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CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

PURPOSE: If identifiable, potentially avoidable hospitalizations (PAHs) can serve as an important target for cost containment efforts in oncology. METHODS: PAHs among a cohort of Medicare patients with prostate cancer were identified using a two-stage consensus-driven review process. In stage 1, two clinicians independently evaluated admissions records using a case review form, which we modified from a previous study to assess for PAHs. In stage 2, any admissions that the reviewers disagreed on or were unsure of were re-examined in a larger group of clinicians to yield a consensus determination regarding avoidability. Univariable and multivariable regression analyses were performed to identify factors predictive of PAH. RESULTS: There were 160 admissions among this cohort of 210 patients from January 2012 to June 2015, of which 99 were evaluable. Consensus-driven clinical review yielded an overall PAH rate of 28.3%. Factors associated with increased PAH risk were admission for symptoms related to cancer (odds ratio [OR], 7.33; P < .001), presence of a social contributor to admission (OR, 4.40; P = .014), and history of alcohol or drug abuse (OR, 4.93; P = .025). Admission for a noncancer condition was associated with decreased PAH risk (OR, 0.32; P = .011). On multivariable analysis, presence of a social contributor to admission (OR, 9.35; P = .002) and admission as a result of a noncancer condition (OR, 0.16; P = .038) remained predictive of PAH risk. CONCLUSION: A significant proportion of hospitalizations among patients with prostate cancer are potentially avoidable. Understanding factors predictive of risk for PAH can help inform programs aimed at avoiding such admissions to improve overall care quality and value.

Graft-versus-host disease has been reported to occur rarely in syngeneic hematopoietic stem cell transplant recipients. Clinical and histological changes consistent with graft-versus-host disease have been reported to occur in this patient population. We report a case of a 46-year-old Caucasian male with diffuse large B-cell lymphoma in complete remission who underwent a syngeneic hematopoietic stem cell transplant. He was diagnosed with grade III acute skin and gastrointestinal graft-versus-host disease requiring high-dose corticosteroids and immunosuppressive therapy and resulting in a complete response. Syngeneic graft-versus-host disease is an anomaly that needs to be considered as a differential diagnosis of patients experiencing dermatitis, gastroenteritis, or hepatitis after an identical twin hematopoietic stem cell transplant.

PURPOSE: As expenditures for cancer care continue to grow substantially, value-based payment models are being tested to control costs. The Oncology Care Model (OCM) is the largest value-based payment program in oncology. The primary objective of this analysis was to determine the impact of high-cost novel agents on total cost of care for multiple myeloma (MM) episodes of care in the OCM. METHODS: This was a retrospective analysis using Medicare claims data for 258 MM OCM episodes initiated between July 1, 2016, and July 1, 2017. Patients were organized into 3 cohorts: those who received pomalidomide (cohort A), those who received lenalidomide (cohort B), and those who did not receive either drug but had received another chemotherapy agent (cohort C). We compared the actual episode expenditures and the Centers for Medicare and Medicaid target price to create an observed versus expected (O/E) ratio. RESULTS: The average O/E for cohort A (n = 73) was 1.73, compared with 1.31 for cohort B (n = 84) and 1.01 for cohort C (n = 101). The difference the in O/E ratio among the groups was statistically significant ( P < .001). The average episode target price for cohorts A, B, and C was $66,149, $63,483, and $63,937, respectively. Despite the high cost of pomalidomide and lenalidomide, there was no significant difference in the average episode target prices of the cohorts. CONCLUSION: The O/E ratio and target prices of the cohorts demonstrate a lack of adequate adjustment to the OCM target price for episodes in which pomalidomide and lenalidomide were used to treat patients with MM.

Purpose/Objectives We sought to estimate the expected cost savings generated if a set of potentially avoidable hospitalizations (PAHs) among oncology care model (OCM) patients with prostate cancer were shifted to an acute care model in the outpatient setting. Methods We previously identified a set of 28 PAHs among OCM prostate cancer patients. Outpatient management costs for a characteristically similar cohort of cancer patients were obtained from our institution’s ambulatory acute-care Oncology Care Unit (OCU). We excluded OCU visits resulting in hospitalization, involving non-cancer diagnoses, and those missing clinical/financial information. Exact-matching based on the strata of age, categorically-defined presenting complaint, and systemic disease was used to match PAHs to OCU acute care visits. PAH costs obtained from OCM data were compared to costs from matched OCU visits. Results We identified 130 acute care OCU visits, of which 47 met inclusion criteria. Twenty-four PAHs (89%) matched to 26 of these OCU visits. PAHs accounted for 5.8% of OCM expenditures during our study period. The mean inpatient cost among matched PAHs was $15,885 compared to $6227 for matched OCU visits. Boot strapping within each match stratum produced a mean estimated cost savings of $12,151 (95% CI $10,488 to $13,814) per PAH. We estimate this per event savings to yield a 4.4% (95% CI 3.8% to 5.0%) an overall spending decrement for OCM prostate cancer episodes. Conclusions PAHs contribute meaningfully to costs of care in oncology. Investment in specialized ambulatory acute care services for oncology patients could lead to substantial cost savings.

In the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival and an increase in second primary malignancies for lenalidomide at a median follow-up of 34 months. Here we report an updated intention-to-treat analysis of CALGB (Alliance) 100104 at a median follow-up of 91 months.Patients were eligible for this randomised, double-blind, placebo-controlled, phase 3 trial if they had symptomatic disease requiring treatment; had received, at most, two induction regimens; and had achieved stable disease or better in the first 100 days after ASCT. We randomly assigned patients to either lenalidomide or placebo groups using permuted block randomisation, with a fixed block size of six. Randomisation was stratified by three factors: normal or elevated β2 microglobulin concentration at registration (≤2·5 mg/L vs2·5 mg/L), previous use or non-use of thalidomide during induction therapy, and previous use or non-use of lenalidomide during induction therapy. The starting dose was two capsules (10 mg) per day, escalated to three capsules (15 mg) per day after 3 months. The primary endpoint was time to progression (time of progressive disease or death from any cause), with intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00114101. New patients are no longer being recruited, but some patients remain on treatment and in follow-up.Between April 14, 2005, and July 2, 2009, 460 patients were randomly assigned to receive either lenalidomide (n=231) or placebo (n=229). After three interim analyses, the study was unblinded at a median follow-up of 18 months, at which point 86 (67%) of 128 patients without progressive disease in the placebo group chose to cross over to the lenalidomide group. The median follow-up for the updated survival analysis, as of Oct 19, 2016, was 91 months (IQR 83·6-103·1). The median time to progression was 57·3 months (95% CI 44·2-73·3) for the lenalidomide group and 28·9 months (23·0-36·3) for the placebo group (hazard ratio 0·57, 95% CI 0·46-0·71; p0·0001). The most common grade 3-4 adverse events were neutropenia (116 [50%] patients in the lenalidomide group and 41 [18%] patients in the placebo group) and thrombocytopenia (34 [15%] patients in the lenalidomide group and 12 [5%] patients in the placebo group). 18 (8%) haematological and 14 (6%) solid tumour second primary malignancies were diagnosed after randomisation and before disease progression in the lenalidomide group, compared with three (1%) haematological and nine (4%) solid tumour second primary malignancies in the placebo group. Three haematological and five solid tumour second primary malignancies in the placebo group were in the crossover subgroup.Despite an increase in haematological adverse events and second primary malignancies, lenalidomide maintenance therapy after ASCT significantly improved time to progression and could be considered a standard of care.The National Cancer Institute.

Myelofibrosis (MF) is a chronic progressive hematologic malignancy with a median overall survival (OS) of approximately 6 years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the sole treatment approach that offers curative potential. The use of reduced-intensity conditioning regimens has expanded the application of HSCT to patients with MF up to age 70 years. Recent retrospective and prospective reports have suggested worse HSCT outcomes for patients with MF receiving an unrelated donor graft compared with those receiving a related donor graft. To identify patient- and HSCT-specific variables influencing outcomes, we conducted a retrospective analysis of 42 patients with chronic and advanced-phase MF who underwent HSCT at our institution. For this cohort, at a median follow-up of 43 months, progression-free survival (PFS) was 15 months and OS was 25 months. In multivariable analysis, the sole clinical variable that negatively influenced outcome was the use of an unrelated donor, with a median PFS and OS both of 11 months versus not yet reached in patients receiving a related donor graft. At 2 years, OS was 38% (95% confidence interval [CI], 20%-56%) and nonrelapse mortality (NRM) was 53% (95% CI, 36%-78%) in the unrelated donor graft group, compared with 75% (95% CI, 46%-90%) and 21% (95% CI, 9%-47%) in the related donor graft group. There was no difference in the rates of grade III-IV acute graft-versus-host disease between the unrelated and related donor groups (38% versus 38%). Despite a more aggressive disease state, 2-year PFS and OS were both 42% (95% CI, 15%-67%) in patients with myeloproliferative neoplasm-blast phase undergoing HSCT. Graft failure rate was higher in patients receiving a mismatched donor graft compared with those receiving a matched donor graft (60% versus 13%; P = .0398). Retransplantation of patients with graft failure resulted in long-term survival. Baseline splenomegaly did not affect transplantation outcomes. Given the particularly poor outcomes seen in the unrelated donor cohort here and elsewhere, a formal exploration of alternative hematopoietic stem cell sources is warranted.

Relapse remains the major cause of death in older patients transplanted for acute myeloid leukemia (AML) in first complete remission or for patients with advanced myelodysplastic syndrome (MDS) at any age. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with reduced-intensity conditioning when performed in younger patients with AML or MDS, but the toxicity of this approach in older patients is prohibitive. We hypothesized that pharmacokinetic targeting to optimize busulfan (BU) exposure, combined with the administration of azacitidine (AZA) post-transplant would mitigate the risk of relapse while reducing nonrelapse mortality and ultimately improve progression-free survival (PFS). On this phase II multicenter study, 63 patients (40 unrelated donors and 23 matched related donors) received a uniform conditioning regimen consisting of fludarabine i.v. (days –7 to –3), BU targeted to a daily area under the curve (AUC) of 4000 μM/min (days –6 to –3) after the administration of a 25-mg/m2 i.v. test dose on 1 day between days –14 to –9, and antithymocyte globulin (days –6, –5, and –4 (2 doses for matched related donors and 3 for matched unrelated donors only). Beginning on days +42 to +90, all patients were planned to receive up to 6 monthly cycles of AZA at 32 mg/m2 subcutaneously for 5 days. The median age was 62 years (range, 44 to 74); 13 had AML and 50 had MDS; 87% of patients were within 20% of the target AUC based on a validation sample. Forty-one patients (65%) started AZA at a median of 61 days (range, 43 to 91) post-transplant, and 17 patients (41%) completed all 6 cycles of AZA. The cumulative incidence of nonrelapse mortality at 2 years was 33.4% (95% confidence interval [CI], 22%-45%). The cumulative incidence of relapse was 25% (95% CI, 15%-37%) at 2 years. With a median follow-up of 58.9 months, the estimated PFS probability at 2 years and 5 years after transplantation was 41.2% (80% CI, 33.9%-49.9%) and 26.9% (80% CI, 20.4%-35.5%), respectively, for the entire group with a median PFS of 15.8 months (95% CI, 6.7 to 28.3). The probability of overall survival at 2 and 5 years was 45.7% (95% CI, 34.9%-59.9%) and 31.2% (95% CI, 21.3% to 45.8%), respectively, for the entire group with a median overall survival of 19.2 months (95% CI, 8.7 to 37.5). In summary, we demonstrated the feasibility of a novel reduced-intensity conditioning regimen with test dose BU targeted to an AUC of 4000 μM/min. The feasibility of AZA in this setting appears to be limited if applied to an unselected population of older hematopoietic stem cell transplantation recipients. (ClinicalTrials.gov Identifier: NCT01168219.)

PURPOSE: The Oncology Care Model (OCM) must be clinically relevant, accurate, and comprehensible to drive value-based care. METHODS: We studied OCM data detailing observed and expected expenses for 6-month-long episodes of care for patients with prostate cancer. We constructed seven disease state–treatment dyads into which we grouped each episode on the bases of diagnoses, procedures, and medications in OCM claims data. We used this clinical-administrative stratification model to facilitate a comparative cost analysis, and we evaluated emergency department and hospital utilization and drug therapy as potential drivers of cost. RESULTS: We examined 377 episodes of care, pertaining to 210 patients, that took place within our health system from January 2012 to June 2015. Ninety-six percent of episodes were assigned to clinically meaningful dyads. Excessive expenses were seen in metastatic, castration-resistant dyads containing second-line hormone therapy (ratio of observed to expected expenses [O/E], 2.66), chemotherapy (O/E, 2.09), and radium-223/sipuleucel-T (O/E, 3.01). An OCM update correcting for castration-resistant prostate cancer led to small differences in observed expenses (0% to +2%) but large changes in expected expenses (−17% to −27% for hormone-sensitive dyads and +136% to +141% for castration-resistant dyads). O/E increased up to 38% for hormone-sensitive dyads and decreased up to 58% for castration-resistant dyads. Emergency department and hospital utilization seems to drive cost for castration-resistant dyads but not for hormone-sensitive dyads. In the revised OCM model, overall O/E for all episodes improved by 22%, from 1.48 to 1.15. CONCLUSION: Our experience with OCM highlights the limitations of administrative claims data within this model and illustrates a method of translating these data into clinically meaningful information to improve value.

Antibiotic stewardship is an integral aspect of hospital care, limiting the potential for resistance while working to minimize waste. A similar system is needed in oncology, given the rapid proliferation of new therapies and the challenges of navigating a complicated reimbursement environment. A "cancer therapy stewardship program" has never been described in the literature. Here, we detail our efforts to design and implement such a program and share lessons learned to inform future projects.For 1 year, a hematologist-oncologist (the "cancer therapy steward") at Mount Sinai Hospital was in charge of addressing all requests for nonformulary or off-label chemotherapeutic and supportive medications and regimens. Requests consisted of the rationale for use and supporting data from medical journal articles. This pilot initiative was focused mainly on inpatient malignant hematology.Sixty-seven requests were made by 23 physicians, and all requests were ultimately approved. Requests tended to fall into 3 categories: 1) use of a single drug in a setting not approved by the FDA, 2) use of multiple drugs in novel combinations not approved by the FDA, and 3) adding novel drugs to existing FDA-approved regimens.Our cancer therapy stewardship program yielded many useful insights into how our physicians face challenging clinical situations. It also helped to improve overall clinical quality and patient care by emphasizing the importance of value-based care and evidence-based medicine. Expanding this program will likely lead to many interesting experiments aimed at improving medical education and research, patient safety outcomes, and clinical quality.

Background aims Stem cell collection can be a major component of overall cost of autologous stem cell transplantation (ASCT). Plerixafor is an effective agent for mobilization; however, it is often reserved for salvage therapy because of its high cost. We present data on the pharmacoeconomic impact of the use of plerixafor as an up-front mobilization in patients with multiple myeloma (MM). Methods Patients with MM who underwent ASCT between January 2008 and April 2011 at the Mount Sinai Medical Center were reviewed retrospectively. In April 2010, practice changes were instituted for patients with MM to delay initiation of granulocyte-colony-stimulating factor (G-CSF) support from day 0 to day +5 and to add plerixafor to G-CSF as an up-front autologous mobilization. Targets of collection were 5–10 × 10 6 CD34 + cells/kg. Results Of 50 adults with MM who underwent ASCT, 25 received plerixafor/filgrastim and 25 received G-CSF alone as an up-front mobilization. Compared with the control, plerixafor mobilization yielded higher CD34 + cell content (16.1 versus 8.4 × 10 6 CD34 + cells/kg; P = 0.0007) and required fewer sessions of apheresis (1.9 versus 3.1; P = 0.0001). In the plerixafor group, the mean number of plerixafor doses required per patient was 1.8. Although the overall cost of medications was higher in the plerixafor group, the cost for blood products and overall cost of hospitalization were similar between the two groups. Conclusions Up-front use of plerixafor is an effective mobilization strategy in patients with MM and does not have a substantial pharmacoeconomic impact in overall cost of hospitalization combined with the apheresis procedure.

298 Background: A comprehensive chemotherapy informed consent process improves shared decision-making. Additionally, the Oncology Care Model (OCM) emphasizes providing patients with a documented care plan that contains the 13 components in the Institute of Medicine Care Management Plan. Within our health system, we incorporated the care plan into our existing chemotherapy consent process and utilized technology to increase compliance and reduce administrative burden. Methods: Our 2 phase PDSA included: 1) updating our existing paper chemotherapy form with the 13 components of the IOM care plan and then 2) piloting an electronic version of the chemotherapy consent form. We updated our new chemotherapy consent with the addition of Prognosis, Expected Response to Treatment, Potential Effect on Quality of Life, Potential Benefits/Goals of Treatment, and added more options for potential side effects/harm. Given the increased administrative burden, we created and piloted the use of an electronic version of the consent form in our breast oncology program. Results: Baseline, monthly random chart audit of 20-40 patients revealed compliance with completing every question of the paper chemotherapy consent at 30% of all patients receiving IV chemotherapy at our cancer center that month- 7/2018. When the new chemotherapy consent incorporating the IOM elements was rolled out, compliance initially rose to 50% (8/2018), however the following months dropped to 10-20% (9-11/2018) and then back up to 41% briefly (12/2018). The results were low and inconsistent. A pareto chart confirmed that redundancy and too many questions were the reasons for under-completion. By auto-populating fields for certain questions on the paper consent, compliance increased to 75% (2/2019). Finally within our breast cancer pilot group our compliance rose to 100% (3-4/2019), by converting to an electronic form with the maximum options for auto-population and drop-down selections for certain fields. Conclusions: Incorporating regulatory requirements into an existing workflow can reduce administrative burden. The use of innovative technology can further increase clinician and OCM compliance while delivering value to patients.

114 Background: Hospital-based care remains a major contributor to cost in oncology and thus represents an important cost-saving opportunity. We previously developed a rigorous two-stage consensus driven review process to identify potentially avoidable hospitalizations (PAHs) among oncology care model (OCM) patients with prostate cancer and reported a 28% rate of PAHs between 1/2012-6/2015. Our current objective was to estimate the magnitude of any expected cost savings generated if inpatient care from these PAHs were shifted to an acute care model in the outpatient setting. Methods: Costs for ambulatory acute care management among a separate but characteristically similar cohort of cancer patients were obtained from our institution’s recently established Oncology Care Unit (OCU), where acute clinical issues are managed in an enhanced ambulatory setting. We used an exact-matching algorithm to match previously identified PAHs to OCU visits based on strata of age (≤ 70 years vs. > 70 years), categorically defined chief complaint (infusion/transfusion, lab abnormalities, symptom control, and diagnostic work-up), and the presence of “systemic disease” (metastatic disease or hematologic malignancy). PAH costs obtained from OCM data were compared to costs from these matched OCU encounters. Results: We identified 89 acute care OCU visits occurring from 5/2017-12/2018, of which 48 were fully evaluable based on documentation. Twenty-five of our initial 28 PAHs (89%) matched to 29 OCU acute care visits. The mean inpatient cost among matched PAHs was $15,879 compared to $975 for matched OCU visits. Boot strapping within each match produced a mean estimated cost savings of $15,120 (95% CI $13,682 to $16,557) per PAH. We estimate this per event savings to yield an overall spending decrement of 5.7% for OCM prostate cancer episodes. Conclusions: PAHs contribute substantially to costs of care in oncology. Investment in specialized ambulatory acute care services for oncology patients could lead to meaningful cost savings by shifting avoidable inpatient care to the outpatient setting.

Background: In July of 2016, CMMI started a five year bundled payment program called OCM. Beneficiaries are attributed to practices providing their cancer care for a 6 month episode triggered by the administration or distribution of specified cancer drugs. The model provides risk adjustments to the target price based on risk factors such as age, chemotherapy and the receipt of certain treatments (radiation or bone marrow transplant). Target prices are adjusted by geographic region, novel therapy use, and a trend factor. Multiple Myeloma was identified in our practice as a cancer type with high variance on expenditures after the first Performance Period within the model (July 2016-December 2016). Chemotherapy represented 52% of total episode expenditures with oral chemotherapy and hormone therapy representing 24%. The average cost of lenalidomide for one year is $115,000. The model adjusts for novel therapies, including new drugs approved by the FDA after December 31, 2014 with status lasting two years. However, literature demonstrates that this does not fully adjust for the high costs of novel therapies (Muldoon et at., Health Affairs, 2018). Unlike solid tumors, Multiple Myeloma staging may not improve risk adjustment and target price. Methods: We analyzed the total cost of care of beneficiaries who triggered an OCM episode for Performance Period 1 (PP1). Beneficiaries were identified by diagnosis of Multiple Myeloma, and then segregated into cohorts of those who received lenalidomide and/or pomalidomide and those who did not. Observed vs. Expected (O/E) target price for each episode was determined for both cohorts comparing the actual episode expenditures and the target price per episode calculated by the Oncology Care Model. A two sample t-test was conducted followed by a linear regression to determine relation between drug days prescribed and O/E. Results: There were 125 attributed beneficiaries with a Multiple Myeloma diagnosis who triggered an episode during PP1. The average O/E of the cohort which received the chemotherapy, Cohort A, was 1.624 compared to 0.986 for those that did not, Cohort B. The difference in average O/E in the two cohorts was 39% higher in Cohort A, p Discussion: This is the first report on the impact of lenalidomide and pomalidomide on the total cost of care in an OCM practice. The results demonstrate the lack of adequate adjustment to the CMS target price for episodes in which one or both of these drugs were prescribed. Lenalidomide and pomalidomide are first and second line drugs used both for induction and maintenance. Both drugs are frequently used for prolonged periods of time in patients and trigger more than one episode in OCM. Therefore, the use of these agents greatly affects the total cost of care against a target price that is not adequately adjusted. Academic Medical Centers that care for larger populations of multiple myeloma patients may be disproportionately affected and this will impede their success under the OCM methodology. Additional analysis similar to this will inform CMMI as to further refinements to the OCM adjusters. Disclosures No relevant conflicts of interest to declare.

Purpose Acute lymphoblastic leukemia (ALL) has a predilection for CNS involvement. Patients with high-risk ALL are often managed with transplant using a radiation-based conditioning regimen. Historically, a high-dose prophylactic cranial boost (CB) of ≥12 Gy was given to reduce risk of central nervous system (CNS) recurrence. However, the use of CB has fallen out of favor because of toxicity concerns. In high-risk adults undergoing transplant at our institution, we have used a low-dose 6 Gy CB to reduce toxicity while conditioning adults with fully developed brains. The safety, efficacy, and utility of a low-dose CB in adults are poorly studied; herein, we report their outcomes and toxicity. Methods and materials We identified all high-risk ALL patients undergoing total body irradiation as part of their conditioning regimen. Those who received 6 Gy CB or no CB were included (55 total). Their charts were reviewed and statistical analyses were completed with R, version 2.15.2. Results In patients undergoing CB, 3-year CNS disease-free survival and overall survival were 94.7% and 62.7%. In those not undergoing CBs, survivals were 81.8% and 51.5%. Notably, within the CB cohort, patients without prior CNS involvement had no CNS failures. In contrast, in the non-CB cohort, there were 2 CNS failures in patients with no history of CNS involvement. In the CB cohort, the only notable acute toxicity was parotitis (2.8%). Late toxicity in the CB cohort included 1 instance of cataracts (2.8%) without any evidence of cognitive impairment or potential radiation induced secondary malignancy. Conclusions A dose of 6 Gy CB is well-tolerated in the adult ALL population as part of a radiation-based conditioning regimen. Low-dose CB may be considered in adult patients with high-risk ALL without prior CNS involvement to reduce the likelihood of recurrence.

46 Background: Hospitalization is a major contributor to cost in oncology. Minimizing avoidable admissions can lead to substantial savings. Methods: We studied Medicare claims data from 160 admissions for prostate cancer (PCa) patients from 1/2012 to 5/2015. Admissions with the lowest 50th percentile of charges were assessed for being potentially avoidable by 2 independent chart reviews; remaining admissions were assumed to be unavoidable due to medical complexity. Common admitting diagnoses were targeted by theoretical care pathways designed to minimize avoidable admissions via expedited outpatient follow-up. We compared the cost of the avoidable admissions to that of implementing 3 such pathways then estimated the financial impact. Results: Total cost for all 160 admissions was $1,979,200. 25% of these admissions, accounting for $494,800, were deemed potentially avoidable. Our model exchanged each of these admissions for a routine clinic visit which led to an estimated $464,800 in savings, or a 23% improvement in total cost. The most common admitting diagnoses were fever (18%), pain (12%), and dehydration (8%). On review, 3/9 fever admissions in this set were deemed avoidable with 1 extra clinic visit, 3 with 3 visits, and 3 were unavoidable, yielding a 53% reduction in cost for this diagnosis. Similar analyses led to cost reductions of 75% and 66% for pain and dehydration admissions, respectively. Combining just these 3 theoretical interventions led to an estimated savings of $146,955, or a 7.4% improvement in total cost. Conclusions: A sizable portion of PCa admissions can be avoided, with ample savings, if a system is in place to provide the additional care that often exceeds the capabilities of a busy practice. [Table: see text]

We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P

Umbilical cord blood (UCB) offers many potential advantages as a source of hematopoietic stem cells (HSCs) for allogeneic transplantation, including ease of collection, rapid availability, flexibility of HLA-matching, lower rates of GvHD and potentially lower relapse rates. However, the low HSC content of UCB compared to other graft sources results in a prolonged time to engraftment, and higher rates of graft failure and early mortality. Pulse ex vivo exposure of HSCs to 16,16-dimethyl PGE2 (FT1050) has been demonstrated to enhance HSC engraftment potential, which could benefit clinical UCB transplant. FT1050 modulation promotes multiple mechanisms, including increased proliferation, reduced apoptosis, and improved migration and homing [North 2007&2009; Hoggatt 2009]. Improved HSC homing is mediated by induction of CXCR4 gene expression leading to increased cell surface CXCR4. Further optimization of the UCB modulation process demonstrated that incubation with 10µM FT1050 for 2 hrs at 37C resulted in a maximal biological response of the FT1050-UCB (ProHema®). A Phase 1 trial was performed to evaluate the safety of FT1050-UCB paired with an unmanipulated UCB unit in reduced-intensity double UCBT (dUCBT) [Cutler 2013]. We observed durable, multi-lineage engraftment of FT1050-UCB with acceptable safety. Earlier neutrophil engraftment was observed relative to historical controls (median 17.5 vs. 21 days (historical control), p=0.045), coupled with preferential engraftment of the FT1050-UCB unit in 10 of 12 subjects. A Phase 2 multi-center clinical trial of FT1050-UCB in adult patients undergoing dUCBT for hematologic malignancies was then initiated. Subjects are randomized 2:1 to FT1050-UCB-containing vs. standard dUCBT after high-dose conditioning. The primary endpoint is a categorical analysis of neutrophil engraftment using a pre-specified control median. Data on the initial 11 subjects, of which 8 were randomized to receive FT1050-UCB, continue to demonstrate acceptable safety with adverse events attributed to FT1050-UCB limited primarily to common infusion-related side effects. Of the 8 FT1050-UCB subjects, 1 died prior to neutrophil engraftment, with the remaining 7 subjects engrafting at a median of 28 days vs. 31 days for the 3 control subjects. With median overall follow-up of 16.1 months, 4 of 8 subjects on the FT1050-UCB arm are alive with a median survival not reached (> 11.0 months). 1 of 3 control subjects is alive with median survival of 6.0 months. During the clinical translation process, the media used during FT1050 modulation of UCB was identified as a key variable. Standard UCB washing media, consisting of a nutrient-free saline solution of low molecular weight dextran and human serum albumin (LMD/HSA), is used clinically to stabilize fragile cells post-thaw by reducing lysis. This media was used in the Phase 1 trial and to initiate Phase 2. Early during the Phase 2 trial, we identified a novel cell-stabilizing nutrient-rich formulation (NRM), containing glucose, amino acids and other HSC-supporting nutrients that promoted full FT1050 modulation of UCB and increased cell viability. The expression of key FT1050-pathway genes was significantly higher with NRM compared to intermediate levels observed with LMD/HSA. Modulation of human CD34+ (hCD34+) cells with FT1050 in NRM led to an 8-fold increase over LMD/HSA in induced CXCR4 gene expression (20-fold total), which translated to significantly increased surface CXCR4 protein. In vivo homing models demonstrated that UCB CD34+ cells modulated with FT1050 in NRM resulted in a 2.2-fold homing increase relative to vehicle (p < 0.001) compared to a 1.6-fold increase with LMD/HSA (p = 0.002), with a significant difference between the two media conditions (p = 0.04). A xenotransplantation study in NSG mice with hCD34+ cells modulated with FT1050 in either NRM or LMD/HSA demonstrated a 2-fold increase in circulating hCD45+ cells 12-weeks post-transplant with NRM (p = 0.007; unpaired t-test). These findings supported the incorporation of NRM into the FT1050-UCB manufacturing process in order to further improve its clinical engraftment potential. Enrollment of a 60-patient Phase 2 trial has been initiated that incorporates this manufacturing change. Disclosures Shoemaker: Fate Therapeutics: Employment, Equity Ownership. Rezner:Fate Therapeutics: Employment. Guerrettaz:Fate Therapeutics: Employment. Robbins:Fate Therapeutics: Employment. Medcalf:Fate Therapeutics: Employment. Wolchko:Fate Therapeutics: Employment, Equity Ownership. Ferraro:Fate Therapeutics: Employment. Multani:Fate Therapeutics: Employment.