Pre Autologous Stem Cell Transplantation Research Articles

High Progression Free Survival Rates in Patients with Multiply Relapsed/Refractory Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant after Checkpoint Inhibitors: Results from Grupo Argentino De Trasplante De Medula Osea y Terapia Celular (GATMO-TC)

CONCLUSIONS Consolidation with autologous stem cell transplant (ASCT) in Hodgkin lymphoma (HL) was traditionally reserved for patients with chemosensitive disease. In 2021 a retrospective study showed encouraging results with ASCT consolidation after checkpoint inhibitors (CPI) in pts with relapsed/refractory (R/R) HL. Subsequently, several prospective studies with CPI +/- chemotherapy in 2nd line were published showing 1-year progression free survival (1-y PFS) rates of 90% but with increased incidence of engrafment syndrome. We aimed to evaluate survival outcomes of consolidation with ASCT after CPI in our cohort of patients with R/R HL and the incidence of engrafment syndrome. Patients with R/R HL who received consolidation with ASCT between 01/2016 and 5/2023 after treatment with CPI were included in this retrospective multicentric study. Descriptive statistics were used to summarize variables of interest. Progression free (PFS) and overall survival (OS) were estimated with Kaplan-Meier and variables were compared with log-rank test. Forty-one patients from 15 transplant centers in Argentina were analyzed. The median age at ASCT was 31 years (19-60). High risk features were present in three quarters of patients, 23 (56%) with primary refractory disease and 8 (19.5%) with early relapse. Eighteen patients (43.9%) had ≥3 of the 5 pre-ASCT modified AETHERA high-risk factors. Patients received a median of 4 (2-6) systemic therapies before ASCT, including 27 patients previously treated with Brentuximab Vedotin (BV) to which 26 were refractory. Thirty-six patients (87.8%) received CPI monotherapy and 5 (12.2%) in combination with chemotherapy. Thirty-six (87.8%) underwent ASCT after CPI and 5 received additional treatment before transplant due to lack of response or progression. Patients received a median of 7 cycles (2-34) of CPI before ASCT. Complete metabolic (CMR) and partial remission (PMR) pre ASCT was documented in 31 (75.6%) and 10 (24.4%) patients, respectively). The median time from last dose of a CPI to ASCT was 60 days (3-183). The most utilized conditioning regimens were BEAM (22%), BEC (22%), BeEAM (7.2%) and CBV (48.8%). Median time to neutrophil engrafment was 11 days (8-15). Engrafment syndrome was observed in 14 (34.1%) with 10 patients requiring treatment with corticosteroids. Seven patients (17.1%) received post ASCT consolidation with either CPI or BV. After a median post ASCT follow up of 12.3 months, only 2 patients relapsed and 3 patients died (one of progressive disease, one of transplant related mortality and the other of a late infectious complication). Estimated 1-y PFS was 92.6% for the whole cohort, 93.5% and 90% for patients undergoing ASCT in CMR and in PMR, respectively, p: 0.92 (Figure 1). Patients requiring additional treatment after CPI had an estimated 1-y PFS of 80% vs. 94.4% in those undergoing ASCT straight after CPI, p: 0.38. ASCT consolidation after CPI in this cohort of patients with high risk R/R HL was associated with very promising results even in those proceeding to ASCT in PMR. A third of the patients developed engrafment syndrome so it is important to be alert to the appearance of symptoms and evaluate early use of corticosteroids. Our findings are similar to the results of other studies and support ASCT consolidation in high-risk R/R HL patients receiving CPI.

Augmented ICE in Patients With Poor-Risk Refractory and Relapsed Lymphomas.

In patients with relapsed/refractory lymphoma after first line therapy, chemosensitivity to salvage chemotherapy is the main determinant of outcome pre-autologous stem cell transplant . With novel therapies not yet widely available and poor responses to conventional dose salvage therapy such as ifosfamide, carboplatin, and etoposide (ICE) in patients with early relapse within 12 months and primary refractory disease, there is capacity to dose intensify ifosfamide and etoposide (augmented ICE). We retrospectively evaluated patients who received augmented ICE between 2010 and 2020 and report on response, deliverability, toxicities, and outcome. Patients were transplant eligible with diffuse large-B cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) with refractory disease or relapse within 12 months. Dose of augmented ICE versus standard ICE was ifosfamide 10 versus 5 g/m2 and etoposide 600 versus 300 mg/m2. Carboplatin dose with a calculated area under curve of 5 was unchanged. Anti-CD20 monoclonal antibody was given in patients with CD20 positive lymphoma. Responding patients who achieved complete response or partial response proceeded to transplant. Twenty-one patients with DLBCL (n=13) and HL (n=8) received augmented ICE. Nineteen of 21 completed 2 cycles. Overall response rates were 85% (DLBCL) and 100% (HL). Most patients required transfusion, 2 developed reversible ifosfamide encephalopathy and 86% febrile neutropenia. Eighteen patients proceeded to transplant. 5-year overall survival (OS) and progression-free survival (PFS) in DLBCL were 62% and 45%, and in HL, 100% and 88%, respectively. Augmented ICE is associated with high response rate and transplant realization at the expense of toxicity.

Autologous Stem Cell Transplant in 2nd Line DLBCL in 2022, Still the Standard of Care ? a Monocentric Experience

Introduction: Patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) after frontline chemotherapy have a dismal prognosis. Salvage chemotherapy followed by high dose consolidation chemotherapy supported with autologous stem cell transplantation (ASCT) can achieve cure in about 50%, and remains the standard of care for fit patients under 70 yo. Nevertheless, this approach is less effective for patients with primo-refractory disease (refractory to 1st line CT or experiencing relapse during the 12 months after completion of 1st line treatment). With the advent of autologous CAR T cells targeting CD19 in second line of treatment, the place of ASCT must be redefined based on robust clinical data to offer candidate patients their best available treatment. As part of this "choose wisely" approach, we report the outcomes of patients receiving ASCT as consolidation therapy at our center. Methods: we report the retrospective experience of a monocentric transplantation program. Inclusion criteria were: 1) R/R DLBCL 2) In response to salvage therapy according to Deauville score criteria. Complete response (CR) was defined as Deauville scores 1-2-3, partial response (PR) as Deauville 4 or 5. 3) ASCT between 2010 and 2020 at IPC, Marseille 4) Conditioning regimen with BEAM or Bendamustine-Eam. The patients were stratified according to the NCCN-IPI in 2 groups: low risk (NCCN-IPI≤3) and high risk (NCCN-IPI>3). Univariate analyses included age, aaIPI, NCCN IPI and disease status pre ASCT. Multivariate analyse included disease status pre ASCT and NCCN-IPI Results: Ninety eight patients with a median age of 57 yo (26-71) were included. Most of them were primary refractory (52 patients, 53%). Patients received a median number of 2 lines of chemotherapy (2-4) before ASCT. At time of reinjection, all were in response (78% were in CR and 22% in PR). With a median follow up of 42 months (33-60), 3 year progression free survival (PFS) and overall survival (OS) were 68% and 82% respectively, and 3 year cumulative incidence of relapse (CIR) was 27%. In the whole group, 12 month NRM was 2%.Age was not associated with an increased risk of NRM (SHR 2.3 CI95 [0.44-12.24], p:0.3) . Three year PFS and OS were significantly higher in patients who underwent ASCT in CR: 3 years PFS 74% CR vs. 43% PR (HR 3.04 95CI [1.5-6.17], p: 0.001.), 3 year OS 88% CR vs 61% PR (HR 4.53 95CI [1.74-11.81 ], p< 0.001.). This was confirmed by multivariate analyse (HR 3.08 95CI [1.50,6.29] , p=0.0021 for PFS and HR 5.4 95CI [1.99-14.65 ], p=0.0009 for OS). Disease status at the time of ASCT and NCCN IPI >3 were strongly associated with PFS and OS (3 year PFS 71% CR and NCCN IPI ≤3 vs. 17% PR and NCCNIPI >3 (HR 5.62 95CI [2.03-15.54], p<.001 ) . Three year OS for CR and NCCN IPI ≤3 vs. PR and NCCNIPI >3 were: 86% vs. 17% (HR 16.15 95CI [4.87-53.57], p<.001). In the primary refractory group, 3 year PFS, OS and CIR were 70%, 75% and 22% respectively. No differences were observed with non primary refractory group (3 years PFS 66% vs. 70%, p=0.56 , 3 years OS 90% vs 75%, p= 0.077) Conclusion : We confirm that ASCT provides good disease control with few toxicity and remains a valid option in 2nd line DLBCL until 70 years of age. However, our results appear to be superior to previously published reports, even more in the group of primary refractory diseases, possibly due to a strict selection of patients achieving complete response after salvage therapy. Disease status before ASCT remains the most relevant parameter to predict survival, and should be incorporated in treatment decision algorithms to elect the optimal treatment sequence. Questions remain about the best strategy for patients in PR before ASCT, and we await long term results of randomized phase 3 CART cells studies (ZUMA7, TRANSFORM). According to our results, given the unfavorable prognosis of the group of patients in PR and NCCN IPI ≥ 3 could be the subgroup of patients that would most certainly benefit from CART cells. In conclusion, the best 2nd line strategy between ASCT and CAR T cells should be decided according to response quality, the access to CAR T cells program and economic impact. Moreover, the combination of pre treatment prognostic factors ( NCCN IPI) and pre-ASCT response to treatment could be even more halpful to choose the best consolidation treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

HL-300 Efficacy of Brentuximab Vedotin Plus Conventional Chemotherapy Regimens as Pre–Autologous Stem Cell Transplantation Re-Induction Salvage Therapy in Relapsed/Refractory Classical Hodgkin Lymphoma

Adding brentuximab vedotin (BV) to traditional chemotherapy protocols, followed by autologous stem cell transplantation (ASCT), has effected fundamental change in the treatment approach of relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). Several studies have shown a superior rate of complete remission (CR) up to 70%-87% in patients receiving BV-based salvage chemotherapy. Previous studies exposed pre-ASCT PET-CT negativity as the most important factor affecting the post-transplant outcome. Therefore, our objective was to evaluate the efficacy of BV-chemotherapy regimens by PET CT assessment of response rate. Single-center, descriptive retrospective analysis of 20 patients with R/R cHL, eligible for ASCT, treated at the University Clinic for Hematology - Skopje between January 2017 and January 2022. We reviewed demographic and clinical characteristics pointing to disease stage and the presence of unfavorable prognostic factors, treatment, and outcome. Patients received BV-chemotherapy combinations, including BV-DHAP and BV-ICE, or PET-adapted sequential chemotherapy with BV followed by augmented ICE. In patients receiving a BV combination, PET-CT was performed after 3 cycles. In patients treated with sequential chemotherapy who did not achieve response by 3 cycles of BV and received augmented ICE, PET-CT was performed after the second cycle. Fourteen patients (70%) had refractory disease and 6 patients (30%) had relapsed disease (3 with early relapse). The majority were male (70%). The mean age at the time of assessment was 39 (range: 15-63). According to the EORTC staging system, 14 patients (70%) were initially defined to have advanced stage. Patients had received 1-3 previous treatment lines. Seven patients with refractory disease received BV-DHAP. After 3 cycles, PET negativity was achieved in 4 patients (57.1%) and these patients proceeded to ASCT. All 5 patients with relapsed disease treated with BV-DHAP achieved CR. Two patients with refractory disease received BV-ICE and both of them progressed. Among 5 patients with refractory disease receiving sequential therapy, CR was confirmed in 3 (60%). One patient with early relapse received BV-augmented ICE and achieved CR. BV-based salvage chemotherapy is an effective treatment strategy for patients with R/R cHL, and it is reasonable to be moved forward as standard second-line therapy in R/R CD30+ cHL.

Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group.

Postconsolidation immunotherapy including dinutuximab, granulocyte-macrophage colony-stimulating factor, and interleukin-2 improved outcomes for patients with high-risk neuroblastoma enrolled on the randomized portion of Children's Oncology Group study ANBL0032. After random assignment ended, all patients were assigned to immunotherapy. Survival and toxicities were assessed. Patients with a pre-autologous stem cell transplant (ASCT) response (excluding bone marrow) of partial response or better were eligible. Demographics, stage, tumor biology, pre-ASCT response, and adverse events were summarized using descriptive statistics. Event-free survival (EFS) and overall survival (OS) from time of enrollment (up to day +200 from last ASCT) were evaluated. From 2009 to 2015, 1,183 patients were treated. Five-year EFS and OS for the entire cohort were 61.1 ± 1.9% and 71.9 ± 1.7%, respectively. For patients ≥ 18 months old at diagnosis with International Neuroblastoma Staging System stage 4 disease (n = 662) 5-year EFS and OS were 57.0 ± 2.4% and 70.9 ± 2.2%, respectively. EFS was superior for patients with complete response/very good partial response pre-ASCT compared with those with PR (5-year EFS: 64.2 ± 2.2% v 55.4 ± 3.2%, P = .0133); however, OS was not significantly different. Allergic reactions, capillary leak, fever, and hypotension were more frequent during interleukin-2-containing cycles than granulocyte-macrophage colony-stimulating factor-containing cycles (P < .0001). EFS was superior in patients with higher peak dinutuximab levels during cycle 1 (P = .034) and those with a high affinity FCGR3A genotype (P = .0418). Human antichimeric antibody status did not correlate with survival. Analysis of a cohort assigned to immunotherapy after cessation of random assignment on ANBL0032 confirmed previously described survival and toxicity outcomes. EFS was highest among patients with end-induction complete response/very good partial response. Among patients with available data, higher dinutuximab levels and FCGR3A genotype were associated with superior EFS. These may be predictive biomarkers for dinutuximab therapy.

A retrospective study of the association of pre-autologous stem cell transplantation disease status with outcomes in patients with multiple myeloma: A single-center study.

e20013 Background: Autologous stem cell transplantation (ASCT) has improved long-term survival for many patients with multiple myeloma (MM), but not all patients respond to ASCT favorably, and many experience disease relapse. Our goal was to explore various disease parameters in patients with MM that might be associated with adverse outcomes after receiving ASCT. Methods: We performed a retrospective medical record review of adult patients with MM who underwent ASCT at Henry Ford Hospital between January 1, 2010 and November 1, 2020. Age, sex, international staging system stage, type of induction therapy, bone marrow cytogenetics and/or fluorescence in situ hybridization, International Myeloma Working Group (IMWG) treatment response criteria categories before ASCT, and the use of maintenance therapy were collected. Outcomes analyzed were time to relapse (TTR) and overall survival (OS). Cox regression analysis was performed. Results: A total of 321 patient records were analyzed: 194 (60.4%) patients were &lt; 65 years old; 185 (57.6%) were men; 162 (50.5%) were Black, and 140 (43.6%) were White. IMWG treatment response categories before ASCT included 250 (78.2%) patients with partial response (PR) and very good partial response (VGPR) combined, and 40 (12.5%) with complete response (CR). There were 69 (21.4 %) patients classified with high-risk cytogenetics. Commonly used induction therapies included 96 (29.9%) patients receiving bortezomib/lenalidomide/dexamethasone, 21 patients (9%) receiving lenalidomide/dexamethasone, 80 patients (24.9%) receiving bortezomib/dexamethasone, and 30 patients (9.3%) receiving cyclophosphamide/bortezomib/dexamethasone, while other patients received a combination of other induction therapies. Mean time from ASCT and last follow-up date was 3.94 years. The overall mean TTR was 29.4 months and OS was 44.8 months. Univariate analysis showed that pre-ASCT treatment response status of combined PR/VGPR was associated with higher hazard of dying than CR (hazard ratio 3.03; 95% CI, 1.23-7.46); however, multivariate analysis showed that PR/VGPR status before ASCT was not significantly associated with increased TTR compared to CR (hazard ratio 1.29; CI, 0.65-2.59). Patients with pre ASCT CR status had longer OS than those with PR/VGPR status (hazard ratio 2.75; CI, 0.995-7.61; p &lt; 0.05). No other variables, including cytogenetic risk were associated with a difference in OS or TTR. Conclusions: Being at CR status before receiving ASCT may indicate a reduced risk of death in MM patients compared to PR and VGPR status, regardless of upfront therapies. Since multiple factors, including treatment type, impact CR status in patients with MM, we believe that studying evolving risk-adapted front-line therapies will help guide optimized treatment strategies to improve overall survival.

Daratumumab for post-ASCT maintenance treatment of myeloma.

Daratumumab, a potent CD38-directed monoclonal antibody, has veritably transformed the treatment landscape of multiple myeloma. 1 Nooka AK Kaufman JL Hofmeister CC et al. Daratumumab in multiple myeloma. Cancer. 2019; 125: 2364-2382 Crossref PubMed Scopus (58) Google Scholar CASSIOPEIA, a two-part, phase 3 trial, has brought daratumumab to the forefront of efforts aimed at improving outcome for transplant-eligible patients. 2 Moreau P Attal M Hulin C et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 29-38 Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar Part 1 randomly assigned 1085 patients with newly diagnosed multiple myeloma to receive four pre-autologous stem-cell transplantation (ASCT) induction and two post-transplant consolidation cycles of bortezomib, thalidomide, and dexamethasone (VTd) alone, or in combination with daratumumab (D-VTd). D-VTd showed considerable improvement in depth of response and progression-free survival, leading to its regulatory approval. 2 Moreau P Attal M Hulin C et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 29-38 Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar An improved overall survival with D-VTd became apparent with longer follow-up. 3 Moreau P Hulin C Perrot A et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021; (published online Sept 13.)https://doi.org/10.1016/S1470-2045(21)00428-9 Google Scholar A more contemporary regimen, D-VRd, involving lenalidomide, is awaiting mature data. 4 Voorhees PM Kaufman JL Laubach J et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136: 936-945 Crossref PubMed Scopus (169) Google Scholar Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trialDaratumumab maintenance every 8 weeks for 2 years significantly reduced the risk of disease progression or death compared with observation only. Longer follow-up and other ongoing studies will shed further light on the optimal daratumumab-containing post-ASCT maintenance treatment strategy. Full-Text PDF

Patients Responding to Any First Line Therapy for Multiple Myeloma Should Proceed to Autologous Stem Cell Transplantation Instead of Receiving Second Line Therapy to Deepen Response

Background: The current standard of care for transplant eligible patients with multiple myeloma, usually involves induction treatment with dexamethasone, a proteasome inhibitor and/or lenalidomide followed by autologous stem cell transplantation (ASCT). The optimal pre-transplant regimen and the extent to which we should try to deepen the pre-transplant remission remains undetermined. We therefore reviewed 496 patients with multiple myeloma who received ASCT at our institution with the goal of assessing predictors of outcome.Methods: 496 patient received 596 transplants between January 2005 and December 2015. The median age was 61 years (range 39 - 84), 58% were male and 26% had high risk features defined by cytogenetics, FISH and/or gene expression profiling (GEP). All patients received dexamethasone as part of initial myeloma therapy, 426 patients (86%) received a bortezomib-containing regimen, 347 patients (70%) received a lenalidomide-containing regimen, 302 patients (61%) received both bortezomib and lenalidomide, and 10 patients (2%) received a carfilzomib-containing regimen. A total of 25 patients did not receive lenalidomide, bortezomib or carfilzomib. The median time from diagnosis to transplantation was 7 months. The median follow-up time was 52.2 months (0.4 to 139.6). We analyzed the impact of the following on OS: age, disease type, stage and risk, pre-transplant dialysis, induction regimen, mobilization regimen, time to transplantation, transplantation regimen, CD34+ cell dose collected and administered, engraftment syndrome, response pre and post transplantation, and number of transplants.Results: We saw no difference in OS between patients receiving induction with lenalidomide, bortezomib or carfilzomib (either alone or in any combination) vs. no proteasome inhibitor or lenalidomide (p=0.4599). Having progressive disease at the time of transplantation predicted for a poorer OS (p=0.002) but all other responses (CR, VGPR, PR, SD) were not statistically different. These results apply to the entire cohort and individually for the low risk and high risk subsets. 11 patients had PD after first line therapy, of which only 1 was still in PD at the time of ASCT after receiving subsequent lines of therapy. However, of the 437 patients who were not in PD after first line therapy and continued treatment to deepen response, 29 patients evolved to PD at the time of transplantation. In multivariate analysis age > 60 (p=0.0059), high risk disease (p<0.0001), Mel 200 mg/m2 (p=0.0001) and PD response pre ASCT (p=0.0026) impacted OS.Conclusion: There was no impact on OS by the use of lenalidomide, bortezomib or carfilzomib pre-transplantation. Response depth prior to transplantation, with the exception of patients with PD, had no impact on OS. In our cohort, 7% of patients who were in CR, VGPR, PR or SD after first line therapy and received further lines of therapy to deepen response, evolved to PD prior ASCT. Since PD is determined to be a predictor of adverse outcome, our data supports continuing to second-line therapy only for patients in PD after first line. All other patients should proceed to mobilization and ASCT. [Display omitted] DisclosuresMcKiernan:Novartis: Speakers Bureau. Siegel:Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Skarbnik:Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Abbvie: Other: Ad board, Speakers Bureau. Biran:Takeda: Speakers Bureau; Celgene, Amgen: Consultancy, Speakers Bureau. Richter:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau. Pecora:Caladrius Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Goy:Genentech: Research Funding; Pharmacyclics / J&J: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Outcomes and toxicities in patients (pts) non-randomly assigned to immunotherapy Children’s Oncology Group (COG) ANBL0032.

10523 Background: Immunotherapy with the anti-GD2 antibody dinutuximab plus sargramostim (GM-CSF), aldesleukin (IL-2) and isotretinoin following consolidation therapy improved outcome for high-risk neuroblastoma (HRNBL) pts enrolled on COG ANBL0032. Randomization was halted in 2009; subsequent pts were non-randomly assigned to immunotherapy. Toxicities and survival were evaluated. Methods: HRNBL pts &lt; 31 years old with a pre-autologous stem cell transplant (ASCT) response of ≥ partial response (PR) were eligible. Demographics, INSS stage, tumor biology, 1993 INRC pre-ASCT response and toxicities were summarized using descriptive statistics. Five-year (yr) EFS and OS from time of study enrollment were estimated. Results: From 2009-2015, 1,183 pts were non-randomly assigned to immunotherapy. 96.7% (n = 1,144) were ≥18 months old and 83.1% (n = 765/921) had stage 4 disease. 45.1% (n = 363/805) of tumors with known biology were MYCN amplified, 94.5% (n = 749/793) had unfavorable histology, and 54.9% (n = 397/723) were diploid. Pre-ASCT, 352 (29.8%) pts had complete response (CR), 418 (35.3%) had very good partial response (VGPR), and 413 (34.9%) had PR. 1,042 (88.1%) pts underwent a single and 141 (11.9%) underwent tandem ASCT. For the entire cohort, 5-yr EFS was 61.1±1.9% and 5-yr OS was 71.9±1.7%. 5-yr EFS and OS for pts ≥18 months of age with stage 4 disease (n = 746) were 58.4±2.3% and 71.0±2.1%. 5-yr EFS and OS were 82.3±4.8% and 86.7±4.2% among pts with stage 3 disease (n = 110). EFS but not OS was superior for those with a CR/VGPR pre-ASCT vs. PR (5-yr EFS: 64.2±2.2% vs. 55.4±3.2%, p = 0.0133; OS: 72.7±2.1% vs. 70.5±2.9%, p = 0.3811). There was a trend toward improved OS for those treated with tandem vs. single transplant (5-yr EFS: 65.9±4.3% vs. 60.4±2.1%, p = 0.1282; OS: 76.5±3.8% vs. 71.2±1.9%, p = 0.0704). Grade ≥3 toxicities ( &gt; 10% of pts) during GM-CSF and IL-2-containing cycles, respectively, included pain (15.6/11.4%), fever (15.1/32.7%), anemia (18.9/21.7%), thrombocytopenia (13.9/17.4%), lymphopenia (12.3/16.0%), and hypokalemia (13.3/25.2%). Additional Grade ≥3 toxicities ( &gt; 10% of pts) included hypoxia (10.1%) during GM-CSF-containing cycles, and anaphylaxis (12.0%), neutropenia (16.1%), hyponatremia (16.5%), and hypotension (13.8%) during IL-2-containing cycles. Conclusions: In this large cohort of HRNBL pts treated with immunotherapy, 5-yr EFS was 61.1%. Superior EFS was observed for pts with stage 3 disease and for those with CR/VGPR pre-ASCT. IL-2-containing cycles were associated with increased toxicity. Clinical trial information: NCT00026312.

Evaluation of the Prognostic Value of Positron Emission Tomography-Computed Tomography (PET-CT) at Diagnosis and Follow-up in Transplant-Eligible Newly Diagnosed Multiple Myeloma (TE NDMM) Patients Treated in the Phase 3 Cassiopeia Study: Results of the Cassiopet Companion Study

Introduction: 18F-fluorodeoxyglucose positron emission tomography + computed tomography (FDG-PET/CT) is a reliable imaging technique for staging/monitoring in multiple myeloma (MM) with prognostic value for progression-free survival (PFS). The phase 3 CASSIOPEIA trial investigated the efficacy of CD38 mAb daratumumab + standard-of-care regimen bortezomib/thalidomide/dexamethasone (D-VTd) in TE NDMM patients (pts) vs VTd. In Part 1, D-VTd significantly reduced the risk of disease progression/death and improved stringent complete response (sCR), ≥CR, and minimal residual disease (MRD)-negativity rates vs VTd. Although MRD-negativity is associated with improved outcomes, relapse still occurs in MRD negative pts, potentially due to the presence of focal bone disease. The IFM 2009 trial showed pts with no residual disease assessed by MRD (multiparametric flow cytometry [MFC]) and PET/CT (double negative), achieved better PFS vs pts who were not double negative. Here, we report results of the CASSIOPET companion study of CASSIOPEIA, evaluating the prognostic value of PET/CT at diagnosis, post-consolidation PET-complete response (PET-CR) rates of D-VTd vs VTd, and concordance of PET-CR and MRD negativity. Methods: In Part 1 of CASSIOPEIA, 1085 TE NDMM pts were randomized to 4 cycles of pre-autologous stem cell transplant (ASCT) induction and 2 cycles of post-ASCT consolidation with D-VTd or VTd. Evaluations of MRD by 8-color MFC (10-5 sensitivity threshold) on bone marrow aspirates were performed and results were correlated with imaging data for the PET/MRD endpoint of CASSIOPET. The primary objective is to compare PFS in pts with MRD negativity and PET-CR post-consolidation vs pts who were not double negative, to be evaluated upon availability of mature PFS data. This analysis focuses on the prognostic value of PET/CT at diagnosis (PFS), post-consolidation double-negativity rates (MRD and PET), and concordance between MRD (MFC) and PET-CR negativity. Pts were excluded if they were randomized but not treated in CASSIOPEIA (n = 2). PET/CT scans were performed at baseline (prior to first dose) and post-consolidation (Day 100 post-ASCT). Acquired imaging data was uploaded to a central electronic repository system. Per Italian Myeloma criteria for PET Use (IMPeTUs) criteria, 5-point Deauville scores (range, 1-5) were applied to bone marrow (BM), focal lesions (FL), extramedullary disease (EMD), and paramedullary disease (PMD). For each PET dataset, localization of most intense FDG uptake was identified and maximum standardized uptake value (SUVmax) was calculated. CR = lesion uptake &amp;lt; mediastinum blood pool (MBP); unconfirmed CR (uCR) = lesion uptake between MBP and liver. An independent team of nuclear medicine physicians with extensive experience in MM interpreted the images, blinded to pt treatment. Results: A total of 268 (D-VTd, 137; VTd, 131) pts had assessable baseline PET prior to first dose and 184 (D-VTd, 101; VTd, 83) pts were PET evaluable post-consolidation (pts remaining on study with assessable PET at post-consolidation, baseline PET negative excluded). At baseline, 20.1% pts were PET negative and 79.9% pts were PET positive. 67.2% pts had FLs (91.7% with uptake &amp;gt;liver), with median SUVmax of 6.115 (range, 1.90-48.50). 22.0% pts had diffuse BM infiltration, and median BM SUVmax was 3.195 (range, 1.44-271.00). PET/CT showed PMD in 17.5% pts, with an PMD SUVmax of 7.110 (range, 1.91-39.80) and EMD in 7.8% of pts, with an EMD SUVmax of 6.850 (range, 3.86-21.14). Of 184 pts with post-consolidation PET measurements, 118 (64.1%) pts achieved CR, with 47 (25.5%) pts achieving uCR, 17 (9.2%) with partial response, and 2 (1.1%) pts with stable disease by PET. 12-mo and 18-mo PFS rates in PET-negative vs positive pts at baseline were 100.0% vs 92.5% and 100.0% vs 87.5%, respectively (Figure). In an assessment of post-consolidation concordance of PET-CR and MRD, 102 pts were MRD and PET-CT negative (Table 1). Post-consolidation double negativity rates of PET/CT and MRD were only 47.5% and 66.7% for VTd vs D-VTd (Table 2). Conclusions: In CASSIOPET, the PET/CT companion study of the CASSIOPEIA trial, we show that baseline PET-CT findings have prognostic value. More D-VTd pts reach double negativity of PET/CT and MRD post-consolidation vs VTd. With more mature data, PET-CR/MRD negativity concordance may provide insight into utilizing both methods as a predictive surrogate for pt outcomes. Disclosures Moreau: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Zweegman:Celgene: 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; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Perrot:Sanofi: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria. Facon:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Leleu:Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria. Belhadj:Amgen: Honoraria; Celgene: Honoraria, Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work; Takeda: Honoraria; Janssen: Honoraria. Karlin:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Levin:Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Educational Grant; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Educational Grant; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Educational Grant; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Educational grant ; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Educational grant . Minnema:Servier: Honoraria; Amgen: Honoraria; Celgene Corporation: Honoraria, Research Funding; Gilead: Honoraria; Jansen Cilag: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SkylineDx: Research Funding. Pei:Janssen: Employment, Equity Ownership. de Boer:Janssen: Employment, Equity Ownership. Vermeulen:Janssen R&amp;D, LLC: Employment, Equity Ownership. Kampfenkel:Janssen: Employment, Equity Ownership. OffLabel Disclosure: Bortezomib/thalidomide/dexamethasone (VTd) + autologous stem cell transplantation (ASCT) is standard of care in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. The phase 3 CASSIOPEIA trial evaluated the efficacy and safety of adding daratumumab to VTd (D-VTd) before and after ASCT. Although daratumumab is approved as monotherapy and in combination with standard-of-care regimens for the treatment of MM, D-VTd has not yet been approved. This presentation/paper includes information/discussion of D-VTd in the CASSIOPET companion study to CASSIOPEIA.

A Matching-adjusted Indirect Comparison (MAIC) of Bortezomib-Thalidomide-Dexamethasone (VTd) and Daratumumab Plus VTd (D-VTd) Versus Bortezomib-Cyclophosphamide- Dexamethasone (VCd) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) who are Transplant Eligible (TE)

In Part 1 of the phase 3 CASSIOPEIA study, pts with NDMM who were TE received D-VTd or VTd as pre-autologous stem cell transplant (ASCT) induction (four 28-day cycles) and post-ASCT consolidation therapy (two 28-day cycles). D-VTd improved rates of stringent complete response (sCR), minimal residual disease-negativity, and progression-free survival (PFS) compared with VTd. In Part 2 (ongoing), pts with a partial response or better were rerandomized to daratumumab maintenance or observation for 2 years.

A Matching-adjusted Indirect Comparison (MAIC) of Bortezomib-Thalidomide-Dexamethasone (VTd) and Daratumumab Plus VTd (D-VTd) Versus Bortezomib-Dexamethasone (Vd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) who are Transplant Eligible (TE)

In Part 1 of the phase 3 CASSIOPEIA study, patients (pts) received D-VTd or bortezomib-thalidomide-dexamethasone (VTd) as pre-autologous stem cell transplant (ASCT) induction (four 28-day cycles) and post-ASCT consolidation therapy (two 28-day cycles). D-VTd improved progression-free survival (PFS) and rates of stringent complete response (sCR) and minimal residual disease-negativity rate vs VTd. In Part 2 (ongoing), pts were re-randomized to D maintenance or observation for 2 years. In the phase 3 IFM 2005-01 study, pts received vincristine-doxorubicin-dexamethasone (VAd) induction (four 28-day cycles) with or without dexamethasone-cyclophosphamide-etoposide-cisplatin (dCEP) consolidation (two 28-day cycles), or Vd induction (four 21-day cycles) with or without dCEP consolidation therapy; all pts with a partial response or better post-ASCT were randomized (1:1) to receive lenalidomide maintenance or placebo until relapse.

A Matching-Adjusted Indirect Comparison (MAIC) of Daratumumab-Bortezomib-Thalidomide-Dexamethasone (D-VTd) Versus Bortezomib-Lenalidomide-Dexamethasone (VRd) in Patients (Pts) With Newly Diagnosed Multiple Myeloma (NDMM) who are Transplant Eligible

In Part 1 of the phase 3 CASSIOPEIA trial, patients (pts) received four 28-day pre-autologous stem cell transplant (ASCT) induction and two 28-day post-ASCT consolidation cycles of D-VTd or VTd. D-VTd improved progression-free survival (PFS) and rates of stringent complete response (sCR) and minimal residual disease (MRD) vs VTd alone. Overall survival (OS) remains immature. In Part 2 (ongoing), pts were re-randomized to daratumumab maintenance or observation for 2 yrs. In the phase 3 IFM2009 trial, all pts received three 21-day cycles VRd induction followed by either an additional 5 cycles of VRd or ASCT followed by 2 post-ASCT consolidation cycles of VRd (all pts then received 1 yr lenalidomide maintenance).

Prognostic Value of Pre-Autologous Stem Cell Transplantation PET/CT in Diffuse Large B-Cell Lymphoma: The Deauville Score Is Prognostically Superior to ΔSUVmax

Objective: The predictive value of pre-autologous stem cell transplantation (pre-ASCT) positron emission tomography/computed tomography (PET/CT) scans according to different criteria remains elusive in patients with diffuse large B-cell lymphoma (DLBCL). Methods: A total of 46 DLBCL patients treated with pre-ASCT were enrolled in the present study, and two methods, Deauville score and maximal standardized uptake value reduction (ΔSUV_max), were used to evaluate the PET/CT scans before transplantation. Results:In patients with Deauville 1–3 and ≥4, the 2-year progression-free survival (PFS) rates were 82.8 and 11.8% (p < 0.001), respectively, while the 2-year overall survival (OS) rates were 89.7 and 41.2%, respectively (p < 0.001). When using the ΔSUV_max cut-off of 66% criterion, in patients with a ΔSUV_max of >66 and ≤66%, the 2-year PFS rates were 78.1 and 7.1%, respectively (p < 0.001), while the 2-year OS rates were 87.5 and 35.7%, respectively (p < 0.001). In the univariate analysis, the ΔSUV_max, Deauville score, NCCN-IPI and serum lactate dehydrogenase levels were significantly correlated with the 2-year PFS/OS. Furthermore, the multivariate analysis revealed that the Deauville score was an independent prognostic factor for 2-year PFS. Conclusion: The present results indicate that PET/CT scans at pre-ASCT can predict the survival of DLBCL patients, and the Deauville score is better than ΔSUV_max in prognostic prediction.

S145 PHASE 3 RANDOMIZED STUDY OF DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D-VTD) VERSUS VTD IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PART 1 CASSIOPEIA RESULTS

Background: VTd is a standard of care for transplant-eligible newly diagnosed multiple myeloma (NDMM) patients. Daratumumab (DARA), a CD38 mAb, significantly reduced the risk of progression or death and improved complete response (CR) and minimal residual disease (MRD)-negative rates in relapsed refractory multiple myeloma or transplant-ineligible NDMM in phase 3 studies. Aims: We report the primary and final analysis of Part 1 of the CASSIOPEIA trial for NDMM. Methods: In Part 1, transplant-eligible NDMM patients 18–65 years old were randomized 1:1 to VTd (6 28-day cycles [C; 4 pre-autologous stem cell transplantation {ASCT} induction, 2 post-ASCT consolidation] of V 1.3 mg/m2 SC BIW Week [W] 1–2; T 100 mg PO QD; d 40–80 mg/week PO or IV W 1-4 C 1-2, W 1-3 C 3-6) ± DARA (16 mg/kg IV QW C 1-2, Q2W C 3-6). Melphalan 200 mg/m2 was pre-ASCT therapy. The primary endpoint was the rate of post-consolidation stringent complete response (sCR) assessed at Day 100 post-ASCT. Part 2 (maintenance) is ongoing. Results: A cohort of 1085 patients (D-VTd, 543; VTd, 542) was randomized. The Day 100 post-ASCT sCR rate was significantly higher for the D-VTd arm versus the VTd arm (28.9% vs 20.3%; P = 0.0010; Table). With 18.8-months median follow-up, progression-free survival (PFS) from first randomization favored D-VTd with a hazard ratio (HR) of 0.47 (95% CI, 0.33-0.67; P < 0.0001; Figure). With median PFS not reached in either arm, 18-month PFS rates were 92.7% versus 84.6% for D-VTd versus VTd. Rates of ≥CR, ≥VGPR, and MRD negativity supported sCR results (Table). Overall survival is immature with 46 deaths on study (D-VTd, 14; VTd, 32; HR, 0.43; 95% CI, 0.23–0.80). The most common (≥10%) grade 3/4 treatment-emergent adverse events (D-VTd/VTd) were neutropenia (27.6%/14.7%), lymphopenia (17.0%/9.7%), stomatitis (12.7%/16.4%), and thrombocytopenia (11.0%/7.4%). In the D-VTd arm, infusion-related reactions occurred in 35.4% of patients.Summary/Conclusion: D-VTd in induction prior to and consolidation after ASCT improved depth of response (sCR, ≥CR, and MRD negativity) and PFS with acceptable safety. The favorable benefit-risk profile supports the use of D-VTd in transplant-eligible NDMM. CASSIOPEIA is the first study to demonstrate the clinical benefit of daratumumab plus standard of care in transplant-eligible NDMM patients.

PB2324 LONG TERM OUTCOME OF AUTOLOGOUS STEM CELL TRANSPLANTATION IN ADULT ACUTE MYELOID LEUKEMIA PATIENTS: THE ROLE OF MINIMAL RESIDUAL DISEASE

Background:The role of autologous stem cell transplantation (ASCT) as consolidation therapy in acute myeloid leukemia (AML) remains unclear although most studies comparing ASCT with repeated cycles of intensive chemotherapy demonstrated a significantly lower rate of relapse following ASCT. Evaluation of minimal residual disease (MRD) can better identify patients who benefit from ASCT.Aims:We report our single center experience to evaluate long term outcome in terms of overall survival (OS) and disease free survival (DFS) of AML patients who consecutively received ASCT and to retrospectively analyze the correlation between MRD status pre ASCT and OS in patients with molecularly detectable MRD.Methods:From 1998 to 2018, 65 adult patients with de novo (61/65) or secondary (4/65) AML underwent ASCT at Seràgnoli Hematology Institute. Median age was 50 (range 16‐68 years). Most patients had favorable (23/65) or intermediate (35/65) cytogenetic‐molecular profile according to ELN2017 risk classification. 24 patients (MRD marker group) had any of the following detectable leukemia‐specific molecular markers at diagnosis evaluated through qPCR: 9 NPM1, 5 RUNX1/RUNX1T1, 10 CBFB/MYH11. All the patients received intensive induction chemotherapy: 24 patients received a “3+7” like induction therapy, 23 were treated with fludarabine‐based induction and 18 received a gemtuzumab ozogamicin‐containing regimen.Results:Sixty‐two out of 65 patients (95.4%) obtained complete remission (CR) after induction chemotherapy. In the MRD group, 13 obtained MRD negativity after induction, 2 after first and 8 after the second consolidation. The median number of consolidation cycles before ASCT was two. All patients received myeloablative busulphan based‐conditioning regimen in association to melphalan (74%) or cyclophosphamide (26%). 35 patients received bone marrow stem cells and 30 peripheral blood stem cells. Before ASCT five patients were MRD+ (2 NPM1, 3 CBFs). With a median follow up of 10 years, median OS of the population was not reached and median DFS was 2470 days. OS estimates at 3, 5 and 10 years were respectively 68%, 61% and 54%. Better outcome was observed in patients receiving more than one consolidation cycle in terms of DFS (p = 0.006) and OS (p = 0.03). MRD marker group patients had estimated OS at 3 and 5 years of 90% and 85% respectively. Of 30 patients who relapsed after ASCT, 16 received a rescue therapy and were successfully candidate to allogeneic stem cell transplantation (alloSCT) in second CR with a long survival rate of 50%. In the MRD marker group, 2/2 NPM1 MRD+ relapsed and 3/3 CBFs MRD+ (all with CBFB/MHY11 fusion transcript) obtained molecular remission and are still alive in CR. Pre‐ASCT MRD positivity do not impact prognosis in term of OS (10‐yr OS 80% for MRD+, 88% for MRD‐) or DFS (2‐yr DFS 70% and 61% for MRD‐ and MRD+ respectively). Of note, NPM1 MRD‐ patients who underwent ASCT remained in CR for a long time after ASCT (median OS not reached and median DFS of 1156 in NPM1‐ and 249 NPM1+).Summary/Conclusion:our study confirm that ASCT is a feasible and effective strategy for adult AML patients, mainly in those with low‐intermediate ELN2017 risk and treated with at least 2 post‐remissional cycles and it can concede long term survival mainly to NPM1 AML patients MRD‐ before ASCT. Relapse after ASCT can be successfully rescue by alloSCT. The application of prospective evaluation of MRD through more sensitive molecular methods (qPCR) on a wider population of adult AML patient may better select the patients who could benefit from ASCT.

BEAM Versus Single Agent High Dose Melphalan (HDM) Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplant (ASCT): A Retrospective Matched Analysis in Relapse/Refractory Hodgkin Lymphoma

Background The ideal conditioning regimen still remains a challenge in the autologous stem cell transplantation (ASCT) setting for relapsed/refractory Hodgkin Lymphoma (RR-HL). BEAM is the most popular preparative regimen but single agent high dose Melphalan (HDM) has also been used. However, the experience and data comparing BEAM vs. HDM are limited. Methods After the Institutional Review Board approval, we retrospectively evaluated the clinical course of 112 RR-HL patients, autografted from November 2008 till May 2017 in two different institutions. Twenty eight conditioned with HDM and compared in a matched paired analysis (1:3) with a cohort of 84 patients who received BEAM. The study groups had similar median age (30ys) and sex (M:F 1.7:1 vs. 1.8:1) and were matched for disease status before salvage (late relapse: 36 vs. 12, early relapse/primary refractory: 48 vs. 16 and disease status pre ASCT [complete remission (CR): 39 vs. 13 and partial remission (PR): 45 vs. 15]. BEAM regimen was given in the standard doses over 6 days, while HDM (200mg/m2) was given in a single day infusion. All patients received prophylaxis against microbial, fungal and viral infections; GCSF was routinely administered at the dose of 5mcg/kg at +1 day (BEAM group) and at +5 day (HDM group). The T-test and Kaplan-Meier method were used for the statistical analyses. Results The engraftment was successful; the median day for neutrophils >1000/mm3 was +11 for both groups while for platelets >20000/mm3 a faster recovery was noticed for HDM group: +13 vs. +22 days (p The 100 days non relapse mortality was acceptable for both groups: 2/84 (2.3%) in the BEAM group vs. 1/28 (3.5%) in the HDM group. Conclusion In this study, though retrospective, demonstrated that for RR-HL patients, the conditioning regimen consisting of HDM, offered at least comparable efficacy to the BEAM regimen. The earlier platelets recovery, and the shorter duration of chemotherapy administration (6 days for BEAM vs. 1 day for HDM), resulted in less hospitalization days, which along with the shorter period of GCSF administration post ASCT, may contribute to a better cost effectiveness for the HDM regimen. Nevertheless, prospective studies with larger series of patients and longer follow-up, including also a meticulous cost analysis, are warranted to determine the accurate role of single agent HDM as preparative regimen for ASCT in HL patients.

Prognostic Significance of Tracking Dynamic Changes in Positron Emission Tomography (PET) Scan Pre and Post Autologous Stem Cell Transplant (ASCT)

BACKGROUND:Multiple Myeloma (MM) is a heterogenous disease with variable outcomes based on both disease biology and burden. The revised international staging system (R-ISS) can distinguish 5-year overall survival (OS) however, it does not incorporate novel imaging that provide more accurate disease burden assessment (e.g., PET-CT). Previous studies (Usmani SZ et al Blood 2013) showed that the presence of more than 3 focal lesions (FL)s detected on PET-CT scan at baseline in newly diagnosed MM patients, or the persistence of any FL post induction therapy or post- autologous stem cell transplantation (ASCT), were associated with shorter progression free survival (PFS) and overall survival (OS) in Total Therapy trials. There is limited information available on the prognostic significance of PET-CT in the context of current standard 3-drug induction followed by ASCT in clinical practice. Herein, the investigators examined the prognostic implications of post-therapy PET-CT positivity in routine clinical practice.PATIENTS AND METHODS:The LCI MM database was interrogated (3/2014-5/2018) for NDMM patients who had undergone upfront ASCT and had PET-CT data available. Continuous variables were summarized with descriptive statistics, while categorical variables were summarized with frequencies and proportions. Survival distributions were estimated with Kaplan Meier techniques and compared using a log rank test PET-CT scan results were reported as negative or positive (defined as one FL having higher 18F-FDG uptake relative to uptake in mediastinum or surrounding background, with no similar activity seen on the contralateral side, or increased activity at any location incompatible with normal physiological distribution).RESULTS:A total of 198 MM patients were identified, 62 had pre-ASCT PET-CT scans and 80 patients had post-ASCT PET-CT. Median age at transplant was 62 years (range 25 - 77), 52.0% were female. R-ISS stage I (17.2%), stage II (41.4%), stage III (1.7%). The 3 years overall survival (OS) in patients with negative PET-CT post-ASCT vs. positive PET-CT post-ASCT was 96.6% vs. 74.2% (p-value 0.002) and median progression free survival (PFS) was 35 months vs. 13 months (p-value <0.001), respectively. Patients were then divided into three groups: Cohort 1- negative PET scan pre/post ASCT (n=35), cohort 2- positive PET-CT pre-ASCT/negative PET-CT post-ASCT(n=17), and cohort 3- positive PET-CT post-ASCT(n=6). Thirty-four patients had scans pre and post ASCT; an additional n = 24 had negative PET scans pre ASCT and did not require repeat PET scan post ASCT. At one-year landmark OS for cohort-1 was 100% vs cohort-2 100% vs cohort-3 66.7 (p-value 0.002). One-year PFS for cohort-1 92.5% vs. cohort-2 100% vs. cohort-3 66.7% (p-value 0.0513).CONCLUSIONS:Negative PET-CT imaging post ASCT is associated with better OS and PFS. Also, in our population, the absence of positive FL by PET-CT scan in newly diagnosed MM patients pre and post ASCT shows a trend towards better PFS and OS. Clearance of FL by PET scan trends towards improved PFS and OS. Longer follow up is needed to declare statistical significance between those cohorts. DisclosuresAtrash:Takeda Oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Voorhees:Amgen Inc.: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Novartis: Consultancy, Other: served on an IRC; TeneoBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy.

Infectious Complications in the Outpatient and Inpatient Autologous Stem Cell Transplantation Setting for Patients with Multiple Myeloma. Princess Margaret Cancer Center Experience

Background: Autologous stem cell transplant (ASCT) for multiple myeloma (MM) can be feasible and safe in the outpatient setting and has become standard of care at many centers. Limited literature, however, exists on the types of infectious complications, including specific pathogenic isolates and resistance patterns in the outpatient (OP) setting and whether these differ from the inpatient (IP) setting. This creates uncertainty and variation among local treatment guidelines on antibiotic prophylaxis and treatment of infections in the outpatient population.Methods:In this retrospective study, at total of 240 patients who underwent ASCT at our institution from 2015 to 2016 were reviewed. Study objectives included: 1) to describe the types of infections and pathogenic isolates in MM patients during the acute transplant period and 2) compare isolate results between patients undergoing OP vs IP ASCT. We also aimed to assess 30-day post-ASCT all-cause mortality, readmission rates, and incidence of multidrug resistant bacterial infections in each cohort. As per standard transplant protocol at our institution, all patients received ciprofloxacin and fluconazole prophylaxis and standardized initial therapy for febrile neutropenia with piperacillin-tazocin. Daily GCSF support was routinely used starting day +7 for IPs, and on demand only for OPs.Results:Patient, disease and transplant characteristics:Baseline demographics of both OP and IP cohorts are shown in Table 1 (total n=240; 109 OP, 131 IP). As expected, IPs had poorer performance status (KPS<90), more comorbidities (HCT-CI ≥3), more advanced stage MM, had worse pre-transplant renal function, and were more likely to receive Melphalan dose reductions. Median time to engraftment was similar between groups - 12 days for IP and 13 days for OP (range 9-25), with duration of neutropenia <0.5x10^9/L exceeding 7 days in 46% of the cohort. Median length of stay in hospital was 17 days (12-55) for the inpatients. In the OP cohort, 63.9% of patients required readmission to hospital, with median 3-day hospital stay. In total, only 4 (1.7%) patients required ICU admission.Infections in total cohort (OP and IP):Overall, 121 of 240 patients (50.4%) developed febrile neutropenia, with most common causes including: blood stream infection (BSI) (n=35, 29%), pneumonia (n=18, 14.8%) and respiratory virus infections (n=16, 13.2%). Opportunistic infections were uncommon (n=6, 2.5%) with 1 case of invasive aspergillosis and 5 cases of CMV infection.Of the 43 cases of BSI, 33 (76%) were identified as central line associated blood stream infections (CLABSI), 20 (46.5%) due to gram positive and 20 (46.5%) due to gram negative organisms. Multi-drug resistant gram negative organism isolates were observed in 22 patients (51%), including 5 cases of extended spectrum beta lactamase producing bacteria (ESBL; 11.6%), 9 cases of gram negative bacteria carrying inducible AmpC gene (SPICE; 20.1%), and 10 (23%) cases of quinolone resistant gram negative BSI.Comparison of IP vs OP infections:Although the OP cohort were less frail with fewer comorbidities than the IP cohort, they had more episodes of febrile neutropenia (64% vs 51%; p=0.042), worse mucositis (22.0% vs 10.8%, p= 0.021), and more BSI (24.7% vs 12.9% p=0.019). In the multivariable analysis, only OP status (OR 2.4, p=0.03) and baseline ANC<1.5 pre ASCT (OR 6.3, p=0.003) predicted for BSI occurrence.At 18 months, OS was 98.5% and PFS was 68% for all patients, with no difference between IP and OP (p=0.772). PFS was worse in patients with BSI (p=0.0031, HR 8.7), with gram positive infections in particular (p=0.0264, HR 4.9)Conclusions:In our autotransplant experience, blood stream and lung infections are common, with multi-drug resistance a concern. We were surprised to report that patients undergoing outpatient-based transplant had more BSI, presumably central line-related, and that this may impact disease outcomes (PFS). We hypothesize that outpatients may undergo additional line manipulation or inferior line hygiene, suggesting that enhanced patient/staff education on infection control measures should be a focus. In general, though, outpatient ASCT patients had excellent outcomes, with similar engraftment rates, short readmission rates, low ICU usage, as the entire cohort. DisclosuresTiedemann:Novartis: Consultancy; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Merck: Consultancy; Roche: Consultancy. Chen:Amgen: Honoraria.

Preliminary Analysis of the Australasian Leukaemia and Lymphoma Group (ALLG) MM17 Trial: Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone (KTd) for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy

BackgroundData from the Australian and New Zealand (ANZ) Myeloma and Related Diseases Registry (MRDR) shows that 85% of newly diagnosed multiple myeloma (NDMM) patients (pts) in ANZ are induced with bortezomib(V)-containing therapies, predominantly triplets of V-cyclophosphamide-dexamethasone (VCD). Of these, 15% demonstrate treatment failure - either a sub-optimal response (<partial response [PR]) (SOR) or primary refractoriness (1REF). Published data demonstrate that the outcome for these pts remains poor with short progression free (PFS) and overall survival (OS), thus representing an area of ongoing unmet medical need. The ALLG MM17 trial was designed to evaluate the efficacy of early response adaption with a switch to an intensive salvage strategy built around the triplet of carfilzomib-thalidomide-dexamethasone (KTd) in transplant eligible (TE) NDMM patients failing V-based induction.MethodsMM17 was a multi-centre single arm study sponsored by the ALLG. Eligible pts were TE NDMM undergoing pre-autologous stem cell transplant (ASCT) induction with V-based therapy and demonstrating either SOR (defined as <minimal response [MR] after 2 inductions cycles or <PR after 4 induction cycles) or 1REF (defined as disease progression while on or within 60 days of completing induction therapy). KTd was K56mg/m2 on D1, 2, 8, 9, 15 and 16 of each 28-day cycle (27mg/m2 D1 and 2 of cycle 1); thalidomide 100mg D1-28; and, dexamethasone 40mg on D1, 8, 15, and 22 of each cycle. VTE and anti-viral prophylaxis was as per individual institutional practice. Pts were planned to receive KTd x 4 cycles then undergo disease re-evaluation. Those achieving a stringent complete response (sCR) (defined as a morphologically normal bone marrow [BM] and immunofixation negativity and normalisation of the involved light chain isotype) proceeded to a MEL200 conditioned ASCT. Those with <sCR received a further KTd x 2 cycles, then proceeded to ASCT. Commencing at day 100 post-ASCT pts received a further 2 cycles of KTd and then continued Td to complete a total of 12 months post-ASCT consolidation. Euroflow minimal residual disease (MRD) evaluation was undertaken pre-ASCT, at day 100 post-ASCT, after KTd x 2 consolidation post ASCT and after completion of Td. CD138 enrichment of BM at study entry was assessed for EMC-92 gene signature for disease stratification utilising the Affymetric DX2 platform. Liquid biopsies at study entry were obtained to isolate cell free (cf) DNA for high-sensitivity targeted amplicon sequencing (TAS) for mutational characterisation of the MM at both study entry and relapse. The primary endpoint of the study was the overall response rate (ORR) to pre-ASCT KTd.ResultsFifty pts were recruited from 6 Australian sites between September 2016 and April 2018. EMC92 stratification was successful in 21 pts with 10 (48%) being high-risk and with cfDNA successfully obtained from 49 pts and currently undergoing baseline TAS. Data cut-off date was July 18 2018 with 39 pts evaluable for the primary end-point with the reverse-Kaplan-Meier estimate of the median potential follow-up for survival being 10.9 months (95% CI: 6.0 - 13.1 months). Median age was 50 years (36-71) with 72% males. Disease status at study entry was SOR in 26 (66%) (< MR n = 13, < PR n = 13) and 1REF in 13 (33%). The median number of pre-ASCT KTd cycles was 6 (6 cycles, n = 27 [69%]; 5 cycles, n = 1 [3%], 4 cycles, n = 5 [13%]; ≤ 3 cycles, n = 6 [15%]). Two pts were withdrawn due to treatment related toxicity - pulmonary arterial hypertension (n=1) and acute renal failure (n=1). One pt died of sepsis on treatment and one was withdrawn and subsequently died due to a second primary malignancy. ORR was 72% (95% CI: 56-83%)* - sCR 13%, CR 5%, VGPR 36% and PR 18%. Euroflow confirmed MRD negativity in 36% (14 of 39) of pts pre-ASCT and in 43% (12 of 28) at day 100 post-ASCT. Eight pts have progressed, 7 with highly aggressive extra-medullary disease. Neither median PFS (left panel) nor OS (right panel) have been reached.ConclusionsThis preliminary analysis of the ALLG MM17 trial demonstrates that early response adaptive escalation to KTd results in high response rates, including MRD negativity, in patients failing V-based induction therapy.*95% Credible interval from the posterior distribution. Bayesian updating based on observed data and a minimally informative prior for ORR with a median of 35%. [Display omitted] DisclosuresSpencer:Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. Quach:Sanofi Genzyme: Research Funding; Janssen Cilag: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Kalff:Janssen: Honoraria; Amgen: Other: travel to preceptorship; Celgene: Honoraria; Takeda: Honoraria. Bergin:AMGEN: Other: Travel to education meeting; Celgene: Consultancy. Reynolds:Novartis: Equity Ownership, Other: former employee of Novartis AG and holds stock in the company. .