Cyclophosphamide, Etoposide, and Intermediate-Dose of Carboplatin; An Efficient Preparative Regimen for Autologous Transplantation for Patients with Lymphoma, a Good Alternative to Those Based on Carmustine. Experience with 108 Patients

Autologous Stem Cell Transplantation (ASCT); is a universal accepted therapy for rescuing relapsed Hodgkin (HL) and non-Hodgkin (NHL) lymphoma patients and for consolidation of mantle cell lymphoma (MCL). The most used preparative regimens in this setting are BEAM and CBV. both of them include carmustine, a medication with serious shortage and cost problems, therefore , is very important to find alternative regimens. During the nineties the combination of high dose of carboplatin plus cyclophosphamide and etoposide (CEC) was explored, however, it was abandoned due to high toxicity. We present our experience with 108 patients using this regimen but with intermediate dose of carboplatin (Inter CEC) Methods: We did a retrospective descriptive longitudinal observational study. All consecutive patients who met the inclusion criteria; age above 18 years, diagnosis of HL, NHL, M CL, and transplanted with Inter CEC were included. The preparative regimen consisted of carboplatin 900 mg/m2, etoposide 900 mg/m2, and cyclophosphamide 6.000 mg/m2, split in five days (fig 1). All patients received peripheral blood stem cells, and from d + 5 until neutrophil recovery, daily filgrastim. Every patient signed informed consent and the study was approved for institutional ethical committee. Results: From Oct 2013 to May 2020, 108 patients were included; median age was 45 years (18-70), 43.5% were female, 20% were older than 60 years and 79.6% had advanced disease at diagnosis. Thirty-five (32.4%) had HL, 35 (32.4 %) NHL (28 diffuse large B cell, 7 follicular), 29 (26,9%) had MCL, and 9 (8.3%) had other lymphomas. 34% of HL patients and 48% of cases were transplanted in CR1 after being refractory to first line therapy, while 44% and 14% of HL and NHL respectively had active disease at the time of transplantation. Regarding MCL cases; 21 (72,4%) had MIPI above 3 points and 96.5% were transplanted in first remission. All of the evaluable patients at day + 30 had hematopoietic recovery, median time to achieve 500 neutrophil /ul or more was 12.3 days (10-30) and for self-sustained platelet counts, 20.000/ul or more, was 15.3 (10-34). After a median follow up for surviving patients of 42,2 months the overall survival (OS) (Kaplan-Meier) at 48 months for the entire group was 74% (CI 63-82) and the event free survival (EFS) was 57% (CI 43-69). When the OS and EFS were discriminated for diseases, it was; for HL 76% (CI 56-88) and 43% (CI 17-66), for NHL 78% (CI: 57-90) and 68% (CI 42-83), and for MCL 69% (48-83) and 57% (CI 32-76) respectively (Fig 2). Eleven out of 18 patients (61%) transplanted with active disease achieved complete remission and 14 out of the entire group relapsed during the first years of transplant The transplant related mortality (TRM) at 1 year was 2.8%, the relapse associated deaths were 13% and, in 5 patients, who died after one year of transplant, the cause was not found. The main toxicity was mucositis; 46%, (grade II-IV: 22%), 30 patients (28%) had confirmed infections; bacteremia 17 cases, pneumonia 5, and others infections 6. Renal toxicity occurred in 24 cases (22%), grade 1; 15.8%, grade 2; 4.6% and grade 3; 1.8% Discussion Comparing results among trials is always difficult; however, despite that, in our series 58% of the cases were transplanted with active disease, our outcomes compare favorably with the results informed after the use of BEAM or CBV presented by CIBMTR in the largest trial published so far (table 1). The use of intermediate dose of carboplatin plus etoposide and cyclophosphamide produces a very good control of the lymphoma activity with acceptable toxicity, and achieves good OS and EFS. Other advantage of this regimen is that is carmustine free. The next step in our study is to do a matched paired analysis with patients transplanted with BEAM or CBV Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Low Incidence of Chronic Graft-Versus-Host Disease in Myeloablative Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Using Matched Related or Unrelated Donors: Phase II Study Interim Analysis

Introduction Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative treatment for many high-risk hematologic malignancies. Myeloablative conditioning is currently the standard of care for young and fit patients; however, graft-versus-host disease (GVHD) continues to be a major limitation to the success of HCT, increasing post-transplant morbidity and mortality. An ideal HCT is one combining strategies that reduce incidence and severity of GVHD, without compromising graft-versus-tumor effect. We hypothesized that GVHD prophylaxis regimen consisting of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac) and mycophenolate mofetil (MMF) will reduce the incidence of chronic GVHD in patients receiving a standard hematopoietic myeloablative HCT without an increase in risk of malignant relapse. Methods This is an interim analysis of a phase II study using a myeloablative preparative regimen of either: 1. total body irradiation (TBI, total dose 1320 cGy administered twice a day from days -4 to -1) or 2. Busulfan 3.2mg/kg daily (cumulative AUC 19,000 - 21,000 µmol/min/L) plus fludarabine 160mg/m 2 days -5 to -2 for patients unable to receive further radiation, followed by a GVHD prophylaxis regimen of PTCy (50mg/kg days +3 and +4), Tac and MMF (beginning day +5). The primary endpoint is cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment at 1 year post-transplant. Patient and disease characteristics are detailed in Table 1. Eligibility included: age ≤ 60 years, malignant or non-malignant diagnosis, matched related (MRD) or unrelated (MUD) donor with either a bone marrow (BM) or filgrastim-mobilized peripheral blood (PB) graft. Results Through October 2020 we treated 63 patients with a median follow up of 502 days post-transplant. Of those, 48% were female and n=11 (17%) younger than 18 with median age at HCT of 36 years (range, 2-55; Interquartile range [IQR], 20-48). Donor source was 8/8 MRD in 44 patients (70%), 8/8 MUD in 18 (29%), and one with 7/8 MUD. Graft source was BM in n=28 (44%) and PB in n=35 (56%). Preparative regimen was TBI in 94% of patients. All patients achieved primary neutrophil engraftment by 42 days, median 16 days (range, 13-27). Overall, 94% achieved platelet engraftment by 6 months, median 25 days (range, 16-98). At day 100, 48 patients (86%) achieved full donor bone marrow chimerism (>95% donor DNA); 29 (52%) and 52 (95%) achieved full donor peripheral blood CD3 and CD33 chimerism (defined as >95% donor). 42 patients (66%) required total parenteral nutrition (TPN) for oral mucositis and regimen-related toxicities during their initial transplant admission. Cumulative incidence of Grade II-IV acute GVHD by 100 days post-transplant was 14% overall (95% confidence interval CI: 6-23%), 7% for MRD and 32% for the MUD group; Grade III-IV acute GVHD was 5% overall (CI: 0-10%), similar for both MRD and MUD group. At 1 year, only two patients receiving a PBSC graft developed chronic GVHD requiring immune suppression, for a cumulative incidence of 3% overall, one in the MRD group and one in the MUD group. Two-year cumulative incidence of relapse was estimated at 21% overall, 22% and 16% for the MRD and MUD groups, respectively. Two year cumulative incidence of non-relapse mortality was 13% overall, 15% and 5% for MRD and MUD, respectively. Estimated 2-year overall survival was 79% overall (CI: 65-88%), 75% for the MRD group and 95% for MUD. Estimated 2-year GVHD-free relapse free survival (GRFS) was 57% overall (CI: 42-69%), 56% and 63% in the MRD and MUD groups, respectively. Discussion Myeloablative transplantation with a TBI preparative regimen, followed by a GVHD prophylaxis regimen of PTCy, Tac, and MMF results in very low incidence of chronic GVHD. Importantly, this regimen is feasible and effective for pediatric and adult patients. Further improvement in outcomes can be achieved by incorporating post-transplant relapse mitigating strategies as well as supportive care measures to decrease regimen-related toxicities. Figure 1 Figure 1. Disclosures Arora: Kadmom: Research Funding; Pharmacyclics: Research Funding; Syndax: Research Funding. Janakiram: Bristol Meyer Squibb, Kyowa Kirin, ADCT Therapeutics: Honoraria; FATE, Nektar Therapeutics: Research Funding. Smith: Astellas Gene Therapies: Current Employment. Bachanova: Incyte: Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Brunstein: BlueRock: Research Funding; AlloVir: Consultancy; FATE: Research Funding; NANT: Research Funding; GamidaCell: Research Funding. MacMillan: Equilium: Other: DSMB member; Incyte: Consultancy; Jazz Pharmaceuticals: Consultancy. Miller: Sanofi: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; ONK Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vycellix: Consultancy; GT Biopharma: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics, Inc: Consultancy, Patents & Royalties, Research Funding; Wugen: Membership on an entity's Board of Directors or advisory committees. Betts: Patent Disclosures: Patents & Royalties: B.C.B. holds a patent (WO2015120436A2) related to CD4+ T cell pSTAT3 as a marker and therapeutic target of acute GVHD. B.C.B. additionally holds a provisional patent (WO2017058950A1) related to the use of JAK inhibitors for rejection and GVHD prevention. . Vercellotti: Mitobridge, an Astellas Company: Consultancy, Research Funding; CSL Behring: Research Funding. Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding. Holtan: Generon: Consultancy; Incyte: Consultancy, Research Funding.

Outcomes of Cytomegalovirus Monitoring in Autologous Transplantation: A Single Institution Experience

Introduction: Identification of patients seropositive for cytomegalovirus (CMV) prior to stem cell transplant (SCT) is a well-accepted practice across institutions designed to reduce a known cause of morbidity and mortality in this population, but the role of monitoring and preemptive approaches to CMV identification and treatment are controversial and not standardized in autologous transplantation. The preemptive approach necessitates the use of significant resources and requires persistent patient involvement. Patients undergoing autologous SCT are at a relatively low risk for CMV reactivation, especially those seronegative for CMV at the time of transplant. Here, we show that the necessity of routine monitoring of autologous transplant patients is of minimal clinical value. Methods: To determine the efficacy of the CMV monitoring protocol currently in place at our institution in detecting patients who would later develop CMV reactivation and disease following autologous SCT, we retrospectively analyzed the charts of 218 adult patients between 11/1/14 and 8/1/19 who underwent transplant at St. Louis University Hospital. No patients underwent CD34 selected stem cell infusions. The protocol stipulated the following: CMV IgG/IgM and CMV DNA PCR prior to preparative regimen followed by weekly CMV DNA PCR to day +30 . We correlated the predictive ability of positive results on any of these screening tests to identify whether patients would later develop quantifiable CMV DNA PCR positivity, clinical manifestations of CMV disease, and/or require pharmacologic treatment for CMV. Results: Quantifiable pre-BMT DNA PCR was positive in only 0.46% of patients, and 97.79% of patients were DNA PCR negative prior to transplant. CMV IgG was positive in 56.4% patients, and only 22.1% of patients in this group went on to develop a quantifiable post-transplant PCR. Of the remaining 43.6% of patients initially testing negative for CMV IgG, no patients went on to develop a quantifiably positive post-transplant PCR. Regardless of seropositivity, only 0.08% of the 1,191 PCRs performed during the study period were found to be quantifiable. Further, no patients in our cohort developed CMV disease or required CMV treatment during the monitoring period. This trend persisted despite stratification by age, diagnosis, transplant number, and preparative regimen. Conclusion: When clinically-significant CMV is defined by cases requiring treatment or the development of end-organ disease, no screening tests performed elicited clinical action. Laboratory-based CMV surveillance, based on our data, has minimal diagnostic implications and represents an overly-stringent practice in a set of patients already utilizing a substantial share of healthcare resources. We believe that pre-transplant screening for CMV IgM serology and CMV DNA PCR can be safely eliminated in the autologous SCT population at our institution while CMV IgG still plays a role in determining candidacy for CMV-negative blood products. We also propose the elimination of serial post-transplant monitoring with DNA PCR in patients without clinical signs, symptoms, or pathologic findings suggestive of CMV disease. We have changed the protocol to test for CMV PCR only if there are clinical scenarios that indicate a utility, such as prolonged fever post-transplant, unexplained cytopenias, or unexplained pneumonitis, colitis, or hepatitis. By extension, other centers should consider determining the necessity of CMV screening in their autologous transplant population given the potential resource conservation and reduction in healthcare expenditures. Disclosures Fesler: abbvie: Consultancy, Speakers Bureau; incyte: Consultancy, Speakers Bureau; sanofi: Speakers Bureau; morphosys: Speakers Bureau; epizyme: Consultancy; jazz: Consultancy; Skipta: Consultancy; Best Doctors: Consultancy; Aptitude Health: Consultancy; Care Dx: Consultancy; Opinionsite: Consultancy. Goldenberg: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Lentivirus-mediated gene therapy for Fabry disease

Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34+-selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy.

A pragmatic multi-institutional approach to understanding transplant-associated thrombotic microangiopathy after stem cell transplant

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT). A single-center prospective screening study has shown that the incidence of TA-TMA is much higher than prior retrospective studies that did not systematically screen. These data have not been replicated in a multicenter study. Our objective was to determine the incidence and risk factors for TA-TMA and compare outcomes of pediatric HSCT patients with and without TA-TMA. Patients were prospectively screened for TA-TMA at participating centers using a simple to implement and inexpensive strategy from the start of the preparative regimen through day +100. TA-TMA was diagnosed if ≥4 of 7 laboratory/clinical markers diagnostic for TA-TMA were present concurrently or if tissue histology showed TA-TMA. A total of 614 patients (359 males; 58%) received prospective TA-TMA screening at 13 pediatric centers. TA-TMA was diagnosed in 98 patients (16%) at a median of 22 days (interquartile range, 14-44) posttransplant. Patients with TA-TMA had significantly increased bloodstream infections (38% [37/98] vs 21% [107/51], P ≤ .001), mean total hospitalization days (68; 95% confidence interval [CI], 63-74 vs 43; 95% CI, 41-45; P ≤ .001), and number of days spent in the intensive care unit (10.1; 95% CI, 6.4-14; vs 1.6; 95% CI, 1.1-2.2; P ≤ .001) in the first 100 days after HSCT compared with patients without TA-TMA. Overall survival was significantly higher in patients without TA-TMA (93%; 490/516) compared with patients with TA-TMA (78%; 76/98) (P ≤ .001). These data support the need for systematic screening for TA-TMA and demonstrate the feasibility and efficacy of an easy to implement strategy to do so.

Comparison of Individualized Versus MAP-Bayesian Predicted AUC of Busulfan in FluBu4 Treated Patients Undergoing Allogeneic Transplant

Although myeloablative fludarabine/busulfan (FluBu4) has been widely adopted in clinical practice, considerable interpatient variability exists in systemic busulfan exposure (AUC) when using body weight or body surface area based-dosing, leading to decreased efficacy (i.e. relapse) or increased toxicity (i.e., mucositis, veno-occlusive disease). This well-defined dose-exposure-outcome relationship has led to the widespread clinical implementation of therapeutic drug monitoring (TDM). However, individualized TDM can be time and labor intensive as well as potentially biased due to the lack of incorporation of any previously established PK data (Bayesian prior). In contrast, Bayesian maximum a posteriori (MAP) PK models consider the Bayesian prior and individualized TDM to generate a revised probability distribution (Bayes conditional posterior) to more accurately and rapidly estimate the AUC with reduced bias. There are a paucity of data comparing busulfan AUCs using individualized PK versus MAP-Bayesian-based models in adults although these more sophisticated approaches may assist in optimizing dosing of busulfan in this vulnerable population. This was a retrospective, single-center study of patients who received FluBu4 with busulfan TDM between January 1999 and September 2019. 109 patients diagnosed with a hematologic malignancy who received either sequential (n=46) or concurrent (n=63) FluBu4 were analyzed. The median age was 48 (range: 18-66), and were Hispanic (n=38), White (n=46) or African-American (n=14). TDM was performed either after a test dose of 0.8 mg/kg (n=52) or after the first dose (3.2 mg/kg) of busulfan administered during the preparative regimen (n=71), with dosing was based on actual or adjusted body weight. For PK analysis, plasma busulfan concentrations were analyzed via gas chromatography with mass selective detection. Individualized PK data were generated using WinNonlin while the MAP-Bayesian approach utilized the Bayesian prior developed from McCune et al (Clin Cancer Res, 2014). An AUC of 4800 µM˖min/24 hours was targeted based on previous literature. Based on individualized PK data, total recommended busulfan doses ranged from 9.3-21.3 mg/kg (-27.1% to +66.7% compared to FDA labeled dose of 12.8 mg/kg). When first-dose busulfan PK was compared between busulfan given sequentially versus concurrently with fludarabine there was a trend towards a higher AUC with concomitant administration (4651 vs. 4988 µM˖min; p=0.13). A strong correlation between the AUC generated from both the individualized PK an MAP-Bayesian models was observed with both the test dose (R2=0.91) and first dose (R2=0.86) of busulfan. Using the MAP Bayesian model, AUC predictions were on average higher (mean AUC 5069 versus 4886 µM˖min, p<0.0001) compared to the patient-specific individualized PK estimates. Figure 1 shows the Bland Altman plots for comparison of the individualized AUC vs. MAP-Bayesian estimates for test dose and first dose. Our individualized busulfan PK approach generated relatively similar AUC values compared to MAP-Bayesian estimates, although the higher AUC generated via MAP-Bayesian predictions may allow for lower doses of busulfan to be administered thereby potentially reducing toxicity while maintaining efficacy. Further, use of the MAP-Bayesian method may allow for more rapid dose optimization and a decreased number of serum concentrations. Further prospective studies including more patients are warranted to confirm these findings. Figure 1 Disclosures Calip: Flatiron Health: Current Employment. Patel:Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy.

Trial in Progress: A Prospective Phase I/II Trial to Jointly Optimize the Administration Schedule(s) and Dose(s) of Melphalan for Injection (Evomela) As a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

Background: High-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) is considered to be the standard of care treatment for transplant-eligible patients with multiple myeloma (MM). The most commonly used conditioning regimen in this setting is high-dose melphalan by intravenous administration. Conventional melphalan formulations, when administered at high doses, can put patients at risk of potential propylene glycol-associated toxicities. Melphalan for injection (Evomela) is propylene glycol free (PGF), can be dissolved directly using saline, and as a PGF reformulation of Alkeran, incorporating Captisol brand of beta-cyclodextrin sulfobutyl ethers sodium salts, overcomes previous formulation limitations. In 2016 Evomela was the first product approved by the US FDA for high-dose conditioning treatment prior to HCT in MM patients and it is also indicated for the palliative treatment of patients with MM for whom oral therapy is not appropriate. Reconstituted Evomela solution can be stored in the vial for up to 1 hour at room temperature or up to 24 hours at 2-8 °C with no significant degradation. After storage in the vial, it remains stable for an additional 3 to 29 hours after, preparation of admixture solution in infusion bags at concentrations of 0.25 to 5.0 mg/mL, respectively. As well, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan, was bacteriostatic through 72 hours when stored at 2-8 °C. This stability allows for less frequent handling by pharmacy and nursing staff, resulting in a concomitant decrease in exposure risks, increased convenience and administration flexibility, suggestive of an improved ease of handling and administration, when compared to Alkeran. Further, Evomela may actually be less toxic due to the absence of propylene glycol. Although increased melphalan doses have previously demonstrated signals of improved response, the most commonly used dose of melphalan is 200 mg/m2, primarily due to concerns of toxicity. Emerging data regarding higher stability and potentially less toxicity of PGF melphalan (Evomela) supports dose escalation evaluation in order to improve the outcomes. Previous trial data have shown that continuous infusion or frequent fractionated-dose delivery increases the antitumour activity of several drugs. Due to the instability of currently available Alkeran at the room temperature, infusional studies have not been feasible. This limitation is overcome by Evomela, being that the compound is stable for several hours at the room temperature, thus allowing evaluation of infusional schedules in addition to the traditional 30-60 minute bolus doses. Here, we describe a trial designed to assess whether the above noted characteristics of Evomela allow for the escalation of dose and prolongation of infusion time, in order to increase the efficacy of melphalan in patients undergoing auto-HCT. Study Design/Methods: This is a two-stage phase I-II trial to optimize the dose and schedule of Evomela given as a single agent preparative regimen for auto-HCT. Up to 60 participants may be included if they are 18-70 years of age, with non-relapsed MM, have a Karnofsky performance score ≥70%, who have received at least two cycles of initial systemic therapy, and are within 2 to 12 months of the first dose. Patients will be randomized 1:1 to two different infusion schedules (30-60 minute infusion or 8-9 hour infusion) using Evomela (2mg/ml) at two dose cohorts (200mg/ml2 or 225mg/m2). Because 2 mg/mL Evomela is stable for 10 hours, patients receiving the 8-9 hour infusion will receive the total dose in one single infusion bag. The primary objectives are to determine the optimal dose and schedule of Evomela before auto-HCT for MM and collect pharmacokinetic data and compare the exposure-response evaluations between the two infusion schedules. Secondary outcomes will include incidence of treatment-related mortality, rate of minimal residual disease negative complete response at 90 days post auto-HCT, progression-free survival and overall survival after auto-HCT in newly diagnosed myeloma patients treated on different schedules and doses of Evomela. The active study follow-up period will be up to one-year post auto-HCT. Figure Disclosures Bashir: Acrotech: Research Funding; StemLine: Research Funding; Takeda: Other: Advisory Board, Research Funding; Celgene: Research Funding; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board. Qazilbash:Amgen: Research Funding; Bioclinica: Consultancy; Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding.

Burden of Illness and Outcomes in the 2nd Line Treatment of Large B-Cell Lymphoma: A Real-World Comparison of Medicare Beneficiaries with and without Stem Cell Transplants

Introduction: Standard first line therapy (LOT) for patients (pts) with large B-cell lymphoma (LBCL) involves chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or a similar regimen, e.g. R-CHOP with the addition of etoposide (R-EPOCH). While most pts respond, 30-40% of pts relapse or fail to achieve remission with 1st LOT. For those pts, the goal of curative 2nd LOT is typically platinum-based salvage chemotherapy in preparation for autologous stem cell transplant (ASCT). However, many pts (50% or more) do not qualify for intensive therapy, either due to age or comorbidities, or because they do not respond to or cannot tolerate salvage chemotherapy. For those further treatment options are limited. Objectives: In a sample of U.S. LBCL pts 65 and older, who have progressed to 2nd LOT and are eligible for ASCT, to compare the patient characteristics, treatments, costs and overall survival between pts who received SCT with those who did not. Methods: This retrospective cohort study used 100% Medicare Fee-for-Service Parts A/B claims data and Part D Prescription Drug Event data to identify pts ≥ 65 years of age, newly diagnosed with LBCL in 2012-2017, and who had ≥ 6 months continuous enrollment pre-diagnosis (baseline) and ≥ 12 months post-diagnosis, or who died after initiation of 2nd LOT. All were treated with a CHOP-like regimen 1st LOT and progressed to 2nd LOT. Eligible pts who received a 2nd LOT with a SCT-preparative regimen per NCCN guidelines were stratified into the "ASCT-intended" cohort, and the remainder into the "ASCT-not-intended" cohort. The ASCT-intended group was further subset into those who received a SCT and those who did not (Non-SCT). These 2 subsets formed the primary comparison groups. Baseline characteristics were age, gender, race, dual eligibility status (i.e. Medicare plus Medicaid), and Charlson-Deyo Comorbidity Index (CCI). Measures of utilization during follow-up (from initiation of 2nd LOT to loss to follow-up) were hospitalizations, outpatient and emergency department (ED) visits, and post-acute care. Costs during follow-up reflected standardized, inflation-adjusted, all-cause paid amounts. Utilization and cost metrics were standardized to per-patient-per-month (PPPM). Overall survival (OS) was measured from the start of 2nd LOT until death, disenrollment or the end of the study period. Results: 4,758 pts met all inclusion criteria. 3,713 (78%) did not receive a SCT-preparative regimen after 1st LOT. 1,045 pts (22%) received a SCT-preparative regimen and constituted the ASCT-intended group. Of these, 244 (23.3%) received a SCT and 801 (76.7%) did not. The remainder of this report focuses on a comparison of the SCT and non-SCT cohorts. Baseline characteristics, treatments, utilization and cost are summarized in Table 1. Both groups were predominantly white, but SCT pts were, on average, 5 years younger, slightly more likely to be male, and had slightly lower mean CCI scores. 13.1% of non-SCT pts were dual eligible vs. 4.5% of SCT (all p < .01 except Race). 93.9% of SCT procedures were autologous, and no pts had more than 1 SCT during follow-up. Non-SCT pts had higher all-cause utilization for all categories except for acute hospitalizations. The higher inpatient utilization for the SCT group may reflect the SCT procedure itself (94% of SCT were inpatient). A similar pattern was observed in the cost data, where Non-SCT pts incurred higher costs except for acute hospitalizations. Results for OS are summarized in Figure 1. Non-SCT pts had significantly lower rates of survival than SCT pts. 94.7% of SCT pts were still alive 6 months after initiation of 2nd LOT, whereas only 66.9% of non-SCT pts were. At two years post-2nd LOT, survival rates were 69.7% vs. 36.3%. Conclusions: In this study, only 23.3% of SCT-intended pts ultimately received it. The remaining 76.7% were SCT-intended but never received a transplant. Compared to the SCT pts, the non-SCT pts were older, had more comorbidities, had higher rates of healthcare utilization and costs post-2nd line therapy in all categories (except acute inpatient), and lower OS. 38.7% of non-SCT pts proceeded to additional lines of lymphoma-directed therapies beyond 2nd line, which may suggest that their clinicians felt that there was potential benefit to further treatment. These data suggest there may be unmet need for elderly pts with LBCL who are eligible for ASCT, but do not ultimately receive it. Disclosures Kilgore: Kite, A Gilead Company: Research Funding. Wong:Kite, A Gilead Company: Research Funding. Thornton Snider:Precision Medicine Group: Ended employment in the past 24 months, Research Funding; Gilead Sciences: Current equity holder in publicly-traded company, Research Funding; Kite, A Gilead Company: Current Employment. Cheng:Kite, A Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Schroeder:Kite, A Gilead Company: Research Funding. Mohammadi:Kite, A Gilead Company: Research Funding.