant. Novel agents included brentuximab, check-point inhibitors (CIs), and other targeted agents. The primary endpoint was to compare overall survival (OS) based on utilization of peri-transplant XRT and novel agents with standard salvage chemotherapy. Secondary endpoint was to assess the OS benefit of novel agent use in the post-transplant setting. Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between OS and nine prior chosen predictors (bulky relapse, pulmonary or bone marrow relapse, extranodal disease, CT/PET response [CR vs less than CR], novel salvage [anytime], peri-transplant XRT, site of relapse [local vs systemic], maintenance brentuximab, relapse after initial diagnosis [〉1 year vs ≤1 year]). Results: From 2000-2018, there were total of 220 patients who underwent ASCT for HL. Patients underwent ASCT median of 575 days after initial diagnosis. 65 (30%) patients had XRT during initial treatment and XRT was utilized less frequently in all patients (13% vs 35%) and stage I-II patients (29% vs 46%) who were diagnosed after 2010. Peri-transplant XRT was used in 30 (14%) patients and was utilized similarly in patients who had ASCT before or after 2010 (13% vs 14%) (Figure 1). There was no difference in baseline characteristics (bulky relapse, local vs systemic relapse, etc.) of patients who did or did not receive peri-transplant XRT (Table 1). Novel salvage was used in 32 (15%) patients at any time before transplant (Figure 1). Median OS of all the patients who had ASCT was 11 years [7.6-NR] and PFS was 4.3 years [2.3-7.4]. Median OS of patients who had peri-transplant XRT was not reached [9.4-NR] compared to 7.7 [5.3-NR] years for those without peri-transplant XRT [HR 0.38; 95% CI 0.15-0.96; p=0.033] (Figure 2); on the contrary, there was no difference in PFS between the two groups. Median OS of patients who had novel salvage at any time was not reached [4.3-NR] compared to 11 [7.6-NR] years for those without novel salvage [HR 1.08; 95% CI 0.43-2.72; p=0.877]. Median OS of patients who had either novel salvage (anytime) or peri-transplant XRT was not reached [9.4-NR] compared to 11 years [6.5-NR] for those who had chemotherapy salvage only [HR 0.64; 95% CI 0.32-1.26; p=0.193]. In the multivariable analysis, less than CR to salvage therapy and lack of peri-transplant XRT use were associated with worse OS. There were total of 85 (39%) patients who progressed after ASCT. Median OS for those patients was 3.5 years [2.3-8.8] and PFS was 1 year [0.8-1.5] after relapse from ASCT. The median OS for patients who received novel agents (brentuximab 61%, CI 14%) during first progression after ASCT was 6.9 years [2.3-NR] after relapse from ASCT compared to 2.9 years [2.3-NR] for those that did not [HR 1.47; 95% CI 0.72-3; p=. 288]. In addition, the median OS for patients who received novel agent at any time after transplant was 6.9 years [2.6-NR] after relapse from ASCT compared to 2.5 years [2.2-7] for those who did not [HR 1.96; 95% CI 1-3.86; p=0.048] (Figure 3). Lastly, OS after relapse from ASCT was better if patients progressing on novel agent post-transplant received another novel agent for their successive therapy rather than any other treatment [HR 4.87; 95% CI 1.14-20.8; p=0.018]. Conclusions: We show that there was a lack of standardized patient selection for utilization of peri-transplant XRT and its use was similar before and after the novel agent era. Peri-transplant XRT was possibly used in patients who had residual disease or other high -risk features that could not be identified due to retrospective nature of this study and, despite this, use of peri-transplant XRT was associated with modest survival benefit. Surprisingly, use of novel agent at any time during salvage was not associated with survival benefit. Utilization of novel agents at any time after post-transplant progression was associated with OS benefit. Disclosures Deol: Kite: Other: Advisory board; Novartis: Other: Advisory board; Agios: Other: Advisory board.

Description: Background: Autologous hematopoietic stem cell transplantation (AHSCT) is an important modality in the management of many hematologic malignancies. The first step for patients who are candidates for AHSCT is adequate stem cell collection. Recombinant granulocyte-colony stimulating factor (GCSF) is used for stem cell mobilization. Plerixafor has been used to increase the yield of mobilized stem cells, either upfront or pre-emptively when pre-apheresis peripheral blood CD34+ cell count is low. In the last few years, biosimilar G-CSF (Zarxio®) has become available. Although biosimilar G-CSF may reduce mobilization costs when used alone, the effect on use of additional mobilization agents like plerixafor has not been well studied. Therefore, we investigated whether there was a difference in the rate of Plerixafor usage among patients who were mobilized using biosimilar G-CSF (Zarxio®) compared to the original G-CSF (Neupogen®). Methods: This was a retrospective single institution study. We utilized the Karmanos Cancer Insitute's blood and marrow transplantation database to collect data on patients who underwent stem cell mobilization for AHSCT using either Neupogen® (N) or Zarxio® (Z), between January 2015 and June 2017. Per institutional policy, patients received G-CSF 10µg/Kg for 5 days and received Plerixafor if peripheral CD34+ cell count on the first planned day of collection was 〈 20/uL. The target CD34+ stem cell dose for AHSCT was 2 x 106/kg. Kruskal-Wallis tests were used to compare two groups for continuous variables and Chi-squared or Fisher's exact tests for categorical variables. Logistic regression models were used to assess associations between six pre-specified predictors (mobilization, age, radiation therapy, median WBC/ platelet count prior to initiation of mobilization and disease status at time of mobilization) and transplant status. Results: A total of 370 patients underwent stem cell mobilization during the study period. N was used for mobilization in 197 patients while Z was used in 173 patients. Patient characteristics are shown in Table 1. Median age was 61 years (18-78). There were no significant differences in the baseline patient characteristics other than slightly lower median WBC count prior to mobilization, in patients who received N for mobilization. The indication for stem cell mobilization was Multiple myeloma (67%), Non-Hodgkin's lymphoma (21%), Hodgkin Lymphoma (8%) and Amyloidosis (4%). There was no statistically significant difference in plerixafor utilization between the two groups (45% in N group vs 43% in Z group (p-value: 0.794). There was also no difference between the groups in the peripheral CD34+ cell count on firts planned day of collection, number of collected stem cells, total days of apheresis, need for a second mobilization, rate of transplant and duration of transplant hospitalization (Table 2). In MVA, older age and platelet count 〈 100 were the only 2 factors which adversely impacted the possibility for a patient to proceed to transplant (Table 3). Conclusion: There was no difference in plerixafor utilization among the two groups. Previously recognized risk factors like older age and low platelet count were identified as risk factors for not being able to undergo an AHSCT. The cost of biosimilar is about 50% less than the original G-CSF and based on our analysis of a large number of patients at a single institution, biosimilar G-CSF provides significant cost savings for stem cell mobilization. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

Description: Women with stage IV metastatic breast cancer (mBrCa) have limited treatment options since toxicities from chemotherapy and radiotherapy become limiting. Non-toxic immunotherapy approaches to improve targeting and cytotoxicity directed at breast cancer are needed. Our earlier study showed that anti-CD3 activated T cells (ATC) could be expanded in culture and then armed with anti-CD3 × anti-Her2/neu bispecific antibody (HER2Bi). The armed ATC mediate enhanced specific cytotoxicity, proliferate, and induce cytokine/chemokine secretion (J Hematotherapy & Stem Cell Res10:247, 2001). In a Phase I trial using ATC armed with Her2Bi, 18 Stage IV BrCa patients (pts) were treated with 8 infusions (twice/week) for 4 weeks totaling 40 (6 pts), 80 (2 pts), 160 (7 pts), and 320(1 pt) billion ATC armed with Her2Bi without dose-limiting toxicities. The most frequent side-effects were chills, fever, and hypotension that were easily controlled with medications. Two stage IV mBrCa patients had minor responses with decreases in CEA (35.2 to 4.1 ng/ml) or CA 27-29 (57.7 to 35.6 U/ml) and one pt had partial response with a decreased liver metastatic lesion. None of the pts developed human anti-mouse antibodies levels above10 ng/ml. Immunoaffinity-depletion of BiAb-armed ATC from PBMC of a high risk IV mBrCa pt at post-treatment time points showed an increase in anti-BrCa tumor cell activity exhibited by endogenous immune cells that persisted up to 4 months after treatment. Increasing proportions and absolute numbers of CD25+ cells in CD4+ and CD8+ subsets were observed as a function of treatment with nearly all CD4+ and CD8+ cells being CD25+ by 1 week post-final infusion. Significant treatment-associated elevations (several log increases over baseline) of circulating IFNγ, TNFα, IL-2, IL-5, IL-10, IL-12p70, and IL-13 were detected in serum of nearly all of the patients beginning 1–2 weeks after initiation of infusions. Particularly remarkable was the 3 log increase of mean (n=9) serum IL-12p70 from 0 to 1200 pg/ml. There was a Th1 shift that persisted during therapy. To date, results from the phase I clinical trial suggest that Her2Bi-armed ATC activate the endogeneous immune system to generate an adaptive immune responses despite the presence of high tumor burdens. The figure shows the overall survival for 18 women (All) treated on the phase I protocol with the median survival not yet defined for the HER2/neu 3+ group and the entire study group. The median survival for the 9 pts with Her2/neu negative disease was 21.5 months. Together these data are encouraging and strongly suggest infusions of armed targeted T cells may immunized the patient against their own tumor antigens leading to immunoreactivity manifested as the development of a persistent CTL response that may lead to improved overall survival. Figure Figure

Description: Abstract 2387 Background: Most Autologous stem cell transplant (ASCT) eligible Multiple Myeloma (MM) patients (pts) will have persistent disease after ASCT. Achieving a Complete Response (CR) after ASCT correlates with significantly longer progression free survival (PFS) and overall survival (OS). Since only 30–40% of the pts achieve a CR post ASCT there is a strong rationale for investigating post ASCT maintenance therapy with novel agents to improve PFS and OS. Maintenance therapy can have a potential role in achieving CR as well as maintaining CR post ASCT. The maintenance dose of novel agents including Bortezomib (B) was arbitrarily selected and has not been evaluated in Phase 1 trials. We designed this Phase 1 study to determine the most tolerated Maintenance dose (MtMD) of B after ASCT. To our knowledge, there are no phase 1 trials conducted to determine the maintenance dose of B post ASCT. Methods: We enrolled 15 pts from 11/28/2005 to 10/27/2009. Fourteen patients are evaluable. The primary objective was to determine the MtMD of B in 3x 3 dose de-escalation design. The secondary objectives were to evaluate CR, Overall Response (OR) and response duration. Two pts were enrolled in level (L) 1 utilizing therapeutic dose of B, 1.3 mg/m2on days (D) 1, 4,8 and 11 in a 21 day cycle. Both pts experienced dose limiting toxicities (DLT). Six pts were then enrolled in dose L 2 utilizing B, 1.3 mg2 on D 1, 4, 8 and 11 in a 28 day cycle. Seven pts were thereafter enrolled in dose L 3 utilizing B 1mg/m2 on D 1, 8 and 15 in a 28 day cycle. All pts who underwent ASCT (Day 0) were eligible and registered between D+30 to D+120 after ASCT. Conditioning regimen included melphalan at a median dose 200 mg/m2 (140-260). A maximum of 8 cycles of B were planned. B was administered at a median duration of 107 days (52-123) post ASCT. In order to properly assess dose dependent DLT, pts who received 〈 4 cycles for reasons other than B -related toxicity were replaced. Enrollment was moved to the next lower dose level if ≥2 DLTs were observed. The pts characteristics included a median age of 58 years old (38-68), median KPS of 90% (70-100) and 2 pts with baseline grade 1 neuropathy. The baseline disease status at the time of ASCT included 4 pts in CRu, 3 pts in VGPR, 4 pts in SD, 3 pts in PR and 1 pt with relapsed disease. Five pts had high risk features on bone marrow FISH analysis. Nine pts had received induction with immunomodulatory agents and 6 pts were treated with B based induction regimens. Results: Two pts developed DLT on L 1. One patient experienced Grade 2 neuropathy that did not resolve in two weeks and required B dose reduction. The other patient experience Grade 3 neutropenia requiring filgrastim support. In addition, 2 pts on L2 developed DLT. First pt had multiple hospital admissions due to high grade fever and dehydration. Second patient experienced Grade 2 neuropathy that did not resolve with treatment interruption and therefore B was discontinued after two cycles. No DLTs were observed in L3. Eight cycles of B were administered in L1. In L 2, 3pts received 8 cycles (1 off study), 1 pt received 3 cycles and 2 pts received 2 cycles of B. In L3, 6 of 7 pts received 8 cycles. After 1 year of post ASCT, 1 pt was in CRu, 1 pt in PR,3 pts were in SD, 2 pts had PD, 3 pts with relapsed disease and 5 pts were off-study (2 experienced DLTs, 2 withdrew consent and 1 failed to receive at least 4 cycles). All pts except 1 are alive as of 8/2/2010. The median duration of follow up for the entire cohort is 24 months (11-53).The median duration of response in L3 was 12 months (11-24). One pt enrolled on L3 died of sepsis during the course of follow up. He did not complete at least 4 cycles of B and therefore was not evaluable. Conclusion: To our knowledge, this is the first study that determines MtMD of B post ASCT. We conclude that B at a dose of 1 mg/m2 on D 1,8 and 15 in a 28 day cycle can be safely given beginning 52 d post ASCT for maintenance. A maximum of 8 cycles were administered. Phase 2 studies will determine efficacy of this regimen utilizing dose L3. IMID= Immunomodulatory drugs, VAD=Vincristine, Adriamycin, Dexamethasone, RE=Relapse, CY= Cycles. 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.