Tandem Transplantation Research Articles

Cyclophosphamide Based Regimens Compared to Plerixafor-Based Regimens for Stem Cell Mobilization in Patients with Multiple Myeloma Result in Higher CD34+ Cell Yield, Lower Cost and Similar Outcome Post Autologous Transplantation

Background: Autologous stem cell transplantation (ASCT) is standard therapy for patients with multiple myeloma (MM). Stem cell mobilization for peripheral blood stem cell collection prior to ASCT is most commonly achieved with cyclophosphamide based chemotherapy regimens and GCSF (Cy-G) or with plerixafor and GCSF (Pler-G). Using a chemotherapy based mobilization regimen for patients with lymphoma has been shown to result in higher CD34+ cell yield and lower cost than plerixafor based regimens (Dhakal, et al. 2016). The question remains if stem cell mobilization regimens impact stem cell collection and ASCT outcomes in patients with MM.Methods: We reviewed 496 patients who received 596 ASCT for MM between January 2005 and December 2015. Data analyzed included stem cell mobilization regimen, number of CD34+ cells collected, number of apheresis procedures, CD34+ cells infused and survival. Univariate and Multivariate Cox Proportional Regression Models were utilized. The purpose of the review was to determine outcome differences between the use of Cy-G for stem cell mobilization vs Pler-G.Results: The median age at transplantation was 61 years (range 39-84) and 59% were male. Cy-G was used for stem cell mobilization for 438 patients (91%) vs 44 patients (9%) who received Pler-G. Significantly greater numbers of CD34+ cells were collected using Cy-G, with a median of 16.17 x 10e6/kg vs a median of 12.47 x 10e6/kg with Pler-G (p=0.0012). Median days of collection were less for Cy-G, 2 vs 3 for Pler-G (p=0.292), although not significant. There was no statistical difference in the dose of CD34+ cells infused, with a median of 5.73 x 10e6/kg for Cy-G vs a median of 5.00 x 10e6/kg for Pler-G. Pre-ASCT therapy using immunomodulatory agents lenalidomide, bortezomib or carfilzomib had no impact on the number of CD34+ cells collected (p=0.3427), number of apheresis procedures (p=0.6336) or CD34+ cell dose infused (p=0.941).OS at 84 months was 58% for patients using Cy-G for stem cell mobilization vs 55% for patients using Pler-G (p=0.9168) indicating no difference. By multivariate analysis, there was no difference in OS between the 2 groups (p=0.488). There was no difference in PFS between the 2 stem cell mobilization regimens by univariate or multivariate analysis (p=0.2737 and p=0.4226). There was no statistical difference (p=0.424) in the incidence of engraftment syndrome based on the stem cell mobilization regimen.Conclusion: For patients with MM, using a Cy-G regimen results in a higher CD34+ cell yield compared to Pler-G. Higher CD 34+ cell yield may be advantageous for patients considering tandem autologous transplantation. Pre-transplant therapy with immunomodulatory agents had no significant impact on CD34+ cell yield or apheresis days. There was no difference in OS or PFS between the 2 groups and no difference in the incidence of engraftment syndrome. The medication cost at our institution for a 70 kg patient receiving cyclophosphamide, dexamethasone and etoposide with GCSF is $8,846.64 compared to $24,846.09 for Pler-G. Cyclophosphamide based regimens for stem cell mobilization results in a higher cell yield with lower cost and equal survival compared to Pler-G in patients with MM. [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; Abbvie: Other: Ad board, Speakers Bureau; Gilead: Speakers Bureau. Biran:Celgene, Amgen: Consultancy, Speakers Bureau; Takeda: Speakers Bureau. Richter:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Janssen: Speakers Bureau; Takeda: 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. 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:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, 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; Genentech: Research Funding. Pereiras:Portola Pharmaceutical: Other: stock holder; TEVA: Consultancy.

Haplo-Identical Stem Cell Transplantation for Patients with Multiple Myeloma Who Relapsed after Autografting. a Study from the Cmwp of EBMT

IntroductionHaploidentical stem cells are becoming an alternative stem cell source for patients lacking an HLA-identical sibling or 10/10 HLA-matched donor. While an increasing number of studies for patients with acute leukemia, malignant lymphoma, and MDS are reported there are only very few results of haploidentical stem cell transplants in myeloma patients.Method and patientsIn EBMT registry 50 MMpatients with a median age of 55 y (r: 37 - 73) with relapse after autograft who received a mismatched related stem cell graft after myeloablative (n = 12, 25%) or reduced intensity conditioning (n = 37, 75%) between 2004 and 2014 were reported. The median time to relapse after single (n = 28, 56%) or tandem (n = 18, 36%) autologous stem cell transplantation was 6.2 months (r: 0.1 - 30.5) and the median time between last autograft and allograft was 17.4 months (r: 2 = 74 months).At time of allograft 4 (8%) of the patients were in CR, 21 (42%) in PR, 9 (18%) had stable disease or minor response, and 15 (30%) had progressive disease. The majority (84%) received peripheral blood stem cells as graft source and GvHD prophylaxis with ex- or in-vivo T-cell depletion (CD34 selection or ATG) (Cyclophosphamide post transplant) was performed in 37% of the patients while 63% did not receive any in-vivo or ex-vivo T-cell depletion.ResultsAfter a median follow-up of 52 months (95% CI: 12-112) the cumulative incidence of non-relapse mortality at 1 year was 20% (95% CI: 9 - 31%) and the cumulative incidence of relapse at 3 years was 56% (95% CI: 42 - 70%) resulting in an estimated 3-year PFS and OS of 15% (95% CI: 5 - 26%) 31% (95% CI: 7 - 45%), respectively. Significant factor for improved OS in a univariate analysis was only the use of BM (3 y OS: 71% (95% CI: 38 -100%) vs. 24% (95% CI: 11 - 38%), p = 0.02) and for relapse a higher but not significant incidence for ex-vivo T-cell depletion was observed (p = 0.07). The use of cyclophosphamide post transplantation as GvHD prophylaxis did not influence NRM, relapse incidence, PFS, OS, or chronic GvHD.ConclusionHaploidentical stem cell transplantation after relapse to an autograft is feasible for MMpatients. Major treatment failure is the high incidence of relapse. Post-transplant cyclophosphamide had no major impact on outcome in this limited number of patients. DisclosuresDreger:medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Jansen: Consultancy; medac: Other; medac: Other: Travel grants; medac: Other: Travel grants; medac: Other; Gilead: Consultancy, Speakers Bureau; medac: Other; medac: Other; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Jansen: Consultancy; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Gilead: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Riemser: Consultancy, Research Funding; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; Jansen: Consultancy; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; medac: Other: Travel grants; medac: Other: Travel grants; AbbVie: Consultancy, Other: Travel grants, Speakers Bureau. Corradini:Amgen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Gilead: Honoraria. Zuckerman:BioSight Ltd.: Consultancy. Ciceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Petersen:Sanofi: Membership on an entity's Board of Directors or advisory committees. Schönland:Sanofi: Research Funding; prothena: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Speakers Bureau. Garderet:Amgen: Honoraria; Takeda: Honoraria.

Prognostic Impact of Tandem Autologous Stem Cell Transplantation (ASCT) in Different Response Subgroups after 1st ASCT

Prognostic Impact of Tandem Autologous Stem Cell Transplantation (ASCT) in Different Response Subgroups after 1st ASCT

Bortezomib Consolidation after Nonmyeloablative Allogeneic Transplant Is Safe and Leads to a High Incidence of Immunophenotypic Complete Response in High-Risk or Young Myeloma Patients

▪Introduction: Allogeneic stem cell transplantation (alloSCT) is the only curative treatment for newly diagnosed multiple myeloma (NDMM) patients but is hampered by a high incidence of relapse and chronic graft-versus-host disease (cGVHD). We hypothesized that bortezomib (BTZ) in consolidation after tandem autologous stem cell transplantation (ASCT) and nonmyeloablative (NMA) alloSCT could decrease the incidence of cGVHD while improving quality of response.Method: NDMM patients ≤65 years with high-risk (HR) disease (defined as HR cytogenetics [del17p, t(4;14), t(14;16), t(14;20), del1p or gain 1q], ISS 3 or plasma cell leukemia) or ≤ 50 year regardless of risk status with an 8/8 HLA identical sibling or unrelated donor are eligible to participate in this prospective trial. After triplet BTZ-based induction chemotherapy and ASCT, outpatient NMA alloSCT is performed with either fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 for 5 days (sibling donor) or fludarabine 30 mg/m2 for 3 days and total body irradiation 2 Gy (unrelated donor) followed by peripheral blood stem cell infusion. Acute GVHD (aGVHD) prophylaxis consists of tacrolimus and mycophenolate mofetil (MMF). BTZ is started on day +120 post-transplant at 1.3 mg/m2 every 2 weeks for 1 year. Response evaluation is based on IMWG criteria. Bone marrow minimal residual disease (MRD) evaluation is performed with highly sensitive (≥10-5) next-generation flow cytometry using 8-color Euroflow protocol before alloSCT, before BTZ, every 3 months for 2 years and at relapse. Immunophenotypic complete response (iCR) is defined as stringent CR in addition to 2 consecutive negative MRD results. aGVHD and cGVHD are evaluated according to modified Glucksberg and NIH criteria, respectively.Results: As of 07/10/2017, 33 NDMM patients (16 males) have been enrolled; median age is 55 (range: 35-64) years. ISS 3 is found in 39%, Durie-Salmon stage 3A or 3B in 85%, HR cytogenetics in 58% (12% del17p, 15% t(4;14), 33% gain 1q21, 9% del1p and 12% with >1 HR cytogenetics). Induction consisted of CyBorD (79%) or VTD (21%) for a median of 4 (range: 4-7) cycles followed by ASCT. Median times from induction to ASCT and from ASCT to alloSCT are 5.7 and 4.4 months, respectively. Sibling donor transplants were performed in 42%. With a median follow-up of 15 months after alloSCT, 23 patients have started BTZ and received 96% of planned doses. No dose reduction was needed for toxicity. Consolidation BTZ improve depth of response, increasing ≥CR rate from 55% to 80% and iCR rate from 17% to 67% (Table 1), regardless of cytogenetic abnormalities. Median progression-free survival (PFS) is not reached; 12-month PFS is 87% (CI: 66-96) (Fig. 1). The cumulative incidence of progression at 12 months is 8%. Median overall survival (OS) is also not reached and 12-month OS is 91% (CI: 68-98). In 23 patients followed ≥6 months, cumulative incidences of grade II-IV and grade III-IV aGVHD are 30% and 15%, respectively. In 18 patients followed ≥12 months, the cumulative incidence of all grade and moderate-severe cGVHD at 12 months are 58% and 40%, respectively, with mostly mouth, skin and liver involvement. There is no clear association between time of occurrence of cGVHD and improvement of response. Three patients died, one from myeloma progression and 2 from grade III aGVHD, with a non-relapse mortality at 12 months of only 5%. Observed grade ≥3 non-hematologic toxicities possibly/related to BTZ include diarrhea (n=1), viral hemorrhagic cystitis (2 adenovirus, 1BK virus) and subclinical EBV reactivations (n=4).Conclusion: Tandem ASCT-NMA alloSCT and BTZ consolidation result in a remarkably high rate of CR or better including iCR. Despite a HR NDMM population, a low relapse rate is observed. BTZ following alloSCT is safe and may contribute to decrease both the incidence of cGVHD or its severity. [Display omitted] DisclosuresSebag:Celgene, Janssen: Consultancy. Cohen:University of Montreal: Patents & Royalties: royalties.

The Impact of Maintenance Therapy in the Treatment of Multiple Myeloma with a Subset Analysis on Patients Who Achieve a Complete Response (CR) or Better: A Retrospective Analysis

BackgroundMultiple myeloma (MM) is an incurable hematologic malignancy, which is now managed as a chronic disease. The general upfront treatment paradigm is induction therapy, followed by autologous stem cell transplant (ASCT) for those who are candidates, then maintenance for two years or until progression. The development of multiple novel drugs has extended median survival to over seven years. Patients who achieve a complete response (CR) or better following ASCT have improved outcomes. Likewise, minimal residual disease (MRD) negativity is associated with increased progression-free survival (PFS) and overall survival (OS), but its implications on practice patterns remain unclear. This raises the question of whether patients who achieve undetectable disease will benefit from maintenance therapy. Time off treatment may improve quality of life and decrease healthcare expenditure.MethodsA retrospective chart review was performed on all adult patients who underwent ASCT for MM at the University of Virginia between January 2012 and December 2016. Tandem or salvage transplants were excluded from the analysis. Data were collected on patient characteristics (age, sex), disease characteristics (immunoglobulin and light chain restriction, ISS stage, cytogenetic abnormalities), lines of systemic treatment prior to ASCT, depth of response achieved pre- and post-ASCT, and post-ASCT maintenance therapy. For patients who achieved CR or better post- ASCT, time to relapse, time to death, and duration of follow-up were collected. Patients with t(4;14), t(14;16), deletion 17p (or p53 deletion) were categorized as poor risk.Cox proportional hazard models were used to assess the relationship between the outcomes of interest and the different covariates of interest. In the univariate models, if the p -value was less than 0.1, then the covariate was considered in the final model. In the final model, covariates were removed if their p -values were greater than 0.1. For the final model, hazard ratios (HR) with confidence intervals (CI) are provided.ResultsSeventy-six patients were included in the analysis. Patient demographics and pre- and post-ASCT disease characteristics are described in Table 1. Median age at ASCT was 62 years. Sixty-three percent were male and 37% were female. Eighty-five percent of patients had poor-risk cytogenetics. Most patients proceeded to transplant after one (72%) or two (20%) lines of induction therapy. Thirteen percent achieved CR or better pre-ASCT versus 28% post-ASCT. Maintenance therapy was the only variable associated with time to relapse post-ASCT (p=0.005), as shown in Figure 1. Patients who did not receive post-ASCT maintenance were three times more likely to relapse (HR 3.0, 1.4-6.4 95% CI).Twenty-one patients (28%) achieved CR or better post-ASCT. Median follow-up was 27.5 months. Median time to relapse and death for these patients was 19.3 and 25.6 months, respectively. Thirteen patients received maintenance with bortezomib or lenalidomide, while seven were observed off maintenance. Data were unavailable for one patient. Four of the 13 patients on maintenance relapsed, while six of seven patients off maintenance relapsed. There was no significant difference in time to relapse between those who received maintenance and those who did not (p=0.91; HR 1.1, 0.3-4.1 95% CI).DiscussionMultiple myeloma is a chronic disease. New drug development and optimizing treatment combinations continue to extend time to next therapy and OS. Our findings of improved PFS with post-ASCT maintenance are consistent with prior large studies. The proportion of our patients who achieved CR or better post-ASCT is comparable to those in other prospective trials. Interestingly, maintenance did not seem to impact outcomes for our patients who achieved CR or better post-ASCT. Considering these findings, we question the additional benefit of maintenance therapy for patients with undetectable disease. It is possible these patients may remain off therapy for years and realize higher quality of life while sparing healthcare resources and expenditure. Our findings and conclusions are limited by the small population size and retrospective analysis. Larger, prospective studies are warranted. [Display omitted] DisclosuresFoster:Bristol Meyers-Squibb: Other: Clinical trial investigator.

The Effect and the Cost of Tandem Transplantation in Multiple Myeloma Patients with Adverse Cytogenetics

Introduction:Autologous stem cell transplantation (ASCT) plays a major role in the treatment of multiple myeloma. However, the result of STaMINA trial showed no extra benefit of second transplantation or consolidation therapy in addition to single ASCT; there is still argue about the optimal intensity of the treatment in patients with high-risk cytogenetic abnormalities. We analyzed retrospectively, the effect of the tandem ASCT and the cost.Methods:We analyzed multiple myeloma patients with Adverse Cytogenetics who were treated with ASCT in National Center for Global Health and Medicine Hospital from January 2010 to the end of March 2017. Most patients were treated with bortezomib based induction therapy. Patients who failed to achieve very good partial remission or better after the first ASCT proceeded to the second ASCT. Most patients received consolidation therapy and/or maintenance therapy. Overall Survival (OS) and progression free survival (PFS) was analyzed using the Kaplan-Meier methods, and the log-rank test. Also, cumulative cost for the treatment was evaluated. Adverse cytogenetics were defined as hypodiploidy, del(17p), t(4;14), and t(14;16).Results:Ten patients were treated with tandem ASCT, and fifteen patients were treated with single ASCT. Twenty-one patients were treated with BD regimen, two patients with CyBorD regimen, and two patients with VAD regimen. The median number of induction therapy was 4 cycles (4-6). The PFS of the tandem ASCT group (3yrs PFS was 87.5%) was superior to the single ASCT group (3yrs PFS was 37.2%) (P = 0.0038). The OS of the tandem ASCT group (3yrs PFS was 100%) was superior to the single ASCT group (3yrs OS was 49.5%) without statistical significance (P = 0.057). We compared cumulative costs of tandem ASCT patients with single ASCT patients. We plotted the average cumulative cost of every 3 months in each group. The first 21 months and beyond 54 months, the rate of cost increment was apparently higher in the single ASCT group than tandem ASCT group. A regression line was calculated for the average cumulative cost of single ASCT group and tandem ASCT group. Regression analysis revealed that overall inclination of the regression line of the cost in single ASCT was significantly larger than that of the cost in tandem ASCT (P = 0.0024).Conclusion:The outcome of tandem ASCT was superior to single ASCT in patients with adverse cytogenetics. Also, the total cost in patients with tandem ASCT was lower than that with single ASCT. Tandem ASCT may reduce the rate of relapse and the cost for salvage treatment. Therefore, tandem ASCT should be considered for multiple myeloma patients with adverse cytogenetics from a cost-benefit point of view. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hematopoietic, Immune Recovery and Outcomes after Autologous Stem Cell Transplantation Following Plerixafor Plus G-CSF Versus Chemotherapy and G-CSF Based Mobilization in Pediatric Patients

Background: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (ASCT) has shown survival benefits for chemo-sensitive high risk pediatric solid tumors. Collection of sufficient hematopoietic stem cells is required for ASCT. Plerixafor, a CXCR4 receptor antagonist, has been used when granulocyte colony-stimulating factor (G-CSF) and chemotherapy based (conventional) mobilization may not enable us to collect enough cells, especially in recurred or heavily treated patients. The experiences of plerixafor in pediatric patients are lacking as compared with adults, and immune reconstitution and outcomes in pediatric patients after ASCT with plerixafor based mobilization have not been reported in the literature as far as we have known. Therefore, we aimed to compare engraftment, hematopoietic and immune recovery and transplantation outcomes after ASCT between plerixafor plus G-CSF based and conventional mobilization group in pediatric patients.Methods: Propensity score matching (PSM) by optimal method with 1:1 ratio was performed to determine the control group. Age, sex, diagnosis, transplantation year, conditioning regimen, and number of transplantation were used as matching variables. We evaluated available parameters such as the day of neutrophil and platelet engraftment, absolute neutrophil counts (ANCs), absolute lymphocyte counts (ALCs), platelet and hemoglobin counts and lymphocyte subsets (CD3, CD4, CD8 [T cell] counts). Mann-Whitney U test was used to compare between two groups.Results: There were a total of 233 (21 plerixafor plus G-CSF based and 212 conventional mobilization group) patients who underwent HDC and ASCT in Seoul National University Children's Hospital between 2009 and 2016. By creating matched samples using PSM, 42 (21 plerixafor plus G-CSF based and 21 conventional mobilization group) patients were analyzed. The diagnoses were osteosarcoma in 14, brain tumor in 10, lymphoma in 6, neuroblastoma in 5, Ewing sarcoma in 4 and retinoblastoma in 3 patients. We used plerixafor plus G-CSF in patients who previously failed peripheral blood stem cell mobilization by chemotherapy and G-CSF. Patients received G-CSF (10 μg/kg) for 4 days, without prior chemotherapy. Then plerixafor (240 ug/kg) and G-CSF (10 ug/kg) were administered subcutaneously, at 10 and 2 hours before each apheresis. All 21 patients using plerixafor were mobilized successfully, and the median number of CD34+ cells were 10.65 (range 2.35-28.97) × 106/kg after 1 to 4 cycles of apheresis without serious complications. Fifty six ASCTs were performed, including 14 tandem transplantation. The median age at ASCT was 6 (range 3.7-22.4) years. All patients in conventional mobilization group achieved engraftment, but 2 patients in plerixafor plus G-CSF based mobilization group died due to acute respiratory distress syndrome before platelet engraftment and 1 patient died of sudden cardiac arrest before neutrophil and platelet engraftment. The engraftment tended to be faster in conventional mobilization group, but there was no statistically significant difference except for the day of ANC more than 0.5 × 109/L for 3 consecutive days (p=0.040). The ALC was lower in plerixafor plus G-CSF based mobilization group at one and six months after ASCT, respectively (p <0.001, p=0.041). The CD3, CD4 and CD8 count was lower in plerixafor plus G-CSF based mobilization group at one month after ASCT, respectively (p <0.001, p=0.007, p<0.001). The CD8 count was lower in plerixafor plus G-CSF based mobilization group (p=0.016), but the CD3 and CD4 count showed no statistical significant between-group differences at one year after ASCT, respectively (p=0.098, p=0.473). There was no significant between-group differences of overall survival (85.2% in plerixafor plus G-CSF based and 68.8% in conventional mobilization group, p=0.496) with a median follow-up duration of 22.7 (range 0.1-90.2) months.Conclusion: Hematopoietic and immune recovery tended to be slower in plerixafor plus G-CSF based mobilization group, but was done to a similar extent over time. In addition, transplant outcomes are similar between two groups. Our study suggests that plerixafor could be used safely and enabled more patients to procced to successful ASCT in pediatric patients. DisclosuresNo relevant conflicts of interest to declare.

Real World Outcomes of Newly Diagnosed High-Risk Multiple Myeloma Patients Treated at Princess Margaret Cancer Centre: A Retrospective Chart Review

Background: In the era prior to the availability of novel agents, we have previously reported that the median progression-free survival (PFS) and overall survival (OS) of high-risk (HR) multiple myeloma (MM) patients (pts) undergoing a single autologous stem cell transplant (ASCT) was only 9.9 and 18.3 months, respectively (Chang H et al., Bone Marrow Transplant, 36 (2005), 793). The current study expands our experience in newly diagnosed HR pts and focuses on the outcomes in pts treated with single or tandem ASCT.Methods: A retrospective chart review of myeloma pts was conducted based on pt information retrieved from the Princess Margaret Myeloma Database. 245 pts with HR MM diagnosed and treated in our centre from Oct 1998 to Dec 2016 were identified. Survival rates were calculated using the Kaplan-Meier product-limit method and the log rank-statistic was used for comparison of survival curves.Results: Pts were considered HR based on the presence of any one of the cytogenetic features: t(4:14) (71%), t(14:16) (36%), and chromosome 17p deletion (42%). Characteristics at the time of MM diagnosis of the 245 pts identified as HR are summarized in Table 1. The median age was 60.9 years. First-line therapy included the following: tandem ASCT in 86 pts (35%), single ASCT in 84 pts (34%), and no ASCT in 75 pts (31%). Of the 170 pts who underwent single or tandem ASCT, 119 (70%) received maintenance therapy post-ASCT, including 84% of the tandem ASCT pts and 56% of the single ASCT pts.Median follow-up was 29.3 months (range 1.1-123.7). The median PFS from date of diagnosis of all HR pts was 33.1 months [95% CI 29.3-37.0 months], while the median OS was 79.2 months [95% CI 58.3-90.9 months]. Both PFS (p= 0.0003) and OS (p= 0.0011) were significantly affected by first-line therapy with a median PFS of 53.1 vs 32.9 vs 21.8 months and median OS of 88.5 vs 71.9 vs 55.0 months in pts treated with tandem ASCT, single ASCT and no ASCT, respectively. Tandem ASCT pts had improved PFS and OS survival at 1, 2, and 5-years compared to single and non-transplant pts (Fig. 1A & B). Age at diagnosis significantly affected the PFS (p= 0.0003) and marginally affected the OS (p= 0.0748), likely due in part to our policy for the preferential use of fixed-duration non-ASCT as first-line therapy in older individuals (typically ≥70 years of age). On the other hand, serum beta 2- microglobulin levels correlated significantly with OS (p= 0.0023) while the association with PFS was not significant. Among ASCT pts, those who received tandem ASCTs vs single ASCT demonstrated a significantly better PFS (p= 0.0039) and showed a trend for improved OS (p= 0.0707). Amongst pts who received single ASCT, those with maintenance vs no maintenance demonstrated significantly better PFS (p=0.0082). Finally, pts with both t(4:14) and 17p deletion (28 pts) had a significantly decreased PFS (p= 0.0414) and a trend for decreased OS (p= 0.0621) compared to those with only one abnormality (Fig. 1C & D).Conclusions: Although adverse factors such as older age and co-morbidities likely affected the ability to perform 1 or 2 autografts and likely introduced bias into our analysis, our data nevertheless suggest that tandem ASCT is an effective approach in extending PFS and OS among HR MM pts when compared to single transplants or none at all in the real-world setting. Multivariate analysis is underway to further delineate the factors contributing to PFS and OS in HR pts. As in other transplant studies, the PFS is improved in pts who receive maintenance therapy after single ASCT. Efforts should be made to offer newly diagnosed HR MM pts a program that includes tandem transplantation, if feasible, as well as maintenance therapy post-transplant. Pts with “ultra HR” MM, i.e., those with both t(4;14) and 17p deletion, require new innovative approaches. [Display omitted] DisclosuresReece:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Paid expert testimony, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Paid expert testimony, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Otsuka: Research Funding. Chen:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbvie: Honoraria; Amgen: Honoraria. Kukreti:Celgene: Honoraria; Amgen: Honoraria. Prica:Janssen: Honoraria; Celgene: Honoraria. Tiedemann:BMS Canada: Honoraria; Celgene: Honoraria; Takeda Oncology: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Trudel:Janssen: Research Funding; Amgen: Consultancy, Honoraria; Astellas: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Honoraria; GlaxoSmithKline: Research Funding.

Tandem versus single autologous stem cell transplant: A patient-reported outcome.

e20026 Background: Whether tandem autologous stem cell transplant (ASCT) is superior to single ASCT for new diagnosed multiple myeloma (MM) patients remains a subject of discussion in the era of novel agents. This project analyzed patient-reported outcomes to single ASCT and tandem ASCT utilizing an online patient-centered platform. Methods: We analyzed patient-reported treatment outcomes pertaining to tandem ASCT and single ASCT from HealthTree Cure Hub ( www.healthtree.org ). In this study, we examined whether patients reported a reduction or no reduction in their myeloma after their tandem or single ASCT. The association between stem cell transplant and myeloma outcome was compared by chi-squared test. Results: In this retrospective analysis of 945 MM patients, we compared two groups, those that reported receiving a tandem ASCT (n = 75) and those that reported receiving a single ASCT (n = 870). Our analysis revealed an association between patients who reported receiving a tandem ASCT and a reduction of their myeloma (chi-square (1) = 3.87, p = .04), compared to patients who reported receiving a single ASCT. Conclusions: Tandem ASCT was perceived by patients to be superior over single ASCT in regard to myeloma reduction for the HealthTree patient population. A more in-depth analysis of the patient-provided health data from HealthTree could aid in determining factors related to survival as well as help to quickly answer lingering questions related to tandem ASCT, such as timing, genetic factors, progression free survival, and more.[Table: see text]

Improved outcomes with maintenance therapy after salvage autologous hematopoietic cell transplantation (AHCT) in multiple myeloma: A CIBMTR study.

8022 Background: Maintenance therapy in multiple myeloma (MM) after first autologous hematopoietic cell transplantation (AHCT1) is considered standard of care. Data regarding maintenance therapy after a salvage AHCT (AHCT2) in the setting of relapsed MM are scarce. Therefore, we used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to examine the use of maintenance therapy after AHCT2 in MM patients and its effect on post-transplant patient outcomes. Methods: We included US adult MM patients who underwent AHCT2 after melphalan conditioning regimen from 2010-2018, and excluded patients who underwent tandem transplants. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Cox proportional hazards models were developed to study the main effect (maintenance use) with other covariates of interest including age, sex, race, performance status, HCT-comorbidity index, MM subtype, stage, creatinine, cytogenetic, conditioning melphalan dose, disease status at transplant, and time from AHCT1 to AHCT2. Results: Of 522 patients, 342 received maintenance therapy and 180 did not after AHCT2. Baseline characteristics were similar between the two groups. Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Common maintenance regimens included immunomodulatory drugs (IMID)-lenalidomide (N = 145, 42%) or pomalidomide (N = 46, 13%) and proteasome inhibitor, bortezomib (N = 45, 13%). Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, p &lt; 0.001, REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)%, p 0.003, PFS 27.8% (22.4-33.5) vs. 9.8% (5.5-15.2), p &lt; 0.001, and OS 54% (47.5-60.5) vs 30.9% (23.2-39.2) p &lt; 0.001, respectively. IMID-containing maintenance regimens were associated with an improved 5-year PFS and OS compared to other maintenance regimens. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis, including NRM: hazard ratio (HR) 0.19 (0.08-0.44), p 0.0001, REL: HR 0.58 (0.47-0.72), p &lt; 0.0001, PFS HR 0.52 (0.43-0.64), p &lt; 0.0001, and OS HR 0.46 (0.36-0.60), p &lt; 0.0001. We conducted additional analyses to investigate a possible selection bias in the maintenance group including landmark analysis at 100-days and 6-months post-AHCT2 as well as a subgroup analysis of patients who received melphalan 200mg/m2 as conditioning for AHCT2 (as a surrogate for fitness)- all these analyses also showed improved outcomes in the maintenance group. Second cancers were reported in 17 (5%) patients in the maintenance group and 6 (3%) patients and no-maintenance group (p 0.39). Conclusions: Maintenance therapy after AHCT2 is associated with superior outcomes in MM patients.

Role of transplantation in treatment of multiple myeloma in era of novel agents

Multiple myeloma (MM) is a B-cell malignancy characterized by clonal proliferation of plasma cells. Despite the introduction of novel agents such as immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies, high-dose chemotherapy with autologous transplantation remains the primary treatment for patients with newly diagnosed multiple myeloma. This review presents the results of clinical trials assessing the effectiveness and safety of various kinds of transplantation such as single, allogeneic, tandem and salvage. Nowadays, in the era of access to new therapies, the following questions should be asked: when is the best time to perform autologous transplantation? What is the significance of allogeneic or tandem transplantation? Is the use of a second or third salvage transplant justified? Will chimeric antigen receptor T-cell (CAR-T) therapy become a valuable therapeutic method in MM? In this article, we will try to answer these questions.

Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

The role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

Current approaches to management of high-risk multiple myeloma.

The median overall survival in multiple myeloma is rapidly approaching 10 years; however, in nearly a fifth of patients the prognosis remains poor. Therefore, the modern-day management of myeloma patients should be individualized, with a more intense and continuous approach in these high-risk patients. This includes first-line treatment based on multi-drug combinations employing the most effective drug combinations, upfront autologous stem cell transplantation (in eligible patients with tandem transplantation being a consideration), and maintenance based on proteasome inhibitor-based combinations. This paper reviews the results of recent retrospective analyses and clinical trials, but also gives a glance into the future by presenting the ongoing trials.

Current Approach to Managing Patients with Newly Diagnosed High-Risk Multiple Myeloma.

With rapid advances in the therapeutic landscape and biological insights in multiple myeloma, it is critical to identify and strategically manage high-risk patients to achieve best outcomes with currently available drugs. The purpose of this review is to summarize the management of high-risk myeloma with a focus on recent advances in the field. The most widely accepted definition of "high-risk" is the Revised International Staging System (R-ISS) stage 3 disease, which includes high tumor burden (ISS stage 3) and high-risk FISH cytogenetics or an elevated lactate dehydrogenase level. A major advance in the management of high-risk patients is insight into the importance of achieving and sustaining minimal residual disease (MRD) negativity, which is an influential equalizer for long-term outcomes. Quadruplet pre-transplant induction regimens incorporating an anti-CD38 monoclonal antibody (mAb), proteasome inhibitor (PI: bortezomib or carfilzomib), lenalidomide, and dexamethasone should be strongly considered in high-risk patients given higher odds of getting to MRD negativity with these regimens compared to triplets. In transplant-eligible patients, upfront transplant does lead to a higher rate of sustained MRD negativity and superior PFS compared to delayed transplant. The role of tandem transplant in the context of bortezomib-lenalidomide-dexamethasone (VRD) induction therapy is unclear. Post-transplant maintenance therapy should include lenalidomide in combination with either bortezomib or carfilzomib until progression. For transplant-ineligible patients, VRD or daratumumab-lenalidomide-dexamethasone (DRD) until progressions are both reasonable and choice should be individualized based on patient-related factors. Outcomes of high-risk myeloma patients have improved in the last decade with the use of modern 3-drug induction regimens incorporating a PI and an immunomodulatory drug, with potential for further improvement as we bring anti-CD38 mAb upfront. MRD assessment will play a major role in treatment modification at several key time-points in the future such as pre-transplant, pre-maintenance, and yearly on maintenance therapy.

Pediatric high risk neuroblastoma with autologous stem cell transplant - 20 years of experience.

Background and ObjectiveNeuroblastoma is the most common extracranial solid tumor found in pediatric patients. High-risk neuroblastoma (HR-NBL) can be characterized by metastasis, age, and other tumor characteristics that result in an adverse outlook for this patient cohort. The standard of care includes induction chemotherapy, surgery, followed by stem cell autologous transplant (ASCT), and later, antidisialoganglioside (anti-GD2) antibodies. In this study, we provide the survival and toxicity data of our HR-NBL patients treated with a single ASCT.MethodsWe retrospectively analyzed pediatric HR-NBL patients treated with single ASCT after a carboplatin, etoposide, and melphalan (CEM) regimen in our institution between January 1993 and December 2014.ResultsThere were 99 evaluable patients with male predominance. The median age at diagnosis was 3 years. Most of our HR-NBL patients were stage 4 (88%). All patients received ASCT. Peripheral blood was the graft source in 58% of the patients. Time for hematological count recovery with bone marrow as a graft source was prolonged but not statistically significant when compared with PBSCs. Of all the patients, 58% received radiation therapy to residual disease. Overt secondary leukemia was not seen in any of these patients. Three-year overall survival (OS) was 68.5% ± 5.2% and the 3-year event-free survival (EFS) was (48.3% ± 5.2%).ConclusionOur HR-NBL patients tolerated high-dose chemotherapy well followed by single autologous stem cell transplant. Tandem transplant is a feasible option in our patient cohort. Apart from secondary solid tumors, there were no long-term complications seen.

47 - Tandem Transplantation in Myeloma Patients with High Risk Cytogenetics: A 10 Year Single-Centre Experience

47 - Tandem Transplantation in Myeloma Patients with High Risk Cytogenetics: A 10 Year Single-Centre Experience

258 - Tandem Autologous Hematopoietic Stem Cell Transplantation with Non-Cross Resistant Conditioning Regimens for Relapsed/Refractory Germ Cell Tumors: A Long Term Follow up of a Phase II Trial at the University of Minnesota

258 - Tandem Autologous Hematopoietic Stem Cell Transplantation with Non-Cross Resistant Conditioning Regimens for Relapsed/Refractory Germ Cell Tumors: A Long Term Follow up of a Phase II Trial at the University of Minnesota

248 - Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC): Tandem Transplant for Neuroblastoma Did Not Improve Overall Survival in Children Transplanted in Florida between 2010 and 2019

248 - Florida Pediatric Bone Marrow Transplant and Cell Therapy Consortium (FPBCC): Tandem Transplant for Neuroblastoma Did Not Improve Overall Survival in Children Transplanted in Florida between 2010 and 2019

Long-Term Follow-up of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Children and Young Adults with Metastatic or Relapsed Ewing Sarcoma: A Single-Institution Experience

Forty-seven patients with metastatic disease at diagnosis or recurrent Ewing sarcoma (EWS) received high-dose chemotherapy (HDC) followed by tandem (n=20, from February 13, 1997, to October 24, 2002) or single (n=27, from October 1, 2004, to September 5, 2018) autologous hematopoietic stem cell transplantation (ASCT). To our knowledge, this is the largest single-institution study with sustained long-term follow-up exceeding 10 years. All patients who underwent single ASCT received a novel conditioning regimen with busulfan, melphalan, and topotecan. The overall survival (OS) and disease-free survival (DFS) were 46% and 37% at 10 years and 42% and 37% at 15 years, respectively. Disease status at transplant and the time to disease relapse prior to ASCT were identified as important prognostic factors in OS, DFS, and risk of relapse. At 10 years, patients who underwent transplantation in first complete response (1CR) had an excellent outcome (OS 78%), patients in 1CR/second complete response (2CR)/first partial response (1PR) had an OS of 66%, and patients at third or more complete response, second or more partial response, or advanced disease had an OS of 26%. Ten-year OS for patients without a history of relapse, with late relapse (≥2 years from diagnosis), or with early relapse (<2 years from diagnosis) was 75%, 50%, and 18%, respectively. Selected patients in 1CR, 2CR, 1PR, and with late relapse had excellent, sustained 10- and 15-year OS and DFS.

Early Mortality Risk in Patients with Multiple Myeloma

BACKGROUND: Advances in treatment has improved greatly survival of multiple myeloma in the last two decades, and this improvement has been endorsed by wider use of novel drugs and tandem autologous stem cell transplantation. However, still there were cases died earlier post diagnosis OBJECTIVES: To study the risk factors of early mortality in patients with multiple myeloma In Kurdistan region of Iraq PATIENTS AND METHODS: A 176 cases that were diagnosed with symptomatic multiple myeloma between (January 2012 – July 2019) in cancer centers in Kurdistan region of Iraq. A total of 152 were continued within the study through their recorded sheet. Their data were analysed to determine what are the main risk factors that have an impact on early mortality among our myeloma patients. RESULTS: Among the total of 152 studied patients nine of them (5.9%) died early. The highest proportion (32.2%) of the sample aged 60-69 years, more than half (57.2%) of the them were male. The majority of the patients (80.9%) have been diagnosed during 2016-2019. The incidence of early death was 8.7% among patients who didn’t take the cytotoxic treatment compared with 1.7% of patients who took that treatment, but the difference was not significant (p = 0.089). The early death rate was significantly high (22.2%) among patients who didn’t take the immunomodulatory drugs, versus 2.4% of patients who took the immunomodulatory drugs (p = 0.001). The incidence of early mortality was 9.6% among patients with lactate dehydrogenase of ≥ 250 U/L compared with 0%