Eligibility For Autologous Stem Cell Transplantation Research Articles

Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant

We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10−5 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT® system and liquid chromatography–mass spectrometry (LC–MS). Forty-two patients entered the treatment phase; forty were evaluable for the primary endpoint. The rate of sCR and/or MRD < 10−5 following C8 was 30/40 (75%), meeting the statistical threshold for efficacy. The 10−6 MRD negative rate improved with treatment beyond C8. Agreement between EXENT® and NGS was high and increased over time; agreement between LC-MS and NGS was lower. The estimated 3-year progression-free survival progression-free survival was 85%, and 3-year overall survival was 95%. Upper respiratory infections occurred in 67% (7% grade 3–4). There were no treatment-related deaths. Extended frontline Dara-KRd induced a high rate of sCR and/or MRD negativity; the rate and depth of MRD negativity improved beyond C8.

A 5-Stage System for ASCT Multiple Myeloma

652. Multiple Myeloma: Clinical and Epidemiological INTRODUCTION: In the last three decades, significant advancements in multiple myeloma (MM) treatment, including immunomodulators, targeted therapies, chemotherapy combinations, autologous stem cell transplantation (ASCT), and CAR-T therapy, have emerged. ASCT offers hope for MM patients by using high-dose chemotherapy with stem cell support. However, it carries risks of severe toxicity. Despite evaluating factors like age, performance status, and co-morbidities for ASCT eligibility, outcomes for MM patients still vary greatly. Various models, such as the ISS-series systems, have been developed to assess risk factors for progression-free and overall survival We conducted a study on 5,259 ASCT patients since 1989, identifying 7 easy variables (ISS stage, diagnosis-transplant interval, ferritin, transferrin, LDH, age, and gender) and creating a 5-stage system. This system helps evaluate the risk of MM patients before ASCT. METHODS: In this retrospective study, data from 5,259 MM patients receiving ASCT (1989-2022) were collected (median follow-up: 57 months). We assessed 30 clinical variables pre-ASCT. Multiple imputation was used to deal with the missing values. Patients were split into a 70% training set and a 30% validation set. Univariate/multivariate Cox regression analysis identified 7 clinical and demographic signatures. Signatures were scored based on hazard ratios normalized to ISS III vs. ISS I&amp;II. K-adaptive partitioning generated a 5-stage system, ATM5S, evenly distributed and validated in the training set. Harrel's c-index was used to compare ATM5S with the current myeloma systems. RESULTS: 3683 patients (70%) in the test cohort had a median age of 59.6, median PFS 38.8 month and median OS 56.1 month. IgG was the most common isotype (55%). Univariate Cox analysis showed that 27 variables were significant predictors for both PFS and OS. Multivariate Cox analysis showed that time from diagnosis to transplant, ferritin, transferrin, LDH, ISS stage, lymphocytes, platelets, calcium, gender and age were independent prognostic factors for both OS and PFS. We selected the most easy, understandable and well-distributed (with high-risk group&amp;gt;20%) 7 variables: ISS, time from diagnosis to transplant, ferritin, transferrin, LDH, age and gender and developed a score system, which resulted into a 5-stage system (ATM5S) by k-adaptive partitioning. This staging system also demonstrated a significant discriminatory effect in the validation set (30%, 1576 patients). CONCLUSIONS: The Arkansas Transplant-Myeloma 5-Stage System (ATM5S) showed a promising performance in both training and validation cohorts.

Eliminating Racial Disparities Among Transplant Patients in Multiple Myeloma after Referral to a Tertiary Center

Introduction: Autologous stem-cell transplantation (ASCT) remains an integral part of therapy for many newly diagnosed and relapsed multiple myeloma (MM) patients. Most tertiary centers rely on age, ECOG status, and multi-organ function evaluation to determine eligibility for ASCT. African Americans (AA) have a higher incidence of monoclonal gammopathy of undetermined significance (MGUS), higher incidence of MM and higher mortality rates than their Caucasian counterparts, mainly due to lower access to care. Furthermore, AA patients are also underrepresented in clinical trials. Studies have shown AA patients have similar to improved progression-free survival (PFS) and overall survival (OS) compared to Caucasian patients when similar therapies are offered to both groups; however, lower rates of transplantation are reported among AA patients. This is likely multifactorial in origin, with varying risk factors, biological influences, and social hindrances leading to racial disparity. We sought to examine the differences in rates of ASCT among African Americans vs Caucasian patients. Methods: We conducted a retrospective chart review of all patients with myeloma referred to our center between 2018 and 2022. Information regarding demographics, referral information, insurance and transplant status obtained for all patients referred and/or transplanted at our center were obtained from this chart review. The diagnosis date was obtained from referral records if they were referred from an outside institution. All patients received therapy at the discretion of treating physicians. Statistics are descriptive. Results: 206 AA patients were referred to our center for transplant evaluation, of which 138 underwent autologous transplantation (67%). Additionally, 141 Caucasian patients were referred to us for transplant evaluation, 98 of which underwent ASCT (69%). The transplant rates were similar across both genders among AA patients, with female AA patients accounting for 49% of all AA transplants. Among Caucasian patients, female patients accounted for 37% of all Caucasian transplants. The median referral delay time was 104 days among AA patients and 85 days among Caucasian patients. The median time from the date of referral to transplant was 128 days for AA patients and 124 days for Caucasian patients. The reasons for non-transplant varied between the two races. For African Americans, the most common reason was medical contraindication followed by patient disinterest in contrast to Caucasian patients, which was patient disinterest followed by medical contraindication. Conclusion: Once referred to a tertiary center, we observed no racial disparities among transplants in AA and Caucasian patients. While the median time from the date of referral to the date of transplant was similar across both groups, we noted an increased referral delay among AA patients.

Excellent PFS and OS of Newly Diagnosed Multiple Myeloma Patients Receiving Carfilzomib, Bendamustine, and Dexamethasone (KBD): A 6.5 Year Follow-up

INTRODUCTION While quadruplet regimens including PIs, IMiDs, and anti-CD38 mAb are now standard in the US for multiple myeloma (MM), the alkylating agent bendamustine has proven safe and effective in the first-line setting. 1 IMIDs can thus be preserved until relapse or replaced after adverse events. Carfilzomib has demonstrated efficacy in newly diagnosed MM. 2 We previously published the results of a phase I/II study of carfilzomib, bendamustine, and dexamethasone (KBD) in newly diagnosed MM during the pre-daratumumab era. 3 We report long-term survival outcomes. METHODS Patients enrolled in NCT02002598 with newly diagnosed MM and adequate renal function received IV carfilzomib, IV bendamustine, and IV/PO dexamethasone at prespecified doses for 8 cycles, each 28 days. 3 Stem cell collection for autologous stem cell transplant (ASCT) was performed after cycle 4. ASCT was performed after cycle 8 for transplant eligible patients. Maintenance was carfilzomib 36 mg/m 2 every 2 weeks or investigator's choice. Trial cessation occurred 12/2018. Here we provide an updated analysis of the outcome of patients with a median follow up of 77.5 months. RESULTS Data from 2/2014 to 7/2023 were reviewed. 19 patients received ≥2 cycles of KBD and were eligible for analysis. 5/19 (26.3%) had ≥1 high- or ultra-high-risk cytogenetic lesion (gain 1q, amplification 1q, 17p deletion/TP53 mutation, t(4;14), t(14;16), t(14;20)). 4 7/19 (36.8%) were R-ISS stage 1. 5/19 (26.2%) were R-ISS stage 3. ORR was 100.0% with 12/19 patients (63.2%) achieving a complete remission (CR) and 7/12 (58.3%) minimal residual disease (MRD) negativity. Median time to response was 1 cycle and to best response 7 cycles. 12/19 patients (63.2%) underwent ASCT. Times to neutrophil and platelet engraftment occurred in the expected timeframe. 16/19 patients completed median 19 maintenance cycles (IQR: 1-24). 10/19 patients (52.6%) received carfilzomib 36 mg/m 2 every 2 weeks; 5 patients received lenalidomide d1-21 every 28 days; 1 patient received KRd. 2 patients declined maintenance; 1 patient died prior to maintenance due to septic shock. After median follow up of 77.5 months (95% CI: 52.2-82.2), 7/19 (36.8%) patients suffered PD, including 3/12 (25.0%) who achieved CR. 1/19 died due to PD; 1/19 died due to septic shock. Median PFS was 77 months (34.5-NR); median time to next treatment (TTNT) was 77.0 months (36.1-NR). Median OS was not reached. 4/5 patients with high-risk cytogenetics suffered PD at median 48.6 months (14.6-NR); 1 without PD survived 17.2 months before loss to follow up. 1/5 high-risk cytogenetics patients died from PD at 37.2 months. For the 7/19 (36.8%) without ASCT, median PFS, TTNT, and OS were 41.8 months (9.8-NR), 45.2 months (9.8-NR), and not reached, respectively. 2/19 (10.5%) patients developed a second primary malignancy: melanoma in situ, fully resected; and localized prostate cancer at age 73, on active observation. No MDS occurred. CONCLUSIONS and DISCUSSION Patients with newly diagnosed MM who received KBD and, if eligible, ASCT had an excellent outcome with a median PFS of 77 months and a median OS that has not yet been reached at a median follow up of over 6 years. These findings equal or surpass the results achieved with RVD induction with a median PFS of 50 months for RVd + ASCT and 36 months for RVd only. 5 No adverse effects due to bendamustine were apparent, including development of MDS. KBD with anti-CD38 mAb should be explored as a viable IMID-sparing first-line regimen, regardless of ASCT eligibility. REFERENCES 1. Mateos MV, Oriol A, Rosinol L, et al: Bendamustine, bortezomib and prednisone for the treatment of patients with newly diagnosed multiple myeloma: results of a prospective phase 2 Spanish/PETHEMA trial. Haematologica 100:1096-102, 2015 2. Jasielec JK, Kubicki T, Raje N, et al: Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma. Blood 136:2513-2523, 2020 3. Leng S, Bhutani D, Raza S, et al: Phase I/II study of carfilzomib, bendamustine, and dexamethasone (CBD) in patients with newly diagnosed multiple myeloma. Blood Cancer J 10:13, 2020 4. Perrot A, Lauwers-Cances V, Tournay E, et al: Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma. J Clin Oncol 37:1657-1665, 2019 5. Attal M, Lauwers-Cances V, Hulin C, et al: Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med 376:1311-1320, 2017

Primary Endpoint Analysis from a Response Adaptive Phase II Clinical Trial of Carfilzomib, Lenalidomide, Dexamethasone Plus Daratumumab (KRd-Dara) in Patients with Newly Diagnosed Multiple Myeloma (NDMM)

Background Minimal residual disease (MRD) status has prognostic significance for progression-free survival (PFS) and overall survival (OS) in NDMM, but its value in guiding therapy remains unclear. We conducted a 2-stage, phase II trial evaluating the quadruplet regimen of KRd-Dara as induction therapy followed by MRD adapted KRd consolidation +/- autologous stem cell transplantation (ASCT) and maintenance versus observation. We previously reported the results of our stage I analysis at ASH 2022 (n=23; Blood 2022;140:4440-4441). Here we provide an updated analysis of the primary endpoint after completed enrollment of stage 2. Methods Eligible patients had NDMM with measurable disease. The induction phase allowed 8 cycles of KRd-Dara. Post-induction treatment assignment was informed by ASCT eligibility and MRD status by next generation sequencing (NGS at 10 -5), and included Group A (MRD negative, transplant-eligible and -ineligible, optional lenalidomide maintenance), Group B (MRD positive, transplant eligible, ASCT) and Group C (MRD positive, transplant ineligible, KRd consolidation for up to 12 cycles). Patients in Group B could receive up to 12 cycles of KRd consolidation therapy after ASCT if MRD positive. All groups could receive optional lenalidomide maintenance therapy after achievement of MRD negativity after induction ± consolidation. The primary endpoint was ≥complete response (CR) rate at the end of induction. The secondary endpoints were safety, MRD status, stem cell mobilization failure, and survival outcomes. Efficacy endpoints including MRD were evaluated with the intent to treat principle. Results Thirty-nine patients were enrolled: 23 in stage 1 and 16 in stage 2. Median age was 62 (range 34-78), 31% were female and 31% were African American. R-ISS stage 3 was present in 4 (10%), high-risk cytogenetics (including 1q21 gain) in 15 (39%). At the end of induction, ≥CR was achieved in 22/39 (56%, 90% CI: 42%-70%) patients including stringent CR (sCR) in 17 (44%), VGPR in 14 (36%) and PR in 1(3%). Of note, 2 patients did not complete induction therapy; one died during cycle 2, while another was withdrawn from study after an SAE during cycle 1. Evaluating by NGS, 62% achieved MRD negativity at 10 -5 and 41% MRD negativity at 10 -6 post-induction. MRD negativity by next generation flow cytometry (NGF) was 74% at 10 -5 and 31% at 10 -6. Concordance of MRD by NGS/ NGF at 10 -5 was 26/34 (76% in agreement and 24% disagreement, Cohen's kappa: 0.436), and by NGS/ NGF at 10 -6 was 17/25 (68% in agreement and 32% disagreement, Cohen's kappa: 0.351). 39 patients (100%) experienced treatment emergent AE, with grade ≥ 3 AE in 31 (80%). The most common (≥ 25%) any grade treatment related AE (TRAE) were diarrhea (39%), fatigue (36%), neutropenia (28%), and constipation (26%). Grade 3-4 TRAE (≥10% of patients) included neutropenia (21%) and hypophosphatemia (13%). Covid infection occurred in 10 (26%); only one patient needed hospitalization. Other infections (any grade) were seen in 20 (51%) patients. Fourteen (36%) patients experienced at least one SAE, of which 8 patients had a treatment-related SAE, including one death. Thromboembolic events were observed in 3 (8%) patients. Of 23 patients who collected stem cells upon completion of induction (7-8 cycles of KRD-Dara), 7 (30%) failed to collect an optimal target (3 million CD34+ cells/kg) on first attempt. Comparatively, 0 of 11 patients who collected after 3-5 cycles experienced stem cell collection failure (Fisher's exact: p=0.07). Post-induction, 24 patients were assigned to Group A, 8 to Group B, and 5 to Group C. After a median follow up of 26 months (95% CI: 17 - 27; data cut off 7/6/2023), 28 remain on treatment, 9 are in follow up, and 2 are off study. The 2-year PFS is 85.3% (95% CI: 71.6% - 99.1%); median PFS is not reached. Updated data on the best MRD/ CR/ sCR responses achieved post-induction will be presented at the meeting. Conclusions Our data confirm high rates of sCR and MRD negativity of the quadruplet regimen of KRd-Dara in NDMM. The safety data was in alignment with known safety profile of investigational products. With modification of the protocol to allow earlier stem cell collection, we were able to reduce the rate of stem cell mobilization failure from 30% to 0%. Based on our results, we recommend further testing of this MRD-based platform in randomized studies with stem cell collection after 3-4 cycles of KRd-Dara. Clinical trial: NCT04113018

Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis.

We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis. R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment. Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment. Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.

Outcomes of Older Adults with Non-Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation: A Mayo Clinic Cohort Analysis

Autologous stem cell transplantation (ASCT) is an important treatment that can offer a cure for patients with lymphoma. However, advanced age is an important factor that determines eligibility and outcomes after ASCT. Over the past decade, attributed to improved supportive care, ASCT for older patients has become more feasible. In this study, we report the single-center outcomes of older patients with lymphoma undergoing ASCT at Mayo Clinic Rochester to highlight its interval improvement over time and to help redefine the implications of ASCT in the chimeric antigen receptor T cell therapy era. This single-center retrospective study evaluated the characteristics and outcomes of older patients with lymphoma who underwent ASCT between 2000 and 2021. We report various relevant transplantation-related outcomes, including progression-free survival, overall survival (OS), relapse incidence, and nonrelapse mortality (NRM) in older patients with various lymphoma histologic subtypes. The main outcome was NRM, defined as the time from ASCT to non-lymphoma-related death, with relapse as a competing event. Of 492 patients age ≥65 years were analyzed. The median age at ASCT was 68.8 years. The most common indication for ASCT was diffuse large B cell lymphoma, accounting for 59.3% of cases. In multivariate analyses, patients undergoing ASCT in 2009 to 2021, an Eastern Cooperative Oncology Group Performance Status of 0, and low Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) (0 to 3) had a significantly lower NRM. Factors associated with OS included age, lactate dehydrogenase level, and HCT-CI. The 1-year NRM in older patients was low at 6.0%, in concordance with previous reports. Age should not be the sole factor determining a patient's ASCT eligibility. With the proper patient selection, ASCT remains a reasonable option for older patients with lymphoma.

Fixed Duration Daratumumab, Ixazomib, Lenalidomide, and Dexamethasone Quadruplet for Newly Diagnosed Multiple Myeloma - MRD Negativity and Survival Outcomes

Background: The combination of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and dexamethasone is the current standard induction therapy for myeloma. Daratumumab (Dara), a monoclonal antibody directed against CD38, is highly effective in treating myeloma and improves response rates and progression free survival (PFS) when added to a PI or IMiD. Recent studies have shown high efficacy rates with quadruplet regimens that contain these three drug classes, potentially allowing for limited duration therapy as well as reduction in the steroid doses. We designed this trial to examine the efficacy of the quadruplet regimen containing daratumumab, ixazomib (an oral proteasome inhibitor), lenalidomide and dexamethasone (Dara-IRd) given for fixed duration, and to evaluate impact of early discontinuation of steroids. Patients and Methods: Patients with previously untreated MM who had measurable disease and adequate organ function were enrolled, irrespective of their autologous stem cell transplant eligibility (NCT03012880). The primary objective was to determine the rate of complete response to Dara-IRD combination. Treatment involved 28-day cycles consisting of ixazomib 4 mg days 1, 8, 15; lenalidomide 25 mg days 1-21, dexamethasone 40 mg, weekly and Dara 16 mg/kg, weekly for two cycles, every other week during cycles 3-6 and then every 4 weeks thereafter during induction (12-cycles) followed by Dara-ixazomib maintenance (maximum 24 cycles). Patients were enrolled into two sequential cohorts: Cohorts A (n=38) and B (N=40), with dexamethasone discontinued after two cycles in Cohort B. Transplant eligible patients were allowed to collect stem cells for future transplant anytime after 4 cycles. Serum immunofixation was assessed with mass spectrometry (MASS-FIX) and marrow MRD negativity by Euro flow (sensitivity of 1 in 105). Results: Seventy-eight patients were enrolled; median age was 63.5 (range 33, 81), 55% were male. A third of the patients were high risk by mSMART criteria and ISS stage 1, 2, and 3 had 41%, 35%, and 24% of patients respectively. All patients have completed the treatment phase and those who have not gone off study continue on observation. Among the 40 patients who have gone off study, the reasons for discontinuation among patients in Cohorts A and B, respectively were: progression, 9 and 12; alternate therapy (most often transplant), 11 and 8. The best overall response on therapy was 96% including 31% CR, 39% VGPR. For the entire cohort, time to response was fast, median time to VGPR, CR or minimal residual disease negative (MRD) negativity was 4 cycles. Responses deepened over the duration of treatment as shown in the figure; 31% of patients achieved a marrow MRD negative status (28% CR and MRDneg). After a median follow up was 37.8 months, median PFS or OS has not been reached. Five patients enrolled on the study have died. A grade 3 or higher adverse event at least possibly attributed to the study drugs was seen in 56% of patients. The most common toxicities included fatigue, neutropenia, lymphopenia, peripheral neuropathy, diarrhea, and nausea. Stem cells were collected in 60 patients; median (range) of CD34 cells/kg 7.8 (2.8, 15.9) x 106, with plerixafor used in 88% of patients as per our standard of care "on-demand” approach based on blood CD34 count. Conclusion: Dara-IRd is an active regimen in newly diagnosed MM, with high overall rates of response and deep and durable responses with nearly a third of the patients being MRDneg (Mass Spec based blood testing and flow based MRD), that improved over time with therapy. The toxicities were manageable, with dose modifications. All patients were able to collect stem cells when required, though the majority needed plerixafor. This study demonstrates excellent outcomes with limited duration quadruplet regimen without planned upfront autologous stem cell transplant and no maintenance till progression. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Positron emission tomography derived metrics in relapsed or refractory large B-cell lymphoma with residual disease before autologous stem cell transplant.

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, maximum standardised uptake value (SUVmax ), total metabolic tumour volume (TMTV), and total lesion glycolysis (TLG) were calculated from the post-salvage/pre-ASCT PET scan. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 40% and 54% respectively. A D-5PS score of 5 (p=0.0082, hazard ratio [HR] 2.09), high SUVmax (p=0.0015, HR 2.48), TMTV (p=0.035, HR 1.83) and TLG (p=0.0036, HR 2.27) were associated with inferior PFS. A D-5PS score of 5 (p=0.030, HR 1.98) and high SUVmax (p=0.0025, HR 2.55) were associated with inferior OS. PET-derived parameters may help prognosticate outcomes after ASCT in patients with rrLBCL with residual disease after salvage chemotherapy.

Improving Outcomes for Patients with Multiple Myeloma through the Optimization of Treatment Sequences

Introduction: Multiple myeloma (MM) is an incurable disease characterized by the proliferation of malignant plasma cells within the bone marrow, causing a wide range of burdensome symptoms. Patients initiating treatment typically receive a combination of drugs across various classes with or without autologous stem cell transplantation (ASCT). However, patients will invariably relapse following initial treatment, and often require many lines of drug treatment over the course of their disease. Real-word data showed that a significant proportion of newly diagnosed MM patients that receive frontline (FL) treatment did not receive subsequent treatment. These high attrition rates suggest that using the best treatment upfront is crucial in delaying disease progression.The CASSIOPEIA (transplant-eligible [TE] setting), MAIA and ALCYONE (transplant-ineligible [TIE] setting) trials demonstrate that the addition of daratumumab (DARA) to standard of care treatments in FL significantly improves patient outcomes. Based on data from these trials, the European marketing authorization for DARA has been extended to the FL setting. To ensure the best possible long-term patient outcomes in clinical practice, the availability of new FL treatment options requires a redefinition of treatment patterns. Thus, we aim to investigate whether the adoption of DARA as a FL, as opposed to later-line, treatment of MM leads to better outcomes and improved clinical practice.Methods: In the absence of real-world sequencing data, we developed a clinical sequencing simulation using individual patient data from the DARA trials and indirect comparative evidence, across all indications in MM. We used progression-free survival curves to simulate health state transition probabilities across four lines of active treatment, to capture the efficacy of treatment sequences in MM. Patients start with initiation of FL treatment, and ASCT eligibility determines the sequences patients receive. Clinical expert opinion was sought to determine 1) the full range of meaningful treatment sequences and 2) which of these are used most in Italian clinical practice. Based on the clinical simulation outcomes, we calculated average time spent in each line of treatment, percentage of patients alive at different timepoints, and the total survival for patients initiating a sequence. This analysis included conservative attrition rates from trial data, 14% for TE (CASSIOPEIA) and 24% for TIE (MAIA/ALCYONE), assumed as similar across regimens in each setting.Results: In the TE setting, the best outcomes were achieved when using the DARA-based regimen (DVTd) as FL treatment, followed by either a LEN-based regimen (KRd) or a BOR-based regimen (PVd), resulting in a total survival of 14.2 and 14.1 years, respectively. In the TIE setting, the best outcomes were achieved when DRd or DVMP were used as FL treatment, followed by either a BOR-based regimen (PVd, for DRd) or a LEN-based regimen (KRd, for DVMP), resulting in a total survival of 11.7 and 10.9 years, respectively.In both the FL and second line (2L) settings, there was a clear survival benefit of using DARA. When comparing the DARA-based sequence with the current FL TE benchmark sequence (DVTd + KRd + Pd + Vd versus VTd + DRd + Kd + Pd), an additional survival of 1.5 years was observed in TE patients. When DARA was added to the current FL TIE benchmark sequence (DRd + PVd + Kd + Vd versus VMP + DRd + Kd + Pd), TIE patients lived on average 2.8 years longer. For TE patients, time spent progression-free ranged from an average of 4.83 to 7.99 years at FL, 1.42 to 5.40 years in 2L, 0.23 to 2.24 years in 3L and 0.17 to 1.53 years on 4L. For TIE patients, the variation was higher, leaving more room for optimization: 1.97 to 7.31 years at FL, 0.68 to 4.76 years in 2L, 0.17 to 3.25 years in 3L and 0.19 to 0.51 years in 4L.Conclusion: To our knowledge, this is the first sequencing simulation to consider optimal patient outcomes across several lines of MM treatment. The results show that the longest time in remission is achieved with the use of DARA-based regimens as FL treatment, significantly improving patient outcomes.Time spent progression free decreases with each subsequent line of treatment and the magnitude of the effect seen in the third and fourth treatment lines is not as significant as that of the effect seen in earlier treatment lines. Therefore, patients should be treated with the most effective treatment upfront. DisclosuresPetrucci: Celgene: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board. Mendes: Janssen-Cilag Farmacêutica: Current Employment. Boer: Janssen: Consultancy. Casamassima: Janssen: Current Employment. Willis: Janssen: Consultancy. Wadlund: Janssen: Current Employment. Matthijsse: Janssen: Consultancy. Armeni: Astrazeneca: Consultancy; Boehringer Ingelheim: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Johnson & Johnson: Consultancy; Amgen: Consultancy; Janssen: Consultancy.

P-117: Multiple Myeloma treatment patterns and outcomes in the public and private healthcare systems in Brazil: one country, two worlds

<h3>Background</h3> Over the past two decades, the approval of several novel drugs has broadened therapeutic options for multiple myeloma (MM) patients, but has also raised concerns about increasing drug expenses and healthcare costs in general. Access to these treatments in public and private settings in Brazil differs significantly and it is unknown if shortcomings in treatment availability affect patient outcomes. The aim was to understand the patient characteristics, treatment patterns and MM patient outcomes in private and public settings in Brazil. <h3>Methods</h3> MMyBrave is an observational, retrospective study with no control group. Eligible patients were diagnosed with active MM between January 1, 2008 and December 31, 2016 (cut-off date), at 17 public and private medical centers in Brazil. The MM diagnosis was performed according to investigator assessment. Data collection started on June 2018, after ethical approval, and progressed until August 2019. Demographic and clinical characteristics were collected. Patients were stratified according to eligibility to transplant (intention-to-treat analysis) and treatment setting (public or private health systems). The overall survival (OS) was analyzed using the Kaplan-Meier (KM) curve and Cox's proportional-hazards model. <h3>Results</h3> A total of 943 patients were included. Private and public centers accounted for 44.9 and 55.1% of patients, respectively. The age (≥65 years) and female percentage at private and public centers were 64.2 and 63.4%; and 43.6 and 48.6, respectively. The International Staging System stages I, II, III and stage unknown were: 26.7, 22.6, 25.7 and 25.0 at private centers and 13.3, 20.2, 27.4, 39.1 at public centers. A total of 47.9% (50.2% private and 46.1% public) were eligible for autologous stem cell transplantation (ASCT). Proteasome inhibitor (PI) regimens (mainly bortezomib-based) were used by 52.8% at private centers (57.3% in ASCT eligible; 48.3% in ASCT ineligible). MM patients in the private health system had a higher overall survival (OS) than those in the public setting (75.9 x 63.3 months, p=0,007). <h3>Conclusion</h3> Real-world MM patient outcomes at private and public institutions in Brazil were quite different, with significantly higher OS in those followed in the Brazilian private healthcare system. Disease staging and treatment response were found as independent OS predictors, regardless reimbursement setting and ASCT eligibility. These preliminary results raise the hypothesis that the superior OS among patients in the private healthcare system may be due to a wider availability of therapies.

Daratumumab, Ixazomib, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma

Daratumumab, Ixazomib, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma

Decision Making Factors That Influence Treatment Options for an Autologous Stem Cell Transplant for Older Adults (aged 65-75) with Newly Diagnosed Multiple Myeloma: A Mixed Methods Study

Background Multiple myeloma (MM) is an incurable hematological malignancy of older adults. Autologous stem cell transplant (ASCT) remains a standard of care with multiple retrospective and registry cohort studies demonstrating its efficacy in MM patients including older adults with the disease. Despite this favourable data, there remains wide heterogeneity in the utilization of ASCT, particularly among older adults with MM. We conducted a mixed methods study from the perspective of both oncologists and older adults with MM to: 1) identify decision making factors that influence ASCT eligibility and 2) to explore any barriers to ASCT utilization. Methods We conducted a mixed methods study at two academic centres and two community centres in Ontario, Canada. Older adults with MM (aged 65-75) who were within one year of treatment decision making regarding ASCT were invited to complete a survey from outpatient clinics. Oncologists (both community &amp; academic) were recruited via email. Semi-structured interviews were conducted with all participants who agreed to an interview. Thematic analysis was conducted to identify themes from the transcripts using NVivo (qualitative analytical software). The initial 3 transcripts were independently coded by two investigators, to develop a codebook. Any discrepancies were resolved using consensual validation. Once consensus was reached, the codes were then applied to the rest of the transcripts by one coder. A convergent parallel approach was used in combining the results of the qualitative and quantitative sections of the study. Results A total of 15 oncologists and 18 patients with MM completed the surveys. Baseline patient and oncologist characteristics are listed in Table 1. The majority of patients were offered an ASCT (78%) and among those offered, 79% went ahead with ASCT. Most patients were happy with the decision to either go ahead or refuse the transplant as indicated by a low decisional regret score (median of 5 and IQR of 0-19 out of 100, with a lower score indicating less regret with the decision). With regards to oncologists, 80% stated they were aware of geriatric tools to help with treatment risk stratification; however, the majority (75%) used none of these tools and relied on the 'eye-ball' test for decision making. Nine oncologists and 9 patients completed the semi-structured interview. Summarized themes identified are shown in Figure 1. From the perspective of patients, factors that most affected ASCT decision making were: strong trusting relationship with their oncologist (n=9), family support (n=9) and wanting the best treatment available (n=6). Top reasons to refuse ASCT were: fear of not recovering to baseline (n=2) and prolonged hospital stay (n=2). Oncologists identified using their clinical judgement (n=7), the belief that transplant was the best option (n=7) and lack of medical comorbidities (n=8), as the most important factors when recommending treatment. The lack of high quality randomized controlled trial data (n=9), local guidelines (n=5) and targeted assessment tools (n=7) were identified as barriers to ASCT. Notably, both patients (n=7) and oncologists (n=7) felt that ASCT decision making should not rely on chronological age alone. The findings of the qualitative and quantitative parts of the study concurred with each other and showed similar patterns. Conclusion To our knowledge, our study is the first to analyze contextual factors from the perspective of oncologists and older adults with MM that influence ASCT decision making and utilization. Despite guidelines supporting ASCT efficacy and safety among older adults with MM, our results demonstrate that the decision to undergo ASCT in older adults with MM is complex and variable both from the perspective of the patient and oncologist. Future incorporation of patient decision aids in parallel with enrollment of older adults in ASCT clinical studies and targeted geriatric assessments tools may provide an opportunity to enhance shared decision making and local guideline developments. Disclosures McCurdy: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Sanofi: Honoraria. Wildes:Carevive Systems: Consultancy; Janssen: Research Funding; Seattle Genetics: Consultancy. Mian:Sanofi: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy; Takeda: Consultancy, Honoraria.

Second Autologous Transplantation in Multiple Myeloma with Renal Dysfunction

Introduction Autologous stem cell transplant (ASCT) as a salvage option in patients (pts) with late relapse (≥18 months after upfront ASCT) represents an effective therapy and can prolong response in Multiple Myeloma (MM). Presence of comorbidities such as renal dysfunction can limit treatment options and impact ASCT eligibility. Efficacy and safety data supporting a second ASCT in pts with renal dysfunction for relapsed disease are limited. Methods All adult pts with MM with renal dysfunction undergoing a non-tandem second ASCT at our institution between January 2006 and January 2019 were identified. Renal dysfunction was defined as pre-transplant creatinine clearance ≤ 60 ml/min. Demographics, disease characteristics, and treatment history were compiled. Relapse free survival (RFS), overall survival (OS), relapse rate, and non-relapse mortality (NRM) outcomes were assessed. RFS durations after both the first and second ASCTs for each pt were compared using a paired log-rank test and corresponding hazard ratios (HR) was estimated using a paired cox proportional hazards regression model through mixed-effects models. Results Thirty six pts with renal dysfunction underwent a second ASCT at our institution. Fourteen pts (39%) had progressive disease (PD) and 9 pts (25%) had very good partial response or better. Median time between first and second ASCT was 57.05 months (18.98-103.25). Conditioning regimens included: ≤140 mg/m2 Melphalan (MEL) (61%; n=22), >140 mg/m2 MEL (28%; n=10) and BEAM (8.3%; n=3). Median length of hospitalization during second ASCT was 18 days (Range, 11-74). Median time to granulocyte and platelet engraftment was 12 (9-16) and 19 (0-61) days, respectively. In hospital events included: treatment-requiring infections in 15 pts (41.7%) and cardiac complications in 5 pts (13.9%). Four pts (11.1%) required intensive/critical care admission. By day 100 (d100) assessment, 30 of 34 surviving pts (83% by ITT) had stable disease or better, and 4 pts (11%) had PD. Twenty pts (58.8%) had an improvement in disease status compared to their pre-ASCT status, while 8 pts (23.5%) maintained their pre-ASCT disease status. Five pts (14%) were readmitted by d100, with 2 pts requiring intensive care. One of 2 pts on dialysis pre-second ASCT became dialysis independent. From second ASCT, median RFS was 1.04 yrs (95% CI, 0.74 to 1.67) and median OS was 3.34 yrs (95% CI, 3.30 to 7.99; median follow up 4.31 yrs); respectively. The cumulative incidence rates for relapse and NRM at 1 yr after second ASCT were 37.1% and 5.6%, respectively. By MVA, light chain MM was associated with higher relapse rate (p=0.03) and lower NRM (p=0.01). Conclusion Our data suggests that second ASCT is well tolerated with low complication /readmission rates in patients with renal dysfunction. Second ASCT as salvage can provide disease control for more than a year for these patients who may have limited treatment options.

Selecting transplant in the elderly: validation of IMWG frailty score and Revised Myeloma Comorbidity Index compared to clinical judgment

Autologous stem cell transplantation (ASCT) has proven safe and effective in selected elderly patients (pts) with Multiple Myeloma (MM); several comorbidities scores have been proposed but specific criteria for evaluating ASCT eligibility in elderly MM pts still need to be established. We performed an external validation of the IMWG frailty score and the revised Myeloma Comorbidity Index (R-MCI) in unselected elderly pts considered for ASCT at our center and treated according to clinical judgment.

Approach to the Older Adult With Multiple Myeloma.

Multiple myeloma (MM) is a disease of aging adults, and numerous therapeutic options are available for this growing demographic. MM treatment of older adults continues to evolve and includes novel combinations, new generations of targeted agents, immunotherapy, and increasing use of autologous stem cell transplantation (ASCT). Understanding age-related factors, independent of chronologic age itself, is an increasingly recognized factor in MM survivorship, especially in understudied populations, such as octogenarians. Octogenarians have inferior survival that cannot be explained by cytogenetic profiles alone. Incorporating assessments of geriatric factors can provide guidance on how to intensify or de-escalate therapeutic options. Functional status, using objective testing, is superior to traditional metrics of performance status and should be implemented to optimize the risk-benefit ratio of ASCT. ASCT is feasible and cost-effective, and chronologic age should not exclude ASCT eligibility. Upfront ASCT remains the standard of care, in the context of a sequential approach that includes pre-transplantation induction and post-transplantation maintenance. High-risk MM is classically defined by disease characteristics, yet shifting frameworks suggest that the high-risk designation could refer to any patient subgroup who is at risk for poorer outcomes-beyond disease-focused outcomes to patient-focused outcomes. Defining the optimal treatment of subgroups of older patients with high-risk disease on the basis of chromosomal abnormalities is unexplored. Here, we review tools to assess individual health status, explore vulnerability in octogenarians with MM, address ASCT decision-making, and examine high-risk MM to understand factors that contribute to survival disparities for older adults with MM.

Geriatric Assessment in Older Adults with Multiple Myeloma.

The incidence of myeloma in older adults is increasing, yet little is known about geriatric impairments in these patients. We aimed to examine the prevalence of geriatric impairments in older adults with myeloma and the association between geriatric assessment and autologous stem cell transplant eligibility. Prospective cohort study. Two academic medical centers. A total of 40 adults 65 years and older with newly diagnosed myeloma were enrolled. Participants completed a primarily self-administered geriatric assessment, including measures of functional status, comorbidities, polypharmacy, psychosocial status, social support, quality of life, cognition, and physical performance. Outcomes were autologous stem cell transplant eligibility and receipt. Forty patients enrolled; their mean age was 71 years. Geriatric impairments were common: 62% reported dependence in one or more instrumental activities of daily living (IADL), 76.9% had polypharmacy (four or more medications), and 47.5% had one or more comorbidities. Median time on the Timed Up and Go was 13.3 ± 4.9 seconds. Those considered candidates for autologous stem cell transplant (N = 26) were younger, with fewer comorbidities, better performance status, and faster performance on the Timed Up and Go test. Factors independently associated with receiving autologous stem cell transplant (N = 21) included age and IADL dependence. Impairments in geriatric domains are common in this population, even among those considered to have a good performance status. Geriatric assessment domains are associated with both transplant eligibility and receipt. J Am Geriatr Soc 67:987-991, 2019.

BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Prior to Autologous Stem Cell Transplant for Chemosensitive Relapses in Patients with Follicular Lymphoma: A Prospective Multicenter Phase II Study from Lymphoma Study Association (LYSA) Centers

Introduction: high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) is an effective treatment in relapsed follicular lymphoma (FL). Alternative regimens including bendamustine based conditioning (BeEAM) had been developed to improve lymphoma outcome. Visani et al. showed in a phase I/II for relapsed aggressive lymphomas and relapsed Hodgkin lymphomas that bendamustine used at a dose of 200mg/m2, 2 days in combination with cytarabine (400 mg/m2, day-5 to day-2), etoposide (200 mg/m2, day-5 to day-2) and melphalan (140 mg/m2, day-1) was well tolerated with promising efficacy results. We designed a single arm, multicenter, phase II study for first and second chemosensitive relapses in FL patients (pts) evaluating this conditioning regimen.Methods: The primary endpoint is the efficacy of BeEAM by measuring the 2-year event-free survival (2-year EFS) rate defines by relapse, progression, death from any cause and initiation of a new therapy. The hypothesis was the improvement of 2-year EFS rate from 70% (H0) to 85% (H1). Based on a Fleming-A'Hern single-stage design, 50 pts are needed. Secondary endpoints are: overall response rate (ORR) at day 100 according to 2007 Cheson criteria; progression-free survival (PFS); overall survival (OS) and safety profile of BeEAM. Main eligible criteria are: histologically confirmed FL relapsed (WHO grade 1, 2, 3a); aged 18-65 years; first or second chemosensitive relapses after salvage immunochemotherapy based on 2007 Cheson criteria with a complete (CR) or a partial response (PR) before the BeEAM; eligibility for ASCT; signed informed consent. This trial was funded by the French government PHRC program 2012.Results: Twenty-one pts were included between July 2014 and November 2016 in 7 LYSA centers. One patient did not receive the treatment. The final analysis was based on 20 pts. Inclusion were performed for 16 (80%) and 3 (15%) pts at 1st and 2nd relapses, respectively. One patient (5%) was included at 3rd relapse and is considered as protocol minor deviation. The median time between the initial diagnostic and the 1st relapse was 3.6 years (0.7-12.9). In first-line therapy, 17/20 pts (85%) were treated with immunochemotherapy. At the relapse allowing inclusion, the FLIPI score were 0-1, 2, ≥3 for 6 (32%), 7 (36%), 6 (32%) pts, respectively. Salvage treatments were rituximab (R) associated with, dexamethasone, cytarabine, and platin in 19 pts and R-CHOP in one patient. The median age at inclusion was 57 years (range, 39-63); 16 (80%) and 4 (20%) pts were in CR and PR before BeEAM. After 18 included pts, the protocol was amended due to unexpected toxicities especially two hepatic veino-occlusive diseases (VOD), leading to the reduction of bendamustine dosage. Finally, 17 and 3 pts were respectively treated at 200mg/m2, 2 days and 160mg/m2, 2 days. The median time for neutrophil>0.5 G/L and platelet recoveries>20 G/L were 7.5 (0-11) and 7 (2-18) days. Patients received a median of 4 (0-12) packed red blood cell units and 6 (3-21) platelet units until J100. The median duration of hospital stay duration was 27 days (20-50). Response evaluation at J100 showed 19 CR pts and one patient in progressive disease. The ORR was 95.0% (95%CI, 75.1-99.9). Six pts progressed with two deaths of the FL (Figure 1A). With a median follow-up of 31 months (16-42), the 2-year EFS rate was 59.6% (95%CI, 35.1-77.4) but two events correspond to unplanned rituximab maintenance in two CR pts (Figure 1B). The PFS and OS rates were 69.6% (95%CI, 44.5-85.1) and 90% (95%CI, 65.6-97.4), respectively (Figure 1C). Fifteen pts (75%) had infectious complications until J100 that needed treatments for more than 7 days. Grade ≥3 toxicities were infections (N=18, 90%), gastrointestinal disorders (N=14, 70%), mucositis (N=12, 60%); atrial flutter (N=1, 5%); acute renal failure (N=2, 10%); HHV6 reactivation (N=3, 15%). In total, 29 serious adverse events (SAE) were declared for 16 pts. Two pts experienced VOD classified as unexpected SAE; one of them needed a hepatic transplantation. No patient presented toxic death.Conclusions: the prospective evaluation of BeEAM conditioning in FL pts with a chemosensitive relapses showed excessive toxicities especially infectious complications, cases of VOD leading to premature termination of the trial. Based on the 20 treated pts, the outcome seems not improve with the use of BeEAM. Our study does not encourage the use of BeEAM conditioning in relapsed FL pts. DisclosuresGhesquieres:Sanofi: Consultancy; Gilead: Consultancy; Celgene: Consultancy. Le Bras:Amgen: Consultancy. Le Gouill:Roche: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria. Cartron:Celgene: Consultancy, Honoraria; Gilead Sciences: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Roche: Consultancy, Honoraria.

The IMWG Frailty Score and Age Can be More Effective Than Clinical Judgement in the Selection of Elderly Patients with Newly Diagnosed Multiple Myeloma Who Can Benefit from an Intensive Treatment Approach with High Dose Melphalan and Autologous Stem Cell Transplantation

The IMWG Frailty Score and Age Can be More Effective Than Clinical Judgement in the Selection of Elderly Patients with Newly Diagnosed Multiple Myeloma Who Can Benefit from an Intensive Treatment Approach with High Dose Melphalan and Autologous Stem Cell Transplantation

Safety of Autologous Stem Cell Transplantation in Patients with Known HTLV-1 Infection: A Case Series of 4 Patients

Human T-cell lymphotrophic virus types 1 and 2 (HTLV-1/2) are delta retroviruses endemic to the Caribbean and Japan (Gessain et al., 2013). They are known to cause adult T-cell lymphoma-leukemia (ATLL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (HAM) (Mahieux et al., 2003). Given the link between immunosuppressive states and development of lymphoproliferative disorders, there is hesitation on the behalf of clinicians to offer stem cell transplantation to patients who test positive for HTLV-1/2 antibody. We reviewed four cases of patients who underwent autologous stem cell transplantation (ASCT) at our institution after having tested positive for HTLV-1/2 antibody (Table 1). The median patient age at the time of ASCT was 58 years (range, 51-60). Two patients tested positive for HTLV-1 antibody and two tested positive for HTLV-2 antibody. Two patients underwent ASCT for treatment of multiple myeloma, one for diffuse large B-cell lymphoma (DLBCL), and one for light chain amyloidosis (AL). The myeloma patients received standard induction therapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) or lenalidomide, bortezomib, and dexamethasone (RVD). The DLBCL patient received rituximab, ifosfamide, carboplatin, and etoposide (R-ICE), while the AL patient underwent ASCT without induction. Three patients underwent conditioning with high-dose melphalan (200 mg/m2; HDM) and the lymphoma patient received carmustine, cyclophosphamide, and etoposide (BCV). Median stem cell collection was 8.35 x 106 CD34+ cells per kg (range, 4.8 -30.7). The median follow-up for these patients from date of transplantation was 22.4 months (range, 7.3-38.6). Median time to neutrophil and platelet engraftment was 9.5 days (range, 8-10) and 10 days (range, 9-14) respectively. Among these four patients, none developed complications related to HTLV-1/2 infection during the follow-up period. Two patients had a post-transplant course complicated by febrile neutropenia, and one patient developed typhlitis. One patient died on day + 221 due to a recurrence of cholangiocarcinoma leading to liver failure, and the other three remained alive at the time of last follow-up. Our data provides support that testing positive for HTLV-1/2 does not preclude eligibility for ASCT. DisclosuresSloan:Stemline Therapeutics: Consultancy.