Date Of Autologous Stem Cell Transplantation Research Articles

Outcomes for Patients with Classical Hodgkin Lymphoma Who Relapse after Autologous Stem Cell Transplant in the Era of Novel Therapies

Background: For patients with relapsed and refractory (R/R) classical Hodgkin lymphoma (HL), the standard of care remains salvage therapy followed by autologous stem cell transplant (ASCT) for responding patients. Historical data suggest 40% of patients may relapse after ASCT, and these patients have generally a poor median overall survival (OS) of less than 2 years (Moskowitz et al., Br J Haematol. 2009;146(2):158-62). However, since these reports, the treatment landscape of R/R HL has dramatically improved, most notably with the introduction of two novel therapies, brentuximab vedotin (BV) and anti-PD1 agents. To refine our understanding of clinical outcomes in this context, we characterized patients who relapsed after ASCT in the modern era. Methods: We used a multicenter retrospective patient database at 5 transplant centers in the United States to identify patients with HL aged ≥ 12 years at diagnosis who had received ASCT on or after 1/1/2010. The primary objective was to determine the median OS for patients who relapsed after ASCT (post-ASCT-relapse OS), defining survival as the time from relapse after ASCT to subsequent death from any cause. Univariable Cox regression was performed to evaluate the impact of various factors on post-ASCT OS. Outcomes by era were evaluated using three different eras based on approval dates of novel agents: (1) pre-BV approval (pre-7/31/2011), (2) post-BV approval (8/1/2011-4/30/2016), (3) post-anti-PD1 approval (5/1/16-present). Results: A total of 215 patients were identified. The median age at ASCT was 34. Before ASCT, 128 patients (62%) had no exposure to novel agents, 76 patients (35%) had received BV and no anti-PD-1 therapy, and 11 patients (5.1%) had received anti-PD-1 therapy with or without BV. Conditioning was mostly with BEAM (59%) or CBV (32%). The median time to relapse after ASCT was 6 months (range: 1-109 months). Nearly half all relapses (47%) occurred within 6 months of ASCT. Only 14% of relapses occurred after 1 year. Among 126 patients with available treatment information, the median number of post-ASCT lines of therapy was 2 (IQR: 1, 4). Therapy for post-ASCT relapse included BV and no anti-PD-1 therapy in 41 patients (29%), anti-PD-1 therapy with or without BV for 70 patients (50%), and no novel agents for only 15 patients (11%). The median followup time from the date of ASCT among survivors was 5.0 (IQR: 2.8, 7.8) years. The median post-ASCT-relapse OS was not reached ( Figure 1). The 2- and 5-year post-ASCT-relapse OS were 75% (95% CI: 70%-81%) and 59% (95% CI: 53%-67%), respectively. On univariable Cox regression for post-ASCT-relapse OS ( Table 1), time to relapse greater than 6 (HR 0.55, 95% CI 0.35-0.85) or 12 months (HR 0.53, 95% CI 0.29-0.96) were significantly associated with improved post-ASCT-relapse OS. Increasing age at relapse was associated with worse OS (HR 1.05, 95% CI 1.04-1.07). Receipt of a novel agent (compared to chemotherapy alone) as the first salvage regimen for post-ASCT relapse was associated with improved post-ASCT OS (BV: HR 0.43, 95% CI 0.20-0.96; anti-PD-1: HR 0.44, 95% CI 0.18-1.08). Outcomes improved over time as regulatory approvals for novel agents occurred (post-BV-approval: HR 0.70, 95% CI 0.39-1.24; post-anti-PD-1 approval: HR 0.45, 95% CI 0.23-0.91). Conclusion: We show prolonged overall survival post-ASCT relapse compared to historical data likely due to the introduction of BV and anti-PD1 agents. This report represents one of the largest datasets of post-ASCT relapse in cHL, and this data should serve as an updated benchmark for future evaluations.

Clinical Outcomes in Patients with Mantle Cell Lymphoma Who Received Autologous Stem Cell Transplant in the Second Line Setting

Background: Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with a variable clinical outcome. The standard of care for transplant-eligible patients has been to employ autologous stem cell transplant (ASCT) in first remission and this strategy is currently being tested in the NCTN trial EA4151. The utilization and outcomes of ASCT in second line (2L) treatment is unclear and this knowledge is important for those in the non-transplant control arm in EA4151. In this report, we studied the outcomes of patients who received ASCT in 2L for relapsed/refractory (R/R) MCL. Methods: Patients with newly diagnosed MCL between August 2002 and April 2015 were enrolled in the Mayo Clinic/University of Iowa Lymphoma SPORE Molecular Epidemiology Resource (MER) prospective cohort study. Patients who received ASCT at 2L, or at 1L as a reference group, were included in this study. Clinical characteristics and treatment details were abstracted from MER and by additional chart review. Event-free Survival (EFS) was defined as time from ASCT to progression, retreatment, or death due to any cause, and overall Survival (OS) was defined as time from ASCT to death due to any cause. Survival rates were generated using the Kaplan-Meier method in Rv4.1.2. Results: Among a total of 343 patients with MCL enrolled in the MER, 177 had disease progression or relapse following 1L therapy and had complete 2L treatment information available. Eighteen patients were considered for ASCT as part of 2L therapy. Two (11%) patients did not have an adequate response to 2L induction therapy, and 1 (6%) patient did not meet criteria due to failure of the stem cell mobilization and harvest. Therefore, 15 (83%) patients went on to receive ASCT at the 2L. For the 15 patients who received ASCT at 2L, 1L therapies were R-CHOP (N=9, 60%), rituximab and bendamustine (R-bendamustine, N=2, 13%), rituximab and cladribine (N=3, 20%); 1 (7%) received surgical intervention. All 15 patients were considered for ASCT at 1L. Eight (53%) did not proceed due to inadequate response or progression of disease in the 1L setting; 2 (13%) were treated on clinical trials at 1L that precluded ASCT (one with R-CHOP with 90Yibritumomab tiuxetan and the other with R-Bendamustine); 2 (13%) were considered low risk for relapse and deferred ASCT, and 1 (7%) decided not to proceed (patient decision); the reason was unclear in 2 (13%) other patients. The median time from diagnosis to 1L disease progression/relapse was 6.4 months (range 1.1-35.8). Of the 15 patients who received ASCT as 2L therapy, the median age at time of ASCT was 58 years old, 14 (93%) were male, 13 (87%) had stage III/IV disease, and MCL international prognostic index (MIPI) score was low in 5 (63%) and intermediate in 3 (38%) (MIPI missing in 7 patients). Induction therapy at 2L prior to ASCT included R-CHOP alternating with R-DHAP (N=1, 7%), Hyper-CVAD (N=2, 13%), R-CHOP (N=3, 20%), R-DHAP (N=2, 13%), R-EPOCH (N=1, 7%), ROAD (N=1, 7%), R-ICE (N=1, 7%), R-bendamustine (N=3, 20%), and ibrutinib (N=1, 7%). At a median follow-up of 6.3 years from transplant for patients receiving ASCT at 2L, 9 patients had disease progression or relapse, and 8 patients died (3 without known progression or relapse). The median EFS was 3.8 years and the 2-year EFS rate was 59% (CI 38-91%) and 5-year EFS rate was 37% (CI 18-73%). The 2-year OS rate was 73% (CI 54-99%) and 5-year OS rate was 60% (CI 41-91%). As a reference, 113 patients in the MER received ASCT in the 1L setting. The median EFS from date of ASCT was 5.2 years and the 2-year EFS rate was 77% (CI 70-85%) and the 5-year rate was EFS 54% (CI 45-64%). The 2-year OS rate was 86% (CI 80-93%) and 5-year OS rate was 79% (CI 72-87%). Conclusion: ASCT consolidation after salvage therapy in the 2L setting appeared feasible in select patients with R/R MCL. The PFS and OS outcomes following 2L appeared reasonable. In the evolving landscape of R/R MCL treatment, it is unclear whether ASCT will still have a role. It is possible that select patients with R/R MCL would still benefit from ASCT. Larger studies, although likely limited to retrospective setting, are needed to further evaluate the feasibility, outcomes, and prognostic factors of ASCT at 2L and beyond. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment of Primary Plasma Cell Leukemia with Carfilzomib and Lenalidomide-Based Therapy: Results of the Final Analysis of the Prospective Phase 2 EMN12/HOVON-129 Study for Patients Aged 18-65 Years

Introduction. Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with a very poor prognosis. The median PFS for transplant-eligible patients (pts) is approximately 9 months. The aim of the EMN12/ HOVON-129 study was to improve the outcome of pPCL by incorporating carfilzomib and lenalidomide in induction, consolidation, and maintenance. The trial enrolled 61 pts aged 18 years and older, with different treatment for those aged 18-65 (n=36) and ≥66 years (n=25). Here we report the results of the final analysis for pts aged 18-65 years. Methods. The EMN12/HOVON-129 study is a prospective, non-randomized, phase 2, multicenter study, for previously untreated pPCL pts. Inclusion criteria were newly diagnosed pPCL (defined as >2x109/L circulating monoclonal plasma cells or plasmacytosis >20% of the differential white cell count) and WHO performance status 0-3. Main exclusion criteria were severe cardiac or pulmonary dysfunction; and creatinine clearance of <15 ml/min. There were no restrictions based on blood counts. Pts aged 18-65 years were treated with induction therapy with four 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd; carfilzomib 20/36 mg/m2 on days 1,2,8,9,15,16; lenalidomide 25 mg days 1-21; dexamethasone 20 mg on days 1,2,8,9,15,16,22,23). KRd induction was followed by tandem autologous stem cell transplantation (ASCT), 4 cycles of KRd consolidation, and then maintenance with carfilzomib (27 mg/m2 on days 1,2,15,16) and lenalidomide (10 mg on days 1-21/28 days) until progression. Pts who were eligible for allo-SCT, could also receive one ASCT, followed by 2 KRd consolidation cycles, reduced-intensity conditioning allo-SCT, and carfilzomib/lenalidomide maintenance. The primary endpoint was PFS, and secondary endpoints were response rate, OS, and toxicity. Results. From October 2015 till August 2021, we enrolled 36 pts with pPCL aged ≤65 years. Median age was 60 years; 67% had bone disease; and WHO performance status was ≥2 in 33% of pts. Pts had a high tumor burden with a median plasma cell percentage in BM of 80%. The median peripheral blood plasma cell count was 4.1x109/L (range 1.6-60.0); median platelet count was 111x109/L (range 20-517); and median eGFR was 54.0 ml/min (range 15.0-123). Pts had high-risk disease as evidenced by elevated LDH in 58%; and high frequency of high-risk genetic lesions (del(17p) in 47%, t(4;14) in 9%, t(14;16) in 19%, gain/ampl(1q) in 61%). Two or more high-risk cytogenetic abnormalities were present in 38%. The frequency of t(11;14) was 26%. In addition, 17% of pts had extramedullary plasmacytomas. ISS stage 3 was present in 64%, and revised ISS stage 3 in 50%. Response to induction was ≥PR in 72%, ≥VGPR in 64%, and ≥CR in 14%. Twenty-four pts (67%) received high-dose melphalan (HDM)/ASCT; 12 pts (33%) underwent a second course of HDM/ASCT; and 5 (14%) received allo-SCT after first HDM/ASCT. Eighteen pts (50%) received maintenance treatment. Best response on protocol was ≥PR in 83%, ≥VGPR in 81% and ≥CR in 50%; 10 (28%) pts achieved MRD-negative (10-5) CR. With a median follow-up of 40.8 months (range 8-2-74.5), the median PFS was 15.5 months (95% CI 9.4-38.4), which was sufficient to reject our null hypothesis (median PFS=9 months). With 19 pts having died (14 due to disease progression, 4 due to infections, and 1 due to cardiac disorder), median OS was 28.4 months (95% CI 15.1-not reached). In exploratory analyses, the presence of elevated LDH, t(14;16), and del(17p) were associated with both inferior PFS and OS. For patients who underwent first HDM/ASCT, median PFS and OS were 32.9 and 34.1 months from date of ASCT, resp. Adverse events mainly occurred during the first cycle of KRd, and decreased thereafter. Overall, grade ≥3 adverse events were observed in 67% of pts, including infections (25%) and cardiovascular disorders (14%). One patient developed a second primary malignancy (MDS). As of July 24 2022, 25 pts (69%) pts discontinued protocol treatment, mainly because of progression, but none because of treatment-related toxicity. Conclusions. KRd induction provides efficient and rapid disease control, which allows two-thirds of pts to undergo a first course of HDM/ASCT. Toxicity occurred mainly during the first cycle of induction, and was manageable with appropriate interventions. However, median PFS and OS remain low in pPCL, compared to MM. This trial was registered at https://trialsearch.who.int as NTR5350 Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Are We Choosing Mobilization Regimens for Autologous Stem Cell Transplantation in Multiple Myeloma Wisely?: A Single Centre Comparison of GCSF+/-Plerixafor Vs Cyclophosphamide/GCSF+/- Plerixafor

Background: Autologous stem cell transplantation (ASCT) as consolidation post induction is standard of care for eligible multiple myeloma patients. Multiple strategies are employed for mobilization of stem cells in ASCT. Cyclophosphamide/GCSF is an effective standard regimen. However there are reported toxicities associated with cyclophosphamide including risk of febrile neutropenia. Since plerixafor was introduced in Canada, this mobilization agent has been increasingly used as needed with GCSF at Kingston Health Science Centre (KHSC), with elimination of cyclophosphamide. There is however high cost associated with plerixafor. To date, there is no standard mobilization regimen across Canada. This retrospective study evaluates mobilization and ASCT outcomes of multiple myeloma patients who had undergone stem cell mobilization with GCSF+/-plerixafor (GP) vs cyclophosphamide/GCSF+/-plerixafor (CyGP) at KHSC. The goal is to analyze the efficacy of each regimen balanced with adverse events to guide optimal mobilization regimen choice. Method: Patient with multiple myeloma who had ASCT at KHSC were selected consecutively based on date of ASCT in a reverse chronological order starting from Jan 2019. From Oct 2015 to March 2018, CyGP was the mobilization regimen used at KHSC. From March 2017 to January 2019, cyclophosphamide was eliminated and GP was used. Both groups could have received plerixafor as needed based on Cancer Care Ontario funding criteria such as failure to achieve target CD34+ cell count. Retrospective chart review was conducted to collect data on demographics, plerixafor use, days of apheresis, total cell collected, rate of febrile neutropenia, length of transplant hospital stay, time to engraftment, and transfusion requirement. Chi-Square, t-test, or Mann Whitney methods were used for test of statistical significance where appropriate. Results: Total 97 patients were included with 47 in the GP group and 50 in the CyGP group (Table 1). Average age was 64 and 63 respectively. 32% of patients in GP group and 36% of CyGP group required plerixafor rescue. No difference in the number of apheresis days were noted in the two groups. Total cell collection was significantly higher in the CyGP group (P&lt;0.001). Day 1 and 2 cell collections were also significantly higher in the CyGP group (P&lt;0.05) (Fig 1). The cell dose target varied in the CyGP group due to changing practices over time which is a confounding factor. There were no cases of febrile neutropenia in the GP group and 3 cases in the CyGP group (P=0.243). All 3 febrile neutropenia patients required hospitalization with 1 requiring ICU. There was no clinically significant difference in transfusion requirement during ASCT (Fig 2). Median time to engraftment of neutrophil and platelet after ASCT were less by 1 day in the CyGP group (P&lt;0.05) (Fig 3), although there was no difference in length of transplant hospital stay. Conclusions: Stem cell mobilization with CyGP resulted in significantly higher total collection cell count, and more efficient collection with higher yield on the first 2 days of apheresis. However, there was no difference in the total number of apheresis days. It also did not lead to less plerixafor usage and was associated with possibly higher rate of febrile neutropenia. There was no clinically significant difference in transplant outcomes in terms of transfusion support required, days to engraftment, or length of hospitalization for ASCT. Mobilization with GCSF+/-plerixafor without cyclophosphamide is a non-inferior regimen. Disclosures Bhella: Celgene: Consultancy, Honoraria.

PB2125 THE IMPACT OF RVD OR VCD INDUCTION ON RESPONSE 3 MONTH AFTER FIRST LINE AUTOLOGOUS STEM CELL TRANSPLANT IN MULTIPLE MYELOMA. A SINGLE_CENTER RETROSPECTIVE ANALYSIS

Background:The use of triple agent induction therapy before first line high‐dose therapy (HDT) and autologous stem cell transplant (ASCT) in multiple myeloma is now considered standard of care. Cross‐study comparisons show that the combinations of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) have the highest response rates (Malankody Nat Rev Clin Onc 2015).Aims:In recent years there has been a shift in choice of induction therapy from the VCD to the RVD regimen in our region. We have evaluated how this shift has affected depth of response 3 months after ASCT in all patients receiving first line HDT with ASCT in our region from January 1st, 2015, and how frequently our patients needed to change induction regimen, based on choice of first line therapy.MethodsAll patients receiving first line HDT with ASCT for multiple myeloma in our institution in the period from January 1st, 2015 to October 26th, 2019 were evaluated for the final analysis of response 3 months post‐ASCT. The patients received 3‐5 cycles of induction therapy before leukapheresis, HDT (melphalan 200 mg/m2) and ASCT. All patients received a follow‐up consultation in our institution 3 months post‐ASCT, where response was evaluated and recorded according to the IMWG 2016 response criteria.Age, sex, date of ASCT, the presence of high‐risk cytogenetics, ISS stage at diagnosis, choice of induction regimen and response 3 months post‐ASCT was recorded by the primary investigator (Table 1).Results:48.3% (125 patients) received VCD as first‐line induction therapy, while 37.5% (97 patients) received RVD. 12.0% (15 patients) in the VCD group changed induction therapy vs 5.2% (5 patients) in the RVD group. In the RVD group 87.5% (77 patients) achieved ≥VGPR vs 84.5% (93 patients) in the VCD group. In addition, 11.3% in the RVD group (8 patients) achieved PR, while 3.4% (3 patients) had disease progression (PD) 3 months after ASCT. In the VCD group, 13.6% (15 patients) achieved PR, while 1.8% (2 patients) had PD 3 months after ASCT (Table 2, Figure 1). 26% (32 patients) starting VCD induction therapy and 16% (16 patients) starting RVD achieved a response rate &lt;VGPR, or needed to switch induction regimen. We define this as a poor outcome (figure 2).Summary/Conclusion:RVD induction therapy before HDT with ASCT trended toward higher rates of at least VGPR compared to VCD induction (87.5% s 84.5%). The choice of RVD as first line induction therapy necessitated fewer changes of induction regimen due to insufficient response or unacceptable toxicities compared to VCD induction (5.2% vs 12.0%). Fewer patients receiving RVD induction achieved a “poor outcome”: Response &lt;VGPR or need to change induction regimen. These results should be confirmed in larger patient materials, and in prospective studies. Updated data with approximately 30 additional patients, mainly receiving RVD induction, will be presented at the EHA annual meeting if our abstract is selected for presentation.

Prognostic Variables of Progression Free Survival in Mantle Cell Lymphoma after Autologous Stem Cell Transplantation

Background Autologous stem cell transplant (ASCT) is frequently used as a consolidative therapy option after induction treatment in fit patients with mantle cell lymphoma (MCL) with the goal of prolonging the initial response duration. Despite recent advances there remains a subset of patients who experience early disease relapse after ASCT. We examined predictors of shortened progression-free survival (PFS) and post-relapse overall survival (OS) in a cohort of patients completing ASCT in first remission. Methods We evaluated MCL patients treated at 10 US academic medical centers. Eligible patients were treated from 2000 through 2017, and we collected information on demographic, clinical, and treatment-related variables of interest. Patients were then categorized into three post-ASCT PFS groups: 0-2 years, 2-5 years, and > 5 years, with PFS determined from the date of ASCT until progression or death from any cause. Patients followed for at least 5 years post-ASCT who were relapse free were included in the > 5 sub group. Associations were examined between groups and collected characteristics using chi-squared tests for categorical patient characteristics and ANOVA for numeric patient characteristics. The Kaplan-Meier method was used to estimate overall survival (OS) for each group, using time of relapse after ASCT as the starting point. Results Of 968 total MCL patients, 242 patients completed ASCT in first remission and either had a PFS event or were relapse-free for at least 5 years post-ASCT. Patients were 80% male, and the median age was 59 (Range: 29-83). The patients were divided into groups of post-ASCT PFS 0-2 years (n=74), 2-5 years (n=75), and more than 5 years (n=93). Post-ASCT PFS was shorter in patients with stage 4 disease (p=0.022), splenomegaly at baseline (p=0.005), and a lymph node size > 5 centimeters at baseline (p=0.043). Other variables were not significantly associated with PFS, including time to transplant and use of intensive therapy. Patients with 0-2 year PFS had a shorter median OS (22.1 months, 95% CI: 13.1- 38.1 months) in comparison to 2-5 year PFS (132 months, 95% CI: 36-132 months) and 5+ year PFS not reached (95% CI: 41.2 – N.A; Figure). Conclusion Patients with higher tumor burden at baseline have a shorter post-ASCT PFS and are more likely to relapse within 2 years. As has been seen in other lymphoma subtypes, early relapse is associated with shorter OS. This represents a patient group requiring improved therapies and perhaps are the best candidates for post-ASCT maintenance or consolidation approaches. Further studies integrating minimal residual disease and molecular risk-stratification may better identify patients at high risk for early progression.

Patterns of Relapse After Salvage Autologous Stem Cell Transplant for Hodgkin's Lymphoma: Should Sites of Relapse Relative to Initially Involved Sites Be Used to Guide Indications for Peri-Transplant Radiation Therapy

PurposeWe aimed to assess patterns of relapse in patients undergoing salvage autologous stem cell transplant (ASCT) for relapsed Hodgkin lymphoma in the modern era with the hypothesis that patients who suffer a relapse at initially involved sites are at increased risks of relapse post-ASCT that may help guide the application of peri-transplant radiation therapy. Methods and MaterialsA retrospective review was conducted of 38 patients undergoing ASCT between 2002 and 2017 for relapsed or refractory Hodgkin lymphoma. The site of relapse at the time of ASCT and subsequent relapses were compared with sites of the initial involvement at the time of diagnosis using follow-up imaging (most commonly positron emission computed tomography). Relapse and overall survival rates were calculated from the date of ASCT using the Kaplan-Meier method with a multivariate analysis, completed using a Cox multivariate analysis. ResultsThe median follow-up time was 38 months (interquartile range, 18-66 months). Twenty-two patients (58%) suffered a relapse after ASCT at a median time to relapse of 9.1 months (interquartile range, 2.9-12.3 months) with a 5-year risk of relapse of 58% (95% confidence interval [CI], 41%-75%). On univariate analysis, relapse at an initially involved site was significant for higher rates of relapse at 71% at 5-years (95% CI, 52%-90%) compared with relapse at initially uninvolved sites at 30% (95% CI, 2%-58%; P = .05). The relapse rate was also significantly higher in patients age <30 years at the time of diagnosis at 80% (95% CI, 59%-100%) compared with 40% (95% CI, 18%-62%) at 5 years in patients aged >30 years (P < .01). On multivariate analysis, relapse at initially involved sites was significant for higher rates of relapse (hazard ratio: 8.3; 95% CI, 1.2-57.4; P = .03). ConclusionsRelapses at initially involved sites may potentially increase the risk of relapse after ASCT. Additional studies are needed to clarify whether this should be used as an additional factor to guide recommendations for peri-transplant radiation therapy.

The Impact of RVD or VCD Induction on Response 3 Months after First Line Autologous Transplant in Multiple Myeloma. a Single-Center Retrospective Analysis

Introduction: The use of triple agent induction therapy before first line high-dose therapy (HDT) and autologous stem cell transplant (ASCT) in multiple myeloma is now considered standard of care. While thalidomide/bortezomib/dexamethasone (VTD) is the only induction regimen approved by EMA, both cyclophosphamide/bortezomib/dexamethasone (VCD) and lenalidomide/bortezomib/dexamethasone (RVD) are recommended in the most recent ESMO guidelines (Moreau et al., Annals of Oncology, 2017).Prospective comparisons of VCD and RVD are lacking. Cross-study comparisons show that the combinations of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) have the highest response rates (Malankody Nat Rev Clin Onc 2015).In recent years there has been a shift in choice of induction therapy from the VCD to the RVD regimen in our region. We have evaluated how this shift has affected depth of response 3 months after ASCT in all patients receiving first line HDT with ASCT in our region from January 1st, 2015, and how frequently our patients needed to change induction regimen, based on choice of first line therapy.Methods: All patients receiving first line HDT with ASCT for multiple myeloma in our institution in the period from January 1st, 2015 to March 16th, 2018 were evaluated for the final analysis of response 3 months post-ASCT. The induction regimen was chosen at their local physician´s discretion. The patients received 3-5 cycles of induction therapy before leukapheresis, HDT (melphalan 200mg/m2) and ASCT. All patients received a follow-up consultation in our institution 3 months post-ASCT, where response was evaluated and recorded according to the IMWG 2016 response criteria. No patients had started maintenance therapy at the time of evaluation. Age, sex, date of ASCT, the presence of high-risk cytogenetics, ISS stage at diagnosis, choice of induction regimen and response 3 months post-ASCT was recorded by the primary investigator (Table 1). In case of change of regimen during induction treatment, the reason was recorded. Patients receiving either VCD or RVD as induction therapy, who did not change regimen during induction, were included in the final response analysis.Results: 212 patients received HDT with ASCT in the period. 209 patients were evaluated 3 months after ASCT as of June 21st, 2018. 57.5% (122 patients) received VCD as first-line induction therapy, while 25.9% (55 patients) received RVD. 11.5% (14 patients) in the VCD group changed induction therapy vs 3.6% (2 patients) in the RVD group. Reasons for changing regimen were: not achieving at least a partial response (PR) (n=10), unacceptable toxicity (n=4), lack of documented reason (n=2). In the RVD group, 1 patient died from sepsis 2 weeks post-ASCT, and 1 patient refused to attend the post-ASCT evaluation. Therefore, 108 patients in the VCD group and 51 patients in the RVD group were included in the final response analysis.29 patients could not confirm a complete response (CR) due to lack of bone marrow and/or serum immunofixation at response evaluation. For that reason, patients achieving CR, unconfirmed CR and very good partial response (VGPR) were compounded to a ≥VGPR response grade.In the RVD group 94,1% (48 patients) achieved ≥VGPR vs 85,2% (92 patients) in the VCD group. Similar differences were also present for confirmed CR (25% vs 18%) and unconfirmed CR (44% vs 35%). In addition, 2% in the RVD group (1 patient) achieved PR, while 3.9% (2 patients) had disease progression (PD) 3 months after ASCT. In the VCD group, 13.0% (14 patients) achieved PR, while 1.8% (2 patients) had PD 3 months after ASCT (Table 2, Figure 1).Discussion: RVD induction therapy before HDT with ASCT yielded higher rates of at least VGPR compared to VCD induction (85,2% s 94,1%). The choice of RVD as first line induction therapy necessitated fewer changes of induction regimen due to insufficient response or unacceptable toxicities compared to VCD induction (3,6% vs 11,5%). The differences were not statistically significant, possibly because of too few patients. Still, our results support the trend in our region of choosing RVD as first-line induction for transplant-eligible patients. These results should be confirmed in larger patient materials, and in prospective studies.Updated data with approximately 35 additional patients, mainly receiving RVD induction, will be presented at the ASH annual meeting if our abstract is selected for presentation. [Display omitted] DisclosuresMoksnes:Shire: Consultancy. Schjesvold:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy; Bayer: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy; Abbvie: Honoraria; Adaptive: Consultancy; Novartis: Honoraria.

Three Decades of Autologous Stem Cell Transplantation for Myeloma; Trends in Early Mortality and Survival

Introduction: Outcomes in multiple myeloma have significantly improved in recent times owing to the availability of newer more effective therapies. Autologous stem cell transplantation (ASCT) has been used for over three decades to treat multiple myeloma. We aimed to evaluate the outcome of patients receiving ASCT at our institution between 1990 and 2015.Patients and Methods: A total of 2025 patients received ASCT at Mayo Clinic Rochester between 1st January 1990 and 31st December 2015. The patients were divided in to three cohorts of approximately equal time period, Cohort 1 (1990-1999, n=144), Cohort 2 (2000-2009, n=909) and Cohort 3 (2010-2015, n=972). Outcomes of interest were early mortality, progression free survival (PFS) and overall survival (OS). Disease characteristics were documented from time of diagnosis and PFS and OS were calculated from date of ASCT unless otherwise stated.Results: Median age for the whole cohort was 60 years (range 24-77) and increased over time (55 Cohort 1 vs 59 Cohort 2 vs 61 Cohort 3, p<0.0001). The proportion of males (60% for whole cohort) was not significantly different between the 3 time periods. Almost all patients (99%, n=2018) received chemotherapy prior to transplantation (median lines of therapy 1, range 0-6). The number of patients receiving >1 line of therapy prior to transplantation decreased over time (67% Cohort 1 vs 27% Cohort 2 vs 34% Cohort 3, p<0.0001). The use of novel agents was congruous with their availability and increased over time (0% Cohort 1 vs 59% Cohort 2 vs 100% Cohort 3, p<0.000).After a median follow up of 84 months (95% CI, 78-91 months), median PFS and OS for the whole cohort were 24 and 66 months respectively. Both PFS and OS improved significantly over time (median PFS: 12 months Cohort 1vs 18 months Cohort 2 vs 33 months Cohort 3, p<0.0001; median OS: 26 months Cohort 1vs 63 months Cohort 2 vs 83 months Cohort 3, p<0.0001), Figure 1. The improvement in PFS and OS over the 3 time periods was seen in patients receiving early (≤ 12 months from diagnosis) and delayed (>12 months) ASCT, Table 2. OS from diagnosis was no different for early versus delayed transplant in Cohort 1 and Cohort 2 (Cohort 1: median OS 57 months for early vs 56 months for delayed, p=0.24 and Cohort 2: median OS 81 months for early vs 82 months for delayed, p=0.70) and showed a trend towards a marginal benefit for delayed transplant in Cohort 3 (median OS 105 months for early vs 109 months for delayed, p=0.046).Treatment related mortality (100 days post transplant) improved over time (7.6% Cohort 1 vs 1.8% Cohort 2 vs 0.7% Cohort 3, p<0.0001), Figure 2A. Mortality within 12 months of ASCT also improved over time (24% Cohort 1vs 8% Cohort 2 vs 6% Cohort 3, p<0.0001). A landmark analysis of OS from 12 months post ASCT continued to reveal improved survival over time(median OS 26 months Cohort 1vs 63 months Cohort 2 vs 83 month Cohort 3, p<0.0001), Figure 2B.Conclusion: ASCT remains an important therapeutic option for eligible patients with multiple myeloma. There has been a marked improvement over time in PFS and OS and reduction in treatment related mortality and early mortality in myeloma patients receiving ASCT. This is likely to reflect the addition of novel agents to induction regimens and improved post transplant therapies. Despite these improvements myeloma remains incurable with patients continuing to relapse and die many years after ASCT. [Display omitted] DisclosuresDispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Lacy:Celgene: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gertz:Research to Practice: Consultancy; Physicians Education Resource: Consultancy; Amgen: Consultancy; spectrum: Consultancy, Honoraria; celgene: Consultancy; annexon: Consultancy; janssen: Consultancy; Alnylam: Honoraria; Abbvie: Consultancy; Ionis: Honoraria; Teva: Consultancy; Apellis: Consultancy; Medscape: Consultancy; Prothena: Honoraria.

Lenalidomide Maintenance after Autologous Stem Cell Transplant in Patients with High-Risk Relapsed/Refractory Lymphomas Is Feasible and Compares Favorably to Historical Controls: Results of a Phase I/II Trial

Background: Lymphoma patients with residual hypermetabolic lesions on FDG-PET imaging after salvage chemotherapy have poor outcomes following autologous stem cell transplant (ASCT). We have previously shown progression free survival (PFS) of only 5 months (range: 1-19) in this population with only 7% of patients without progression at 12 months (Svoboda et al, BMT 2006). We hypothesized that these high-risk patients may benefit from continued therapy after ASCT. Lenalidomide is an immunomodulatory agent which has been used as maintenance in other hematologic malignancies, but its toxicity and efficacy have not been well described in lymphoma patients following ASCT.Methods: We are conducting a phase I/II prospective, open-label trial of lenalidomide maintenance after ASCT in lymphoma patients at high risk for relapse defined by residual FDG-PET positive lesions (SUV ≥ 2.5) immediately prior to ASCT. The primary objective of phase I was to determine the safety and dose-limiting toxicity (DLT) of lenalidomide maintenance. A 3+3 de-escalation design was used with a starting dose of lenalidomide at 10 mg on days 1 through 28 of each 28-day cycle. Lenalidomide was initiated 28-100 days post-ASCT and planned for up to 24 cycles. DLT was defined as non-hematologic toxicity ≥ grade 3 or hematologic toxicity ≥ grade 4 during the first 28 days of lenalidomide. The primary objectives of phase II were PFS and overall survival (OS). Survival outcomes were calculated from the date of ASCT. Enrollment began in 5/2012; we report data through 7/2016.Results: Fourteen patients were enrolled and 11 were evaluable (one patient withdrew consent and two progressed prior to initiation of lenalidomide). Eight (73%) evaluable patients had diffuse large B-cell lymphoma (DLBCL): 4 with germinal center (GC) origin and 4 non-GC by Hans algorithm. Three (27%) patients had Hodgkin lymphoma. Median age was 44 years (29-61), ECOG PS 0 (0- 1), prior therapies 2 (2-5). Median follow-up was 24 months (range 8-44), and median time on lenalidomide was 13 cycles (1-24). No DLTs were observed in phase I, and the dose of 10 mg daily was determined to be appropriate for phase II. Six (55%) patients discontinued lenalidomide: 3 due to disease progression, 2 at investigator’s discretion (1 subsequently progressed), and 1 due to grade 3 rash possibly related to lenalidomide. Of 3 patients who discontinued lenalidomide due to progression, 1 (non-GC DLBCL) died of disease progression, 1 (GC DLBCL) achieved complete remission (CR) with allotransplant, and 1 (non-GC DLBCL) remains on another active therapy. Overall, 8 (73%) patients remain in CR following ASCT, including 3 patients who discontinued lenalidomide. Of note, 1 patient developed adenocarcinoma of the colon 1 year after completion of lenalidomide, and 1 patient developed therapy-related acute myeloid leukemia at 10 months after discontinuing lenalidomide. At a median follow-up of 24 months, PFS of the complete cohort was 62.3% (95% CI: 0.28-0.84; Figure 1) and median PFS was not reached. OS was 75% (95% CI: 0.30-0.93; Figure 2) and median OS was not reached. When compared to the reported PFS of 7% at 12 months in the historical controls with identical high risk pre-transplant characteristics, the PFS of 62.3% (95% CI: 0.28-0.84) at 12 months was significantly improved (Z-test, p<0.05).Conclusion: We established feasibility of lenalidomide maintenance at 10 mg daily after ASCT in patients with relapsed/refractory lymphomas. Preliminary clinical outcomes observed in this phase I/II trial are very encouraging when compared to historical controls. To better understand the toxicity profile and validate the promising clinical benefit, the strategy of utilizing immunomodulatory agents as post-transplant maintenance should be studied in a larger cohort of high-risk lymphoma patients. [Display omitted] [Display omitted] DisclosuresSvoboda:Pharmacyclics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding. Nasta:Millennium Pharmaceuticals: Research Funding. Mato:Abbvie: Research Funding; Acerta Pharma: Research Funding; Gilead Sciences: Research Funding; ProNAi: Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Consultancy; Theradex: Research Funding; TG Therapeutics: Research Funding; Gilead Sciences: Consultancy; Abbvie: Consultancy. Hwang:Novartis: Research Funding. Schuster:Janssen Research & Development: Research Funding; Gilead: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria; Hoffman-LaRoche: Research Funding; Merck: Research Funding.

Preliminary Results of FDG-PET Scanning after GDP Chemotherapy Prior to Autologous Stem Cell Transplant (ASCT) for Relapsed/Refractory (RR) Lymphoma

Introduction:Gemcitabine, dexamethasone and cisplatin (GDP) has become a standard salvage chemotherapy (SC) regimen for relapsed/refractory (RR) lymphoma prior to autologous stem cell transplantation (ASCT) (Crump JCO 2014). Response to SC is now evaluated using 18-Fluoro-deoxyglucose positron-emission-tomography (FDG-PET) scans based on the recent Lugano classification (Cheson JCO 2014). We evaluated the response of patients (pts) with Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) to GDP by PET-CT scans and attempted to determine whether PET was predictive of outcome.Methods:We performed a retrospective chart review of consecutive HL and DLBCL (diffuse large B-cell lymphoma) pts who underwent ASCT following GDP SC at our centre between January 2014 and July 2016. All pts previously received anthracycline-based chemotherapy (typically ABVD for HL or R-CHOP for NHL) for primary treatment. Pts underwent FDG-PET scans after 3 cycles of SC and scans were retrospectively reported with the Deauville Criteria Scale with Deauville scores of 1-3 considered negative, whereas scores of 4 or 5 represented a positive result. Response to GDP was documented with CT scans using 1999 Working group Criteria (JCO 1999). Pts proceeded to ASCT if they had a PR by CT imaging and no signs of PD on PET-CT. Post-PET radiation or additional chemotherapy could be given at the discretion of the treating physician. Progression free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method from the date of progression or date of ASCT. Statistical analysis to determine the significance of PET result on outcome was performed using the long rank test.Results: 45 pts with DLBCL and 29 pts with HL were identified: median age was 45 (range: 23-69) and 29 (range: 19-58) years respectively. Baseline patient characteristics are listed in Table 1. Following GDP SC, PET Deauville scores of 1-3 were reported in 55% of HL and 29% of DLBCL pts. Overall response rate to GDP by CT was 72% for HL pts and 64% for DLBCL pts (Table 2). For HL, 100% (16/16) of pts with a PET(-) scan and 91% (10/11) with a PET(+) result proceeded to ASCT. 85% (11/13) of DLBCL pts who had a PET(-) scan and 48% (15/31) with a PET(+) scan underwent ASCT. Additional therapy post PET scan included involved field radiation, additional chemotherapy (mini-BEAM) or novel therapy (brentuximab and bendamustine for HL patients). Median follow-up time was 14.2 months (HL) and 13.4 months (DLBCL) from relapse/progression after initial chemotherapy; and 9.6 months (HL) and 10.9 months (DLBCL) from ASCT. There was a statistically significant difference between PET(+) and PET(-) DLBCL patients from the time of initial disease progression for PFS (26% versus 69%, p=0.011) that did not reach statistical significance for OS (p=0.072). However, there was no significant difference for PFS and OS in DLCBL from ASCT when stratified by PET result (p= 0.154 and p=0.723 respectively). In HL pts, no statistically significant differences for PFS and OS from progression (p=0.480 and p=0.387 respectively) or from ASCT (p=0.579 and p=0.450 respectively) were found when stratified by PET result (see Tables 3 and 4).Conclusion: Deauville 4-5 PET scores appear to be predictive of PFS for RR-DLBCL pts. The lack of a significant difference between PET results for OS in DLBCL is likely due to sample size and the need for longer follow-up. For RR-HL pts, PFS and OS rates were both high but did not seem to noticeably differ by PET result. Additional therapy employed for Deauville 4-5 patients peri-ASCT could influence outcome. Overall, PET response assessment post GDP appears to stratify outcome in patients with DLBCL and PET adapted therapy in HL patients may improve outcome in Deauville 4-5 patients. Review of pending cases and subsequent follow-up is ongoing. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic Value of Pre-Transplant PET Scan in Patients with Diffuse Large B-Cell (DLBCL) Lymphoma Undergoing Autologous Stem Cell Transplantation (ASCT)

Background: Recent data have shown that pre-transplant FDG-PET is prognostic in DLBCL patients undergoing autologous stem cell transplantation (ASCT). We retrospectively analyzed data on patients with DLBCL treated with ASCT to assess the impact of pre-transplant FDG-PET on relapse-free survival (RFS) and overall survival (OS).Methods: We reviewed medical records of 32 patients with DLBCL who underwent ASCT using high dose busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP) at Cleveland Clinic from June 2008 to December 2012 and had both a relapse FDG-PET as well as a pre-transplant FDG-PET available for review. All images were interpreted by a staff nuclear medicine radiologist blinded to the outcomes. Visual analysis was performed using the Deauville five-point scale and semiquantitative analysis was done by measuring the maximum standardized uptake value (SUVmax). ΔSUVmax was calculated by determining the difference between the SUVmax at the time of relapse and the SUVmax immediately prior to transplant. Patients were grouped into pre-transplant Deauville score 1-3 or 4-5. Baseline characteristics were compared between groups using the Chi-square test or Wilcoxon rank test. Cox proportional hazards analysis was used to identify prognostic factors. Outcomes were calculated from the date of ASCT. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank testResults: The median age of the patients at transplant was 57 and 69% were male. There was no significant difference in baseline characteristics of patients who had a Deauville score 1-3 compared to patients who had a Deauville score 4-5 including mean age, gender, race, Karnofsky performance status, number of prior chemotherapy regimens, prior radiation therapy, and IPI at diagnosis and transplant. There was a trend towards significance in the median SUVmax at relapse in the Deauville 1-3 group compared to the Deauville 4-5 group (11.1 vs. 18.1, p=0.08) and a significant difference in the median pre-transplant SUVmax (2.3 vs. 8.1, p<0.001). Deauville score 4-5 was the only baseline variable that was prognostic for both RFS (HR=4.2, CI 1.6-11.5, p=0.004) and OS (HR=5.5, CI 1.6-18.9, p=0.006). The 3-year RFS for patients in the Deauville 1-3 group was 64% compared to 12% in the Deauville 4-5 group (p=0.002) and the 3-year OS for patients in the Deauville 1-3 group was 84% compared to 30%, respectively (p=0.002 [Figure 1]). The median ΔSUVmax was 74%. There was no difference in RFS or OS in patients who had a ΔSUVmax above or below this median. However, a high pre-transplant SUVmax(>6 vs. <6) was associated with significantly inferior RFS (p=0.03 [Figure 2]).Conclusions: Pre-transplant FDG-PET Deauville score is prognostic of RFS and OS in patients with DLBCL undergoing ASCT. High SUVmax(>6) prior to transplant is predictive of poor RFS. Pre-transplant PET is a powerful tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies. [Display omitted] [Display omitted] DisclosuresSmith:celegene, spectrum, genentech: Honoraria. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Non-Inferior Clinical Outcomes for Lymphoma and Myeloma Patients Referred from a County Hospital to an Academic Transplant Center for Autologous Stem Cell Transplantation

IntroductionDisparities in clinical care have been described for patients who have limited insurance coverage or social support. We hypothesized that patients with relapsed Hodgkin’s lymphoma (HL), non-Hodgkin’s lymphoma (NHL), or multiple myeloma (MM) treated at an urban county hospital for whom autologous stem cell transplant (ASCT) was indicated would face barriers for referral to a private academic transplant center, and would have inferior survival compared with similar patients treated primarily at the transplant center. We analyzed a series of patients with HL, NHL, or MM treated at the county hospital and determined referral rates, frequency of ASCT, and overall survival rates compared to similar patients treated primarily at the transplant center.MethodsFollowing IRB-approval, charts of consecutive patients with HL (n=39), NHL (n=96), or MM (n=80) treated at Grady Memorial Hospital, a county hospital of Atlanta, between 2007 and 2013 were reviewed. Abstracted data included clinical indication for ASCT by histology (MM patients, and relapsed patients with HL and NHL), reasons for non-referral, decision whether to offer ASCT at the academic center, and survival following referral. Censored data were used to calculate the follow up period for each group. Kaplan-Meier survival plots were generated for subsets of referred patients.ResultsA total of 215 patients with diagnosis of HD, NHL, MM were identified. Information for 12 (6%) patients was not available. The remaining 203 patients constituted the study group. 43 patients were referred for ASCT consults and 160 patients were not referred. Patients not referred for ASCT included: 21 (13%) with Karnofsky performance status (KPS) <60%; 71 (45%) in remission; 16 (10%) with NHL histology in which ASCT is not indicated including newly diagnosed follicular lymphoma, marginal zone lymphoma, peripheral T-cell lymphoma (PTCL), and chronic lymphocytic leukemia; 9 (6%) with refractory disease; 14 (9%) who refused referral, or who lost to follow up, or referred to a VA hospital; 5 (3%) who died before referral; 5 (3%) with age >70 years; 1 (1%) with psychosocial barriers; 6 (4%) who were illegal immigrants; 4 (3%) noncompliant to medical regimens; 2 (1%) with substance abuse; and 1 (1%) lacking adequate social support for ASCT. Among the 43 referred patients, 27 patients were transplanted, 16 were not transplanted. Among transplanted patients, 19 patients had MM, 5 had NHL, and 3 had HL. Reasons for non-transplant included: recommendation to continue conventional maintenance and chemotherapy for MM [n=5 (31%)]; comorbid conditions and KPS <60% [n=4 (25%)]; refractory/progressive diseases [n=4 (25%)]; disease not indicated for ASCT [n=2 (13%)] including PTCL, good response to the current chemotherapy in HL; and noncompliance with treatment [n=1 (6%)]. Two patients in the transplant group were excluded in the analysis of survival due to lack of data on the date of diagnosis. Median follow-up for all referred patients from the time of diagnosis was 4.2 [1.5-14.2] years including a follow-up of 3.3 years [1.5-14.2] in the transplant group, and 5.8 years [1.7-8.0] in non-transplant group. 8-year survival of transplanted patients from the date of diagnosis was 78.6% versus 48.8% for patients not transplanted. (log-rank test, p-value=0.14) (See figure). From the date of ASCT, 8-year survival of transplanted patients was 77.3%. Among transplanted patients, 8-year survival from the date of ASCT was 68.9% for MM patients with no deaths noted to-date in patients with NHL or HL who underwent ASCT. Post-transplant survival among referred patients was not inferior to post-transplant survival among patients treated primarily at the transplant center.ConclusionIn the era immediately prior to implementation of the Affordable Care Act (ACA), the process of referral of patients with MM, NHL, or HL from a county hospital to an academic tertiary care center for ASCT appeared appropriate, without significant barriers based upon insurance or social support status. Post-referral decisions whether to proceed to ASCT were made based upon established criteria. Post-ASCT survivals among referred patients were comparable or superior to those of patients treated primarily at the transplant center and published series. Further evaluation is needed to assess the impact of the ACA on access to ASCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Autologous stem cell transplantation for follicular lymphoma is of most benefit early in the disease course and can result in durable remissions, irrespective of prior rituximab exposure

The role of autologous stem cell transplantation (ASCT) and the optimal timing of such transplants in patients with follicular lymphoma (FL) remains contentious. We present a single-centre experience documenting the outcomes of 70 FL patients who underwent BEAM (carmustine, cytarabine, etopside, melphalan)-conditioned ASCT between 1988 and 2009. With a median follow-up of 6·8 years (0·1-19·2), the 7-year overall survival (OS) and progression-free survival (PFS) from the date of ASCT was 76% and 60%, respectively. A significant difference in OS was found when comparing the patients transplanted in first or second remission versus those transplanted in later remissions (P = 0·02) and this significance was maintained when OS was calculated from the date of diagnosis (P = 0·03). There was a plateau on the PFS curves for patients transplanted in either first or second remissions after 9·3 and 6·4 years respectively, suggesting that these groups may never relapse. No differences were seen in OS or PFS in those treated with rituximab prior to transplant versus those who were not. Our data shows that BEAM ASCT can be a highly effective treatment in patients with FL early in the disease course, and that a proportion of patients experience prolonged disease-free survival and may be cured.

The Impact of Different Pre-Transplant Regimens Including Novel Agents On Peripheral Blood Mobilization, Harvest, Response and Survival in Patients Undergoing ASCT for Multiple Myeloma. A Single-Center Experience in 210 Patients.

Abstract 2279Poster Board II-256High dose therapy (HDT) with autologous stem cell transplantation (ASCT) has become the standard of care for eligible patients with multiple myeloma (MM) younger than 65 years. Induction therapy with combination regimens such as VAD or single agent dexamethasone has little impact on SC mobilization and offers a PFS of 12-18 months post-ASCT. Recently, novel agents (IMiDs and bortezomib) are used in the induction regimens prior to ASCT. The aim of this study was to assess the impact of conventional and novel agent-based induction regimens on SC harvest, response and survival among patients with MM treated in the Department of Clinical Therapeutics of the University of Athens, Greece. From January 1996 to June 2009, 210 consecutive patients who underwent ASCT were classified according to the induction regimens to: those who had received conventional chemotherapy (CC) only (MP, CD or VAD) (group A); those who were treated with CC followed by novel agent-based regimens (dexamethasone plus an IMiD and/or bortezomib; group B); and patients who were treated with novel agent-based regimens only prior to SC collection (group C). Stem cells were mobilized with G-CSF alone or with cyclophosphamide and G-CSF. Group A included 102 (49%) patients, group B 72 (34%) and group C 33 (16%) patients. Induction with novel agents only (group C) yielded a significantly greater SC collection compared to induction with CC only (group A) or CC followed by novel agent-based therapies (group B) (p=0.006 and p=0.038, respectively). The mean number of collected CD34+ cells/kg was 10×106 (range 2-43.2×106), 10.4×106 (range 2-49×106) and 15.1×106 (range 2-65×106) for groups A, B and C, respectively. The probability to collect a number of at least 5×106 CD34+ cells/kg was significantly higher in patients who received novel agents only when compared to those of groups A and B (78.8% vs. 57.5%, p=0.021). Among patients of group A, those who received induction with VAD had a significantly greater SC collection when compared to MP or CD (mean CD34+ cells/kg collected: 12.2×106vs. 7.56×106 /kg; p=0.031). Moreover, SC yield did not differ between patients who received VAD only or novel agent-based regimens only, as induction therapy (p=0.155). Engraftment data were comparable between the three groups. Age >55 years (p=0.039) and prior radiation therapy (p<0.0001) negatively influenced SC collection. The administration of novel agent-based regimens alone was associated with superior response rate prior to ASCT compared to CC alone as induction therapy (objective response (OR) 87.5% vs. 61.7%, p=0.007; at least vgPR 27.2% vs. 18.9%, p=0.032, for groups C and A, respectively). However, post-ASCT, patients of groups A and C achieved similar response rates (OR: 94.6% vs. 92.9%, p=0.736 and at least vgPR: 53.6% vs. 46.7%, p=0.526). The median OS, from the date of ASCT, in all patients was 74 months. Factors associated with longer OS included the achievement of CR or sCR post-ASCT (p=0.027), ISS-1 and -2 vs. ISS-3 (p=0.007), low beta2-microglobulin (<3.5 mg/mL) prior to ASCT (p=0.023), low marrow infiltration by plasma cells (<5%) prior to ASCT (p=0.016) and normal MRI pattern at diagnosis (vs. focal and diffuse, p=0.027). The use of novel agent-based regimens in induction therapy was associated with a probability of 4-year OS of 88% compared to 54% in patients of group A. There was a trend in favor of novel agent-based regimens as induction therapy in terms of OS (median 89 vs. 62 months, for patients of groups B+C and A, respectively; p=0.144). Furthermore, patients of group C had superior EFS post-ASCT compared to patients of group A (median 84 vs. 27 months; p=0.046). Other variables like mobilization regimen before HDT (cyclo 4g/m2+G-CSF vs. cyclo 2.5 g/m2+G-CSF vs. G-CSF only), high dose therapy dosage (melphalan 200 mg/m2vs. 180 mg/m2vs. 140mg/m2 or less), and the interval from diagnosis to ASCT (more or less than one year) did not correlate with OS or PFS. In conclusion, our study demonstrates that patients who received induction therapy with novel agents only prior to ASCT had a higher number of CD34+ cells collected when compared to induction with CC followed by novel agent-based regimens or CC alone. Furthermore, these patients achieved a higher response rate and a better quality of response before HDT, compared to patients who received CC only, but this did not correspond to a higher response rate post-ASCT. Further follow-up is needed to fully assess the impact of novel agent induction on patient's OS. Disclosures:No relevant conflicts of interest to declare.

Age 40 Years and Under Does Not Confer Superior Prognosis in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transmplant

Multiple myeloma (MM) rarely occurs in patients 40 years of age and younger. This young age has been reported to correlate with improved survival in patients with MM. The objective of this study is to describe presenting features and outcomes of patients < or =40 years of age with MM who undergo autologous stem cell transplantation (ASCT) as first-line treatment, and compare overall survival (OS) and progression free survival (PFS) to patients aged 41-65 years. We performed a retrospective institutional review of all patients < or =40 years of age and 41-65 years of age at the time of diagnosis of MM who had undergone upfront ASCT from January 1, 1990, to July 31, 2007. Thirty-eight patients < or =40 years of age and 608 patients aged 41-65 were identified. There was a high rate of plasma cell leukemia (PCL) in young patients at 11% compared to the reported rate of 2%-4%. At diagnosis, there was an increased rate of renal failure in the young cohort compared to patients aged 41-65 years at 25% versus 16% and Bence Jones proteinuria at 81% versus 51%. The rate of complete or partial response was similar between the groups at 79% and 83% in the young and older cohorts, respectively. Median PFS post-ASCT was 22.0 months (95% confidence interval [CI]: 16.1, 28.0), versus 26.9 months (95% CI: 24.0, 29.8) for patients aged 41-65 years (P = .66). Median OS from date of ASCT was also similar to those over 40 years: 68.1 months (95% CI: 39.0, 97.2) versus 80.7 months (95% CI: 68.1, 93.4); P = .90. Treatment-related mortality (TRM) was low at 2.6% and 2.3% in the young and older cohorts, respectively. Despite previous reports that young age is a positive prognostic marker, our study found OS post-ASCT is equivalent to those aged 41-65 years. This study emphasizes the importance of developing strategies to better the outcomes of young patients with MM.