Post Autologous Stem Cell Transplantation Research Articles

Ibrutinib, Bendamustine, Rituximab Combination for Relapsed and Refractory Aggressive B Cell Lymphoma — Interim Analysis of Phase II Clinical Trial

Background: Ibrutinib is an orally-administered inhibitor of Bruton's tyrosine kinase. It is an effective agent in diffuse large B cell lymphoma (DLBCL), specifically of the Activated (ABC) type (Younes A et al, Lancet Oncol 2014). The combination of ibrutinib, bendamustine, and rituximab (IBR) was reported to be potent for B cell lymphomas, including DLBCL, in a phase I clinical trial (Maddocks et al, Blood 2015). We aimed to explore the efficacy of the IBR regimen in patients with relapsed & refractory (RR) aggressive B cell lymphoma (ABCL), who were either transplant ineligible or in relapse post autologous stem cell transplantation (ASCT). We report here, the interim analysis of a phase II clinical trial.Methods: Patients with RR ABCL of all subtypes as well as transformed low-grade lymphoma and grade 3B follicular lymphoma were eligible. Patients with CNS lymphoma, inadequate bone marrow function or previous exposure to bendamustine or ibrutinib were excluded. All diagnostic biopsies were centrally reviewed or repeated. PET scans were interpreted according to the Lugano criteria 2014. Rituximab and bendamustine were given for a six 28 days cycles in their standard dose (rituximab 375 mg/m2 in day 1 and bendamustine 90/70 mg/m2 day 1 and 2). Ibrutinib 560 mg orally, was administered continuously from day 1. PET scans were repeated after 3 and 6 cycles of therapy and then every 16 weeks up to 3 years. Patients that achieved a response after 3 cycles and who were eligible, could undergo either allogeneic or autologous stem cell transplantation. For the interim analysis, 34 patients were screened, and 32 of them were treated.Results: Seventeen male (53%) and 15 (47%) female patients, median age 69 (28-94) were treated. All patients received at least one prior line of rituximab-containing therapy mostly RCHOP (n=28, 87%). Ten (31%) participants received the IBR therapy as a second line and 22 (69%) as a third-line regimen, 6 (19%) received prior ASCT. Eight (25%) patients had relapsed disease, and 24 (75%) were refractory. Twenty-nine patients had denovo aggressive B cell lymphoma, including 12 (37%) ABC-DLBCL, 5 (16%) GCB-DLBCL, 6 (19%) undefined DLBCL, 2 (6%) primary mediastinal lymphoma and 4 (12%) double hit high grade lymphoma. Two patients had transformed low grade and 1 grade 3B follicular lymphoma.We recorded 258 adverse events (AEs); 11 (4%) were Serious Adverse Events (SAEs) and 3 (1%) adverse events were of particular interest. SAEs that were related to ibrutinib were documented in 4 patients one time each (1.6%) and included atrial flutter/fibrillation, fatigue, and thrombopenia.Of the 32 patients 27 were evaluable for response, the additional 5 patients had early clinical progression. Complete response (CR) was documented in 8 (30%), partial response in 4 (15%) and stable disease in 2 (7%) translating to overall response rate (ORR) of 45%. On an intention to treat analysis ORR was 38%. There were no statistically significant differences in response rates between relapsed vs. refractory patients as well as ABC type vs. others.Four patients were referred to transplant after achieving CR or PR, 2 to ASCT and 2 to allogeneic stem cell transplantation. With a median follow-up of 14 months, all 4 patients remained alive and in remission. Median PFS and OS for the entire cohort (n=32) was 2.7 and 7.1 months, respectively. Both PFS and OS were significantly better for patients who achieved CR. Median PFS for patients with no CR was 2.5 months and was significantly different from patients with CR (p=0.008, log-rank test, figure 1a). Median OS for patients without a CR was 5.9 months; no deaths occurred among patients who achieved CR (p=0.032, log-rank test, figure 1b).There were no significant differences in OS or PFS between relapsed and refractory patients as well as between the different histological subtypes.Conclusions: We demonstrated that the IBR regimen is both safe and effective for patients with RR ABCL. Our patient population was of advanced age and mostly refractory, and despite that, we were able to show 45% ORR. Four of the patients that were chemorefractory and therefore transplant ineligible were able to undergo transplants after achieving remissions with this regimen, all of them are alive and in remission. We conclude that this regimen has promising results as a salvage regimen for RR ABCL patients both as a sole therapy or as a bridge to transplant, and it should be investigated in further clinical trials. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study

The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study

Non-Effectiveness of Using RICE Post RDHAP or RDHAP Post RICE after Failure of First Line Salvage Therapy in DLBCL Patients Who Are Eligible for ASCT

Background: The treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) remains challenging. The use of salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in young and fit patients is considered the standard of care. RDHAP (rituximab, dexamethasone, high dose cytosine arabinoside and cisplatin) and RICE (rituximab, ifosfamide, carboplatin, and etoposide) are the two most commonly used salvage-regimens with comparable efficacy (CORAL study). However, nearly 40% of the patients do no respond to these regimens and subsequently they do not proceed to ASCT. There are no guidelines concerning the choice of a second-line salvage regimen. There are sparse data in the literature concerning the best choice if the first salvage regimen fails. The aim of our study was to investigate the potential role of a second salvage regimen, before intensification, by RICE or RDHAP in patients with DLBCL refractory to the first line salvage therapy by RDHAP or RICE, respectively.Methods: We retrospectively included all patients aged 18 years and above who had a relapsed or refractory DLBCL and who were eligible for an autologous stem cell transplant (ASCT) between the years 2008 and 2017. They should have had progressive or stable disease (PD/SD) following first-line salvage based on RICE (group 1) or RDHAP (group 2) and should have received a second-line salvage based on RDHAP or RICE, respectively. Patients who received carboplatin or oxaliplatin instead of cisplatin in the RDHAP protocol were also included. All cases were discussed at a tumor board and the revised International Working Group response criteria for Malignant lymphoma were used to assess the response to chemotherapy. Information were collected using electronic medical record. Ethics committee approval was not necessary.Results: 100 patients' medical files were reviewed, out of which 69 were excluded for the following reasons: 5 patients lacked necessary information; 13 patients were treated for a non-DLBCL; 30 patients could not receive second line salvage therapy because of deterioration of their performance status; 21 patients because they received a bridging therapy (other than RICE or RDHAP) before second line salvage therapy. The study included 31 patients with 19 (61.3%) males and 12 (38.7%) females. The median age was equal to 59 years (standard deviation 14). DLBCL was at the initial diagnosis in all but 6 patients in whom DLBCL developed after an indolent lymphoma (follicular lymphoma in 4 and marginal zone lymphoma in 2). 70% had germinal centre B-cell subtype, while 30% had activated B-cell subtype. 70% were refractory to the primary therapy (CR not attained on primary therapy or relapsed within 6 months) and 30% recurred after a CR lasting more than 6 months. All patients included in group 1 (n=5) have received cisplatin during the treatment with the RDHAP regimen. Among the 26 patients included in the second group, 19 (73.1%) have received cisplatin, 4 (15.4%) oxaliplatin, and 3 (11.5%) carboplatin in first line salvage. No patient in group 1 responded to RICE and eventually no patient proceeded to ASCT. In the second group, 2 patients (7.7%) deceased after the first cycle of RDHAP because of drug related toxicities (1 due to ifosfamide-induced encephalopathy and 1 due to septic choc following febrile neutropenia). Ten patients (38.5%) responded to RDHAP, in whom an ASCT was planned. However, 2 patients could not proceed to ASCT because of peripheral stem cell collection failure. After a median follow up of 8.7 months, the median progression free survival (PFS) of the 8 patients who proceeded to ASCT was 6.3 months (CI 95% 2.6-10.1). Only 1 patient had a tumor response lasting more than 30 months. No factor was found to be associated with PFS on cox regression analysis (which included age, sex, type of DLBCL, and refractory or recurrent status).Conclusion: There is little information regarding the effectiveness of a second-line salvage therapy in patients not responding to first line intensification. All except one patient either could not proceed to ASCT or had a limited response (less than 3 months) post ASCT. In addition, the toxicity was not negligible considering that 2 patients died because of drug related events. This study suggests that patients with DLBCL who failed to respond to first line salvage by RDHAP or RICE should be considered for investigational therapies rather than second line rescue. DisclosuresRibrag:pharmamar: Other: travel; MSD: Honoraria; BMS: Consultancy, Honoraria, Other: travel; Roche: Honoraria, Other: travel; Amgen: Research Funding; argenX: Research Funding; Servier: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; Incyte Corporation: Consultancy; Gilead: Consultancy, Honoraria; Infinity: Consultancy, Honoraria; epizyme: Consultancy, Honoraria.

Survival Analysis from the CALGB Study of Lenalidomide Maintenance Therapy in Newly Diagnosed Multiple Myeloma Post-Autologous Stem Cell Transplantation Adjusted for Crossover (Alliance 100104)

Survival Analysis from the CALGB Study of Lenalidomide Maintenance Therapy in Newly Diagnosed Multiple Myeloma Post-Autologous Stem Cell Transplantation Adjusted for Crossover (Alliance 100104)

Long-Term Safety and Efficacy of Autologous or Allogeneic Donor Stem Cell Transplantation in Patients with Behçet's Syndrome

Background. Behçet's disease (BD) or syndrome is a rare chronic multisystem inflammatory condition with most manifestations attributed to vasculitis, including ulceration, skin lesions, with joint and other organ involvement. The poorest prognosis is reported in a small subgroup of BD patients with vascular, neurological, ocular, and gastrointestinal (GI) manifestations. The main aims of treatment are to suppress inflammatory exacerbations and recurrences, to prevent irreversible organ damage.1 There are few trial data supporting treatment options because of disease rarity and clinical heterogeneity. There are no previous or current clinical trials of hematopoietic stem cell transplantation (SCT) for BD, with only a few individual reported cases.Objective. To assess the safety and efficacy of SCT with the research question: “what is the overall survival and progression free survival (PFS) of patients with BD post autologous SCT (autoSCT) and allogeneic SCT (alloSCT), including those with the primary indication of refractory disease”.Design. Systematic review of reported cases, with updated data for 4 patients treated at our centre in Liverpool, UK.Data sources: PubMed, PubMed Central, Web of Science, OvidSP, Cochrane central register of controlled trials (CENTRAL), clinicaltrials.gov, eudract.ema.europa.eu, controlled-trials.com, free Google search, relevant conference proceedings, hand searching of reference lists, and contact with authors as necessary. Search terms were “behcet” and “transplant”. The search was last updated on 31 July 2018.Eligibility criteria. Cases of BD treated with autoSCT or alloSCT with available information on survival and PFS.Data extraction. Two reviewers independently assessed articles for inclusion, extracted data to assess patients, interventions, comparisons, and outcomes.Primary outcome measures. PFS and overall survival.Results. 32 patients with BD were reported in 25 identified articles, from Europe (47%), Asia (47%), and North America (6%). Median age was 36 years (range 6-60 years old), with 53% females, and 75% had had poor prognosis BD manifestations including vascular, neurological, ocular, and GI. Median time from BD diagnosis to SCT was 48 months (range 3-132), with a median of 3 (range 0-8) prior lines of BD-directed immune therapy.1 The primary indication for SCT was refractory BD in 41% of patients, and 59% of SCTs were primarily for other hematology indications. AlloSCT accounted for 59% of BD patients, the rest being autoSCT. Overall survival was 97% (Fig 1), after a median follow up of 31 months (range 0.2-135 months), with no difference between SCT types (p=0.36). The only death was from infection and sepsis prior to engraftment post alloSCT. ORR was 93%, and PFS was 112 months (95% CI 94-130) (Fig 2), with no difference by SCT donor types (p=0.46).Refractory BD was the main indication for autoSCT in 85%, and myeloma accounting for the remainder. Reported autoSCT conditioning regimens included melphalan 140-200 mg/m2 (54%), carmustine/etoposide/cytarabine/melphalan (BEAM) (23%), and cyclophosphamide combinations (23%), with 46% incorporating additional anti-thymocyte globulin (ATG). OOR was 92%, with complete remission (CR) achieved in 62%, partial remission (PR) in 31%, and stable disease (SD) in 8%.Refractory BD was the main indication for 11% of alloSCTs, and 5% had relapsed post autoSCT. Other hematology primary indications accounted for 89% of alloSCTs, with 69% for MDS, 11% AML, and 11% aplastic anemia. Trisomy 8 was recorded in 59%. Myeloablative conditioning was reported in 58%, with 26% using total body irradiation (TBI). OOR was 94%, with CR accounting of 84%. Acute or chronic graft versus host disease (GvHD) requiring therapy was poorly reported and lower than expected at 32%, with grade III-IV acute GvHD of 11%.Conclusion. SCT in BD appears to be safe and effective, with no clear difference in long-term survival or PFS by SCT type. AutoSCT is a beneficial treatment option for refractory BD. AlloSCT is also advantageous in BD, with less data in the refractory BD or post autoSCT salvage settings. Given the lack of a clinical trial, we present the most comprehensive evidence available supporting the practice changing role of SCT as a treatment option in BD.References. 1. Hatemi G, et al. 2018 update of the EULAR recommendations for the management of Behçet's syndrome. Annals of the Rheumatic Diseases 2018;77:808-18. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Simple Model for Predicting Post-Autologous Stem Cell Transplantation Outcome in Patients with Relapsed/Primary Refractory Hodgkin Lymphoma

Introduction: Current Hodgkin lymphoma (HL) therapies result in 80-90% progression-free survival (PFS). However, about 10-20% of patients with advanced disease relapse. The standard treatment for primary progressive or relapsed disease is salvage chemotherapy. For patients responding to this treatment, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is recommended. In a recently published study, an addition of post-transplant therapy has improved PFS. However, as this approach is associated with additional toxicity and increased financial burden, precise identification of patients who could benefit from this strategy is crucial. Our study provides outcome data of an unselected group of HL patients and suggests a model identifying individuals at high risk of disease progression in whom post-ASCT therapy could be advantageous.Methods: This retrospective study included 92 HL patients with a median age of 31years (18-66) at diagnosis and 36 years (20-67) at time of transplant, who underwent ASCT at Rambam and continued follow-up until 08/01/2017.Results: At a median follow-up of 48 months (0-195) for patients with an uneventful course and 6 months (1-33) for those who progressed, the relapse rate was 41%. The Kaplan Meyer plot for event-free survival (EFS) is presented in Fig 1. In group 1, including patients with negative PET-2 during first-line therapy, who had stage I-III HL at relapse, that occurred at ≥3 months from the end of therapy (n=43), a 5-year EFS was 0.82. In group 2, including patients with the parameters similar to those in group 1, but in whom PET-2 had not been performed (n=16), a 5-year EFS was 0.71. In group 3, incorporating patients with stage I-III HL at relapse that occurred at <3 months from the end of therapy or those with positive PET-2 (n=15) a 5-year EFS was 0.52. Group 4, comprising patients with stage IV disease at relapse (n=18), had a 5-year EFS of 0. In a bivariate analysis, HL stage IV at relapse (HR 2.56, 95% CI 1.06-6.15; p=0.036), positive PET-2 during first-line therapy (HR 2.41, 95%CI 1.1-5; p<0.02) and PET positivity post-salvage therapy (HR 2.39, 95%CI 1.24- 4.6; p=0.009) were associated with increased risk of disease progression after ASCT. The factors associated with improved prognosis were: age ≥40 years at transplant (HR 0.27, 95% CI 0.11-0.66; p=0.004) and relapse at ≥6 months from the end of therapy (HR 0.31 95% CI 0.11-0.92; p=0.035). In multivariate analysis, disease progression was associated with HL stage IV at relapse (HR 11.8, 95% CI of 4-34; p=0.000), PET-2 positivity or HL progression at <3 months from the end of therapy (HR 3.5, 95%CI 1.3-9.7; p=0.015).Conclusions: The current study suggests a 3-risk-factor model for prediction of post-ASCT HL progression, including stage IV disease at relapse, PET-2 positivity at first-line treatment or HL progression at <3 months from the end of therapy. Upon verification of our findings in an independent cohort, the suggested model could be employed in decision making regarding preemptive post-ASCT use of new therapeutic approaches, including biological and checkpoint inhibitor therapies, in HL patients who are at an increased relapse risk. [Display omitted] DisclosuresZuckerman:Cellect Biotherapeutics Ltd: Consultancy.

Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial

Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial

Infusion of NKp30/KIR2DL2 Natural Killer Cell Ratio and Survival Post-Autologous Stem Cell Transplantation in Lymphomas

Introduction: Our group (Porrata et al, BBMT 2016; 22: 1017-1023) previously published that the infusion of autograft natural killer (NK) cells correlates with survival post-autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) patients. A limitation of our previous study was the lack of killer-immunoglobulin-like receptor (KIR) analysis. Thus, we set up to investigate if the infusion of autograft activating and inhibitory KIR affects survival in NHL.Methods: From December 2007 to October 2010, 122 NHL patients participated in our Phase III clinical trial. A total of 111 patients finished the trail and samples were available for analysis. We analyzed the content of the autograft for inhibitory and activating KIR using flow cytometry analysis of each apheresis collection. Overall survival (OS) and progression-free survival (PFS) were analyzed from the date of transplant.Results: With a median follow-up of 82.8 months (range: 2.1-122.3 months), patients infused with an activating NKp30 (CD158b-CD337+) KIR ≥ 0.09 x 109 cells/kg experienced superior OS and PFS vs < 0.09 x 109 cells/kg: [OS: median was not reached vs 39.8 months, 5 years OS rates of 95% (95%CI, 56%-98%) vs 43% (95%CI, 22%-48%), p < 0.0001, respectively; and PFS: median was not reached vs 12.7 months, 5-years PFS rates of 77% (95%CI, 65%-86%) vs 13% (95%CI, 6%-24%), p < 0.0001, respectively]. Patients infused with the inhibitory KIR2DL2 (CD158b+CD337-) KIR < 0.066 x 109 cells/kg experienced superior OS and PFS vs ≥ 0.066 x 109 cells/kg : [OS: median was not reached vs 48.2 months, 5 years OS rates of 86% (95%CI, 75%-93%) vs 44% (95%CI, 31%-88%), p < 0.0001, respectively; and PFS: median was not reached vs 25.6 months, 5-years PFS rates of 62% (95%CI, 49%-74%) vs 31% (95%CI, 20%-44%), p < 0.0002, respectively]. We combined NKp30 and KIR2DL2 into NKp30/KIR2DL2 ratio. Patients infused with an NKp30/KIR2DL2 ratio ≥ 1.8 experienced superior OS (Figure 1) and PFS (Figure 2) vs < 1.8 : [OS: median was not reached vs 33.4 months, 5 years OS rates of 95% (95%CI, 86%-98%) vs 33% (95%CI, 21%-47%), p < 0.0001, respectively; and PFS: median was not reached vs 14.9 months, 5-years PFS rates of 76% (95%CI, 63%-85%) vs 14% (95%CI, 7%-27%), p < 0.0001, respectively]. Multivariate analysis revealed that the NKp30/KIR2DL2 ratio was an independent predictor for OS [HR = 0.03, 95%CI 0f 0.01-0.07, p < 0.0001] and PFS [HR = 0.17, 95%CI 0f 0.09-0.31, p < 0.0001].Conclusion: The NKp30/KIR2DL2 ratio provides a platform to develop an immunocompetent autograft to improve clinical outcomes in NHL patients undergoing ASCT. [Display omitted] DisclosuresAnsell:LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Celldex: Research Funding; Takeda: Research Funding; Merck & Co: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding.

Updated Results of a Phase II Study of Lenalidomide-Elotuzumab As Maintenance Therapy Post-Autologous Stem Cell Transplant (AuSCT) in Patients (Pts) with Multiple Myeloma (MM)

Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) after myeloablative AuSCT in pts with MM. Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAM F7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. The objective of this phase 2 trial is to evaluate the efficacy and safety of adding ELO to LEN as maintenance therapy post-myeloablative AuSCT. We report updated results of the primary (PFS) and secondary (overall survival [OS] and toxicity) endpoints. Patients and Methods: Between 4/15/2015-1/27/2016, 27 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2, q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=57 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until disease progression (PD). LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity > grade 1 and significant cytopenias (ANC The study9s primary endpoint is PFS, defined as time from AuSCT to PD or death (whichever occurs first), or time of last contact. Secondary objectives are best response, OS, incidence of second primary malignancies (SPMs) and adverse event (AE) profile. Total enrollment of 100 pts is planned. Patients are followed until death, withdrawal of consent or removal from study. Eligible pts received ≤2 lines of induction therapy, and are 60-210 days post-AuSCT. Results: Pts (n=84) have been treated for a median of 16 cycles (2-43). At study entry, 27 (32%) had complete response (CR), 36 (43%) had very good partial remission (VGPR), 20 (24%) had partial remission (PR) and 1 (2%) had minor remission (MR). Best response achieved to date on study is CR in 44 pts (52%), VGPR in 31 pts (37%) and PR in 9 pts (11%). For those who have converted to CR on study, median time to CR was 2 months. Of 22 pts in CR who have been tested for minimal residual disease (MRD) to date, 20 are negative by flow cytometry (minimum of 2 million cells evaluated). Three of 20 have converted from VGPR to MRD negativity while on study. With a median follow up of 23 months, 96% of pts (n=81) remain alive. Ten pts have had PD; of these, 6 had high risk cytogenetics. Two died of PD while receiving salvage therapy. One additional pt died on study in VGPR, after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Four pts withdrew for personal reasons, 4 were removed at physician discretion (prolonged cytopenias [1], drug rash [1], worsening memory impairment [1], therapy related myelodysplastic syndrome (t-MDS) [1]), and 2 lost insurance coverage. Estimated 3 year PFS is 81%. High risk cytogenetics adversely affected PFS (p=0.02). Grade 3-4 Hematologic AEs (no. of pts) were: neutropenia 32% (27), febrile neutropenia 15% (13), thrombocytopenia 8% (7), and anemia 7% (6). Grade 3-4 non-Hematologic AEs (no. of pts): respiratory infections 17% (15), diarrhea 14% (12), fatigue 13% (11), other infections 8% (7), peripheral neuropathy 7% (6), myalgias 6% (5), nausea/vomiting 4% (3), dizziness 2% (2), memory impairment 2% (2), maculopapular rash 2% (2), edema 1% (1). SPMs include intra-epidermal adenocarcinoma of the neck (1), mucinous appendiceal neoplasm (1), t-MDS (1), prostate cancer (1), and melanoma (1). Renal cell carcinoma was diagnosed in 1 pt, 15 months after removal from study for PD. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy during which 33% of 84 pts had improvement in quality of response while on therapy, including 20% who converted to CR. The number of pts experiencing improvement may be underestimated due to ELO interference with paraprotein measurement on electrophoretic studies. Additional follow up is required to determine if the improved quality of responses translate into improvements in PFS and OS. Available data supports conduct of a Phase 3 trial. Disclosures Thomas:Array Pharma: Research Funding; Amgen Inc: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding. Shah:Karyopharm Therapeutics: Employment. Lee:Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Patel:Abbvie: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Poseida Therapeutics, Inc.: Research Funding.

Lenalidomide As Maintenance Treatment for Patients with Newly Diagnosed Multiple Myeloma Post-Autologous Stem Cell Transplantation: A Pharmacoeconomic Assessment in the Netherlands

Background: Standard of care for patients with newly diagnosed multiple myeloma (NDMM) who are ≤ 70 years of age and who are fit is induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). However, this approach is not curative, and residual disease leads to disease relapse. Sustaining response and postponing relapse following ASCT is an important clinical goal, as early progression is associated with an increased risk of death.Lenalidomide (LEN) maintenance therapy has emerged as an important standard of care post-ASCT. Several clinical studies have shown that patients who received LEN maintenance therapy after ASCT had significantly longer progression-free survival (PFS) and overall survival (OS) in comparison with those who did not receive maintenance therapy. Other studies have indicated that active LEN maintenance treatment does not impair quality of life (Tay J, et al. Blood. 2017;130:abstract 2150). A recent EU5 cost-impact analysis suggested that LEN maintenance is potentially cost saving on direct medical costs by 24% over a 5-year period (Jackson G, et al. Blood. 2017;130:abstract 3405). To date, no study has specifically assessed the cost-effectiveness of LEN as maintenance treatment.Aims: To assess the cost-effectiveness of LEN treatment versus no maintenance treatment in transplant-eligible NDMM patients from a Dutch healthcare service perspective.Methods: A partitioned survival model structure was selected to provide a good fit to the supporting efficacy and safety data. The model was structured around 3 primary health states relevant to an NDMM patient's treatment trajectory: pre-progression state (encompassing on- and off-treatment periods), post-progression state (encompassing periods just prior to second-line treatment, on second-line treatment, and post-second-line treatment), and death.Efficacy and safety data were taken from a pooled meta-analysis of the CALGB 100104, GIMEMA RV-MM-PI-209, and IFM 2005-02 studies. Parametric models were used to estimate long-term survival.Utility data were applied from a real-world setting captured in the Connect® MM Disease Registry, which was used to calculate the progression-free (LEN), progression-free (no treatment), progressive disease (treatment-free), and progressive disease (second-line treatment) utilities. A 21 out of 28-day cycles dosing regimen for LEN was applied as recommended in the Dutch HOVON clinical guidelines. Costs (2016) and subsequent therapy data were derived from published literature and sources appropriate for the Dutch market. All drug costs are presented at list price. Healthcare resource utilization was informed from a EU5 (France, Germany, Italy, Spain, and the UK) real-world study (Ashcroft J, et al. Int J Hematol Oncol. 2018;Epub ahead of print).The total costs, life years gained (LYG) and quality-adjusted life years (QALYs) were estimated over a lifetime horizon. Multiple scenario and sensitivity analyses were conducted to test the robustness of the model results to key assumptions and data inputs.Results: The cost-effectiveness model predicted a QALY gain of 2.26 and a LYG of 2.79 for LEN in the base case analysis (Table). First-line drug costs of LEN contributed to an increase of EUR 147,707 in total costs versus no maintenance treatment. However, this was partially offset by savings of EUR 77,462 in subsequent treatment costs.LEN was shown to represent a cost-effective use of resources when compared with the Dutch willingness-to-pay (WTP) threshold for NDMM of EUR 50,000/QALY.Scenario analyses showed LEN remained cost-effective in settings representative of Dutch clinical practice. For instance, use of only the Dutch recommended dose (10 mg with dose reductions if needed) of LEN for NDMM gave an incremental cost-effectiveness ratio (ICER) of EUR 30,709. Scenario ICERs evaluating the key assumptions, aligning the subsequent therapy data as per in-trial use (EUR 49,059) and up to 83.9% of patients receiving 28 out of 28-day dosing, also remained below the WTP threshold.Conclusions: Introducing LEN as a maintenance therapy post-ASCT delays progression, improves survival, and reduces subsequent treatment-line costs. The use of LEN post-ASCT is cost-effective in comparison with no maintenance therapy in the Netherlands. [Display omitted] DisclosuresUyl-de Groot:Merck: Research Funding; Janssen- Cilag: Research Funding; Gilead: Research Funding; Genzyme: Research Funding; Celgene Corp.: Research Funding; Boehringer Ingelheim: Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Roche: Research Funding; Sanofi: Research Funding. Ramsden:Celgene Corp.: Consultancy; BresMed: Employment. Boersma:Celgene BV: Employment, Equity Ownership. Zweegman:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corp.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dhanasiri:Celgene International: Employment, Equity Ownership.

Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma.

The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively. In MM it seems that an approach based on combination treatment might be appropriate as unsatisfactory results have been yielded by monotherapy with PD-1/PD-L1 inhibitors. Immunomodulatory drugs, which are the current cornerstone of MM treatment, are the most logical partners as they possess many possibly synergistic effects. Nevertheless, the initially optimistic results have become disappointing due to the excessive and unpredictable toxicity of the combination of pembrolizumab with lenalidomide or pomalidomide. The FDA has suspended or put on hold several phase 3 trials in relapsed as well as in newly diagnosed myeloma patients. There are also other potentially synergistic and promising combinations, such as the anti-CD38 monoclonal antibody daratumumab, irradiation, etc. Not only the effective partner but also the correct timing of the initiation of the PD-1/PD-L1 inhibitors treatment seems to be of utmost importance. These strategies are currently being examined in various stages of myeloma such as during consolidation post autologous stem cell transplantation, targeting minimal residual disease or even in high risk smoldering myeloma.

Bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplant for multiple myeloma

We retrospectively reviewed all patients (n = 243) receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by autologous stem cell transplantation (ASCT) for multiple myeloma at the Mayo Clinic between January 2010 and April of 2017. Median age was 61 (interquartile range, 55–67) with 62% of patients being male. High-risk cytogenetic abnormalities (HRA) were present in 34% of patients. A total of 166 (68%) patients received some form of maintenance/other therapy post transplant (no maintenance (NM, n = 77), lenalidomide maintenance (LM, n = 108), bortezomib maintenance (BM, n = 39), and other therapy (OT, n = 19)). Overall response rate at day 100 post ASCT was 99% (CR 42%) with CR rate increasing to 62% at time of best response post transplant. Two year and 5 year overall survival rates were 90% and 67%, respectively, with an estimated median overall survival (OS) and progression-free survival (PFS) of 96 and 28 months, respectively. HRA was associated with a worse OS but not PFS (median OS: not reached for standard risk vs 60 months for HRA, P = 0.0006; median PFS: 27 months for standard risk vs 22 months for HRA, P = 0.70). The combination of VRd followed by ASCT is a highly effective regimen producing deep and durable responses in many patients.

Allogeneic stem cell transplantation following relapse post autologous stem cell transplantation in adult patients with acute myeloid leukemia: A retrospective analysis of 537 patients from the Acute Leukemia Working Party of the EBMT.

Patients with acute myeloid leukemia (AML) who relapse after autologous stem cell transplantation (ASCT) can be rescued by allogeneic SCT. We identified 537 adult patients with AML allografted in second complete remission (CR2) or first relapse after ASCT in the European Society for Blood and Marrow Transplantation (EBMT) registry. At 3 years post allograft, leukemia free survival (LFS) was 31.4% [95%CI 27.3-35.6], overall survival (OS) 39.5% [95%CI 35.1-43.9], relapse incidence (RI) 34.6% [95%CI 30.4-38.8], and nonrelapse mortality (NRM) 33.7% [95%CI 29.6-37.9]. RI was higher in patients transplanted in relapse in comparison to those transplanted in CR2 (HR 1.76, P = .004) and in patients who relapsed later after ASCT (HR 0.97 per month, P < 10-3 ), both translating into better LFS/ OS. Relapse was also lower in patients undergoing allogeneic stem cell transplantation (allo-HSCT) from an unrelated donor (UD) in comparison to those transplanted from a matched sibling donor (MSD) (HR 0.49, P < 10-3 ). NRM was increased in patients who received total body irradiation (TBI) pre-ASCT (HR 2.43; P < 10-4), translating into worse LFS/OS. LFS/OS did not differ between patients allotransplanted with reduced intensity (RIC) or myeloablative (MAC) conditioning. In conclusion, one third of adult patients with AML relapsing post ASCT can be rescued with allo-HSCT, with better LFS/OS in patients who relapsed later post ASCT, those transplanted in CR2 and those who had not received TBI pre-ASCT.

Plasma cell proliferative index post-transplant is a powerful predictor of prognosis in myeloma patients failing to achieve a complete response.

Myeloma patients failing to achieve a complete response post autologous stem cell transplantation are heterogeneous, some ultimately achieving deeper responses and prolonged remission, whilst others relapse rapidly with poor outcomes. We evaluated the prognostic impact of the plasma cell proliferative index (PCPI) post-therapy, in 382 patients with myeloma failing to achieve complete response at 100 days post-transplant. Sixty percent (n = 230) of patients had zero clonal or too few clonal plasma cells to accurately assess PCPI (No PCPI). The remaining 40% (n = 152) of patients had PCPI performed with 79% (n = 120) having a low PCPI and 21% (n = 32) having an elevated PCPI. Patients with an elevated PCPI had significantly shorter progression free and overall survival. The median PFS was 8 months for elevated PCPI vs. 19 months for low PCPI vs. 24 months for no PCPI (p < 0.0001). The median OS was 27 months for elevated PCPI vs. 79 months for low PCPI vs. not reached for no PCPI, p < 0.0001). On multivariable analysis post-therapy PCPI was an independent predictor of progression free and overall survival. The PCPI post-therapy is a powerful predictor of survival and risk stratifies myeloma patients failing to achieve complete response early in the disease course.

Abstract 2954: Immunomodulator maintenance post autologous stem cell transplant predicts better outcome in multiple myeloma patients with clonal hematopoiesis of indeterminate potential

Abstract Introduction: Multiple Myeloma (MM) is a clonal plasma cell malignancy, accounting for 10% of all hematological malignancies. Genetic analyses of large populations revealed that blood-specific somatic mutations in hematopoietic stem cells (HSCs) are commonly acquired during aging, a new entity labeled: clonal hematopoiesis of indeterminate potential (CHIP). We sought to determine the role of CHIP on survival of MM patients, specifically those receiving immunomodulators (IMiDs) maintenance (Lenalidomide or Thalidomide) post autologous stem cell transplant (ASCT). Methods: We tested cryopreserved HSCs of 629 MM patients who underwent ASCT between 2003 and 2011 at the Dana-Farber Cancer Institute. We used a target bait panel of 224 genes and performed deep-targeted sequencing at 978x coverage and ultra-low pass whole-genome sequencing at 0.1x to account for tumor contamination. Sequencing data was analyzed using ichorCNA, MuTect, and Strelka and mutation annotations were based on reported mutations in the literature and databases (ClinVar, COSMIC, cBioPortal, TCGA, and ExAC). Results: Our cohort had a median age of 58 years [24-83] at time of ASCT and median follow up post ASCT of 8 years [0.1-14.5]. 24% of patients had CHIP at time of ASCT, which is statistically similar to the 30% reported in non-Hodgkin's lymphoma (NHL), (Gibson et. al, JCO, 2017). The most commonly detected mutated genes were DNMT3A, TET2, TP53 and ASXL1. Acquiring mutations positively correlated with age (p=0.004). In contrast to NHL, PPM1D was not significantly mutated in MM (40% vs. 3.3%). 27 patients (4.3%) developed a second hematological malignancy at median of 4 years [1-10] post ASCT, of which 10 had CHIP. 22% received at least 3 years [0.06-12.8] of IMiD maintenance. Among those who did not receive IMiD maintenance, CHIP was associated with worse progression free survival (PFS) (p=0.047) where PFS at 3 years post ASCT was 31% (95%CI: 25-38) for those without CHIP vs. 15% with CHIP (95%CI: 7-25). In patients with IMiD maintenance, CHIP had no effect on PFS or overall survival (OS) (p=0.9). In patients with CHIP, receiving IMiD was associated with a better OS and PFS below the age of 58 and better PFS only in those above 58. In the overall cohort, CHIP was not associated with more adverse outcomes, which could be attributed to low OS and PFS in MM or the use of IMiD in 56% of this cohort. IMiD maintenance was associated with better OS (p&amp;lt;0.001) and PFS (p&amp;lt;0.001), consistent with prior studies, even in the presence of CHIP mutations. Conclusion: CHIP is a common entity among MM patients that predicts a worse PFS in those who do not receive IMiD maintenance therapy post ASCT. The use of IMiDs abrogated the deleterious effect imposed by CHIP in this cohort. Larger cohorts with longer follow up are needed, especially in the era of novel agents and long-term use of Lenalidomide maintenance. Citation Format: Tarek H. Mouhieddine, Jihye Park, Robert Redd, Christopher J. Gibson, Salomon Manier, Amin Nassar, Kalvis Hornburg, Marzia Capelletti, Daisy Huynh, Romanos Sklavenitits Pistofidis, Mark W. Bustoros, Saud H. AlDubayan, Brendan Reardon, Cody J. Boehner, Henry Dumke, Chia-Jen Lui, Darlys Schott, Eliezer M. Van Allen, Robert L. Schlossman, Nikhil C. Munshi, Kenneth C. Anderson, David P. Steensma, Jacob P. Laubach, Paul G. Richardson, Jerome Ritz, Benjamin L. Ebert, Robert J. Soiffer, Donna Neuberg, Irene M. Ghobrial. Immunomodulator maintenance post autologous stem cell transplant predicts better outcome in multiple myeloma patients with clonal hematopoiesis of indeterminate potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2954.

Update on the role of lenalidomide in patients with multiple myeloma

Lenalidomide is a derivative of thalidomide and belongs to the class of drugs known as the immunomodulatory drugs (IMiDs). The IMiDs have played a large role in improving the survival outcomes of patients with multiple myeloma. In particular, lenalidomide is currently standard of care in the newly diagnosed setting, in the maintenance setting post-autologous stem cell transplant, as well as in the relapsed/refractory setting. While the combination of lenalidomide and various proteasome inhibitors has proven particularly effective, there are emerging data demonstrating the effectiveness of lenalidomide in combination with other important classes of drugs including the monoclonal antibodies. Recent studies have provided insight into the molecular target of lenalidomide and the other IMiDs, although there is still much to be learned regarding the mechanisms by which lenalidomide affects the myeloma cell and the immune system. Here we review the molecular mechanisms of action, side effects, and the results of the clinical trials which have led to the widespread incorporation of lenalidomide into the myeloma therapeutic armamentarium.

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

BackgroundMultiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance.Methods/designACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively.All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression.DiscussionThe question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM.Trial registrationISRCTN, ISRCTN10038996. Registered on 15 December 2016.

The evolution of stem-cell transplantation in multiple myeloma.

Autologous stem-cell transplantation (ASCT) remains an integral part of treatment for previously untreated, and may have value in the treatment of relapsed patients with, multiple myeloma (MM). The addition of novel agents like immunomodulators and proteasome inhibitors as induction therapy before and as consolidation/maintenance therapy after ASCT has led to an improvement in complete response (CR) rates, progression-free survival (PFS) and overall survival (OS). With advances in supportive care, older patients and patients with renal insufficiency are now able to safely undergo the procedure. The data concerning the timing of ASCT (early in the disease course or at first relapse), single versus tandem (double) ASCT and the role and duration of consolidation and maintenance therapy post ASCT remain conflicting. This review aims to discuss the evolution of stem-cell transplant over the past 3 decades and its current role in the context of newer, safer and more effective therapeutic agents.

496 - Eltrombopag Treatment for Primary and Secondary Thrombocytopenia Post Allogeneic and Autologous Stem Cell Transplantation is Effective and Safe

Background: Approximately 5-25% of patients experience inadequate or delayed platelet (primary) recovery following stem cell transplantation (SCT). A few will experience secondary thrombocytopenia, defined as thrombocytopenia after initial platelet recovery without the relapse of decrease. Eltrombopag is a small molecule, thrombopoietin receptor agonist which has been approved for use in Immune thrombocytopenia purpura (ITP) and aplastic anemia. We evaluated our single center experience with safety and efficacy of Eltrombopag in post autologous and allogeneic stem cell transplant recipients. Methods: Between Sept 2014 to May 2017 we retrospectively evaluated 19 patients post autologous and allogeneic SCT for primary and secondary thrombocytopenia. Primary thrombocytopenia was defined as inadequate platelet recovery >20 × 109/L after 21 days requiring transfusions and secondary thrombocytopenia as thrombocytopenia <50 × 109/L after an initial engraftment above 50 × 109/L without transfusions. All patients placed on Eltrombopag had a normal liver function tests (Abormal liver function tests were considered if AST or ALT ≥ 2.5 ULN, or Bilirubin >2 mg/dl). Starting dose was either 25 or 50 mg per day and dose adjustments were per manufacturer's package insert. The primary endpoint was platelet recovery to ≥50,000/mL for 7 consecutive days without transfusion support. Results: Nineteen post-transplant patients were evaluated (Table 1). The median platelet count at the start of treatment was 17 × 109/L. The median time to start of Eltrombopag was 57 days and the median time to primary end point was 41 days. Overall response rate (ORR) in both cohorts was 74%. Six AUTO SCT patients received eltrombopag with 100% response rates. Among the 13 ALLO SCT recipients, 8 patients (61%) responded. The benefit of treatment was seen in patients with adequate and decreased megakaryocytic (MegaK) population (60 and 67% respectively; Figure 1). Both primary (n = 4) and secondary (n = 4) thrombocytopenic patients responded. Transient LFT and bilirubin elevations were noted in 6 patients in both cohorts without the need for discontinuation.Table 1Patient characteristicsFigure 1Promacta response in Allogeneic and Autologous recipientsView Large Image Figure ViewerDownload Hi-res image Download (PPT) The use of Eltrombopag in allogeneic recipients appeared to correlate with increased mortality, as 10 of 13 (77%) allogeneic recipients ultimately passed away from infections (40%), GVHD (40%) or relapse of disease (20%). Conclusion: Eltrombopag improves platelet recovery in in both AUTO and ALLO SCT recipients. In ALLO recipients, Eltrombopag exerted its effect regardless of the Megakrayocytic reserve, however its use correlated with worse outcome in those patients.

403 - Effect of Non Weight-Based Filgrastim Dosing on Engraftment in Autologous Stem Cell Transplantation

Background: The use of granulocyte colony stimulating factor (G-CSF) is currently recommended for use after autologous stem cell transplant by the American Society of Clinical Oncology Clinical Practice Guideline. The rationale behind the use of G-CSF is to decrease duration of neutropenia with the goal of reducing hospital length of stay and risk of infection. Most studies demonstrating a benefit for the use of G-CSF post-autologous stem cell transplant use a dose of 5 mcg/kg/day rounded to nearest vial size. The purpose of this study is to determine whether a flat dose of 300 mcg/day may be used for all patients, regardless of body weight, without affecting time to neutrophil engraftment, which could have implications for costs and resource utilization. Objective: The primary objective of this study was to determine whether there is a difference in time to engraftment, defined as ANC≥500 cells/microL for 3 consecutive days, in patients ≥78 kilograms versus patients <78 kg, using 300 mcg of filgrastim subcutaneously daily for all patients. This weight cutoff was chosen to divide patients into groups that would normally receive 300 mcg or 480 mcg, using a weight-based dose of 5 mcg/kg/day. Secondary objectives were to determine if there is a difference in hospital length of stay or the number of doses of G-CSF administered between the two groups. Methods: A retrospective chart review was conducted of subjects >18 years of age who received an autologous stem cell transplant between June 1, 2013 and May 31, 2016 and received filgrastim 300 mcg/day post-transplant. Data collected included: gender, age, admission weight, indication for transplant, transplant conditioning regimen, date of transplant, stem cell dose, date G-CSF started, number of doses of G-CSF given, time to first day of ANC ≥ 500 cells/microL, time to engraftment, and date of discharge. Results: There were 135 patients in the ≥ 78 kg cohort and 97 subjects in the <78 kg cohort. The median time to engraftment was 14 days (P = .6747, Figure 1) and the median time to first ANC ≥ 500 cells/microL was 12 days (P = .6747) in each cohort. The length of hospitalization was not significantly different (P = .16). The median number of G-CSF doses was 6 regardless of weight. Multivariate regression demonstrated that stem cell dose was the only independent variable associated with time to engraftment. Conclusions: There was no difference in time to engraftment or time to first ANC ≥ 500 cells/microL in patients >78 kilograms versus patients <78 kg using a flat dose of 300 mcg/day of filgrastim, nor was there a difference in median number of G-CSF doses. The total estimated cost savings in this population of 135 patients ≥78 kg, using flat dosing of 300 mcg of filgrastim instead of 480 mcg, was $73,200.