Comparative analysis of tabelecleucel and current treatment in patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease following hematopoietic cell transplant or solid organ transplant.

AIMS: With recent European Union marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy approved for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). In the absence of a control arm, real-world evidence can provide a comparative benchmark for single-arm studies in ultra-rare populations. This study assessed the treatment effect of tabelecleucel in the single-arm phase 3 ALLELE study (NCT03394365) versus a treatment group from a multinational, multicenter retrospective chart review study (RS002) of patients with EBV+ PTLD. METHODS: In ALLELE, patients had disease relapsed/refractory to rituximab ± chemotherapy and received tabelecleucel 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Patients in RS002 had disease relapsed/refractory to rituximab ± chemotherapy and received next line of systemic therapy between January 2000 and December 2018. Propensity score-based standardized mortality/morbidity ratio weighting was used to achieve balance between treatment and comparator arms. Kaplan-Meier estimators and Cox regression models were used to compare overall survival (OS) in the re-weighted sample. RESULTS: 30 patients (n = 14 hematopoietic cell transplant [HCT], n = 16 solid organ transplant [SOT]) from ALLELE (data cutoff: November 2021) and 84 patients (n = 36 HCT, n = 48 SOT) from RS002 (data lock: January 2021) were included. Median time from diagnosis to first tabelecleucel dose (ALLELE) or start date of next line of systemic therapy (RS002) was 3.6 months. Tabelecleucel was associated with a substantial OS benefit compared with current treatment, with an unadjusted HR of 0.47 (95% confidence interval [CI] 0.25-0.88) and adjusted HR of 0.37 (95% CI 0.20-0.71) when using the start date of the next line of therapy as the index date. Sensitivity analyses yielded consistent results. CONCLUSIONS: In this study of real-world data, tabelecleucel was associated with an OS benefit among patients with R/R EBV+ PTLD for whom there is high unmet need.

Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy.

Epstein-Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV+ PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV+ PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV+ PTLD following HCT to describe patients' demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV+ PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population.

Treatment Patterns and Unmet Need for Patients with Progressive Multiple Sclerosis in the United States: Survey Results from 2016 to 2021.

INTRODUCTION: Much of the current literature on treatment patterns and disability progression in multiple sclerosis (MS) does not distinguish between the relapsing-remitting and progressive subtypes (including primary [PPMS] and secondary progressive MS [SPMS]), or between active/nonactive disease. Current treatment options for progressive MS are limited, with only one approved product for PPMS and none specifically for nonactive SPMS. Here we report treatment patterns, disability progression, and unmet needs among patients with active and nonactive PPMS and SPMS. METHODS: The annual, cross-sectional survey from the Adelphi Disease Specific Program was used to collect physician-reported data on US adult patients with PPMS and SPMS, including active and nonactive disease. Treatment patterns (including the proportion of patients who were untreated with a disease-modifying therapy [DMT]), disability progression, and unmet need are described from 2016 to 2021. RESULTS: Data were collected for 2067 patients with progressive MS (PPMS, 1583; SPMS, 484). A substantial proportion of patients were untreated across all groups, and this was highest for nonactive PPMS (~ 43%). The proportion of untreated patients generally declined over time but remained high in 2018-2021 (~ 10-38%). Among treated patients, the proportion receiving infusions increased over time to ~ 34-46%, largely driven by ocrelizumab use after approval. Disability progression was reported for most patients (> 50%), including many who were receiving a DMT. Across all disease subtypes, when physicians were asked about the greatest unmet need with current DMTs, they most frequently cited effectiveness (~ 63-87%), and specifically slowing disease progression (~ 32-59%). CONCLUSIONS: This analysis of physician-reported data reveals that patients with progressive MS, particularly those with nonactive disease, frequently remain untreated or continue to decline despite treatment with available DMTs. Thus there is an enduring need for safe and effective treatments for this underserved population.

Expert Consensus on the Characteristics of Patients with Epstein-Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) for Whom Standard-Dose Chemotherapy May be Inappropriate: A Modified Delphi Study.

INTRODUCTION: Following hematopoietic stem cell transplantation or solid organ transplantation, patients are at risk of developing Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD), which is an ultra-rare and potentially lethal hematologic malignancy. Common treatments for EBV+ PTLD include rituximab alone or combined with chemotherapy. Given specific considerations for this population, including severity of the underlying condition requiring transplant, the rigors of the transplant procedure, as well as risks to the transplanted organ, there is a group of patients with EBV+ PTLD for whom chemotherapy may be inappropriate; however, there is limited information characterizing these patients. This study aimed to reach expert consensus on the key characteristics of patients for whom chemotherapy may be inappropriate in a real-world setting. METHODS: A two-round modified Delphi study was conducted to reach consensus among clinicians with expertise treating EBV+ PTLD. Articles identified in a targeted literature review guided the development of round 1 and 2 topics and related statements. The consensus threshold for round 1 statements was 75.0%. If consensus was achieved in round 1, the statement was not discussed further in round 2. The consensus thresholds for round 2 were moderate (62.5-75.0%), strong (87.5%), or complete (100.0%). RESULTS: The panel was composed of a total of eight clinicians (seven hematologists/hemato-oncologists) from six European countries. The panel generated a final list of 43 consensus recommendations on the following topics: terminology used to describe patients for whom chemotherapy may be inappropriate; demographic characteristics; organ transplant characteristics; comorbidities that preclude the use of chemotherapy; EBV+ PTLD characteristics; and factors related to treatment-related mortality and morbidity. CONCLUSIONS: This modified Delphi panel successfully achieved consensus on key topics and statements that characterized patients with EBV+ PTLD for whom chemotherapy may be inappropriate. These recommendations will inform clinicians and aid in the treatment of EBV+ PTLD.

A review of the risks of long-term consequences associated with components of the CHOP chemotherapy regimen.

A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the CHOP regimen. Long-term consequences for CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8-fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed.

Results from Patient Interviews on Fatigue in Progressive Multiple Sclerosis and Evaluation of Fatigue Patient-Reported Outcome (PRO) Instruments.

INTRODUCTION: Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS) but is challenging to assess and has not been comprehensively characterized in patients with progressive MS. This study aimed to (1) obtain qualitative evidence from patients with progressive MS to characterize MS-related fatigue concepts and their impacts on health-related quality of life (HRQoL), and (2) evaluate the conceptual frameworks of existing MS-specific fatigue patient-reported outcome (PRO) instruments using study data to determine the most suitable PRO instrument in this population. METHODS: Qualitative interviews were conducted with 30 US participants with confirmed progressive MS and fatigue in the last 6 months to assess their MS-related fatigue. Data were compared with concepts in existing PRO instruments to evaluate their relevance in progressive MS. RESULTS: Physical and mental concepts of fatigue were identified and characterized distinctly from patients with progressive MS. Most patients characterized fatigue as occurring daily and lasting several hours, with negative impacts on HRQoL. Concept mapping to existing MS-specific fatigue PRO instruments supported the Fatigue Severity Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) as the most suitable existing option for assessing fatigue in patients with progressive MS, as it separates physical and mental aspects of fatigue and includes every highly endorsed concept reported by the interviewed patients. CONCLUSIONS: This qualitative study identified meaningful physical and mental fatigue concepts in patients with progressive MS and preliminarily supports the use of the FSIQ-RMS for this population. More research is needed to fully validate this instrument for progressive MS.

Mean lifetime survival estimates following solid organ transplantation in the US and UK.

AIMS: Accurately estimating mean survival after solid organ transplant (SOT) is crucial for efficient healthcare resource allocation decisions. However, registry-based post-transplant recipient survival estimates vary greatly and are incomplete. Often, the methods used in lifetime survival extrapolation may not fit complex transplant data and therefore alternative methods are required. We aimed to explore the flexible cubic spline methodology as a meaningful alternative for estimating lifetime survival following SOT. METHODS: Survival analyses were conducted in kidney, liver, heart, and lung transplant recipients. Mean survival was estimated using flexible cubic splines on the hazard scale fitted with three knots, based on where hazards changed direction, clinical advice, and best-fit curve using Akaike and Bayesian information criterion. The tail was extrapolated when data were no longer available. Extrapolation tails were compared with general population mortality, using age-matched life table hazards, and the highest hazards were taken at all times. RESULTS: We found that mean survival post-transplant was longest for kidney transplants (US: 22.79 years; UK: 26.58 years), followed by liver (US: 20.90 years; UK: 20.38 years), heart (US: 14.82 years; UK: 15.85 years), and lung (US: 9.28 years; UK: 9.21 years). A sensitivity analysis using two knots found differences in survival ranging from -1.30 to +4.83 years across SOTs examined. LIMITATIONS: This study does not represent individual patient survival, survival by age groups, multiple-organ transplants, or assess factors that may impact overall or organ survival. CONCLUSIONS: Our study estimates reflect real-world survival following SOTs and demonstrate the importance of including long-term hazards in survival estimations. These lifetime survival estimates can be used by decision-makers in situations where means are preferred over medians (e.g. population projections, budgetary estimates, and cost-effectiveness models) and can thus offer a meaningful alternative to the estimates used and accepted in current practice.

Cost burden of post-transplant lymphoproliferative disease following kidney transplants in Medicare-eligible patients by survival status.

AIMS AND OBJECTIVES: Patients diagnosed with post-transplant lymphoproliferative disease (PTLD) experience high mortality within the first 2 years of diagnosis; however, few data exist on the economic burden of PTLD in these patients. We determined the healthcare resource utilization (HRU) and cost burden of post-kidney transplant PTLD and evaluated how these differ by survival status. MATERIALS AND METHODS: Utilizing data from the United States Renal Data System and the Scientific Registry of Transplant Recipients, we identified 83,818 Medicare-covered kidney transplant recipients between 2007 and 2016, of which 347 had at least one Medicare claim during the first year after diagnosis of PTLD. We tabulated Medicare Part A and Part B and calculated per patient-year (PPY) costs. RESULTS: Patients diagnosed with PTLD in the first year post-transplant had Part A + B costs of $222,336 PPY, in contrast with $83,546 PPY in all kidney transplants. Post-transplant costs in the first year of PTLD diagnosis were similar regardless of the year of diagnosis. Cost burden for PTLD patients who died within 2 years of diagnosis was >3.3 times higher than PTLD patients still alive after 2 years. Of those who died within 2 years, the majority died within 6 months and costs were highest for these patients, with almost 7 times higher costs than PTLD patients who were still alive after 2 years. LIMITATIONS: Medicare costs were the only costs examined in this study and may not be representative of other costs incurred, nor be generalizable to other insured populations. Patients were only Medicare eligible for 3 years after transplant unless aged ≥62 years, therefore any costs after this cut-off were not included. CONCLUSIONS: PTLD represents a considerable HRU and cost burden following kidney transplant, and the burden is most pronounced in patients who die within 6 months.

Qualitative Findings on the Impact of Disease in Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease Patients, as Measured by EQ-5D, SF-36, and the FACT-LYM.

INTRODUCTION: There are no validated patient-reported outcome (PRO) instruments for Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD). The aim of this study was to assess the content applicability for three frequently used PRO instruments from the perspective of patients with EBV+ PTLD. METHODS: A moderated focus group comprising adult patients with EBV+ PTLD was conducted using a concept confirmation and an open-ended concept elicitation approach. The domains of the EuroQoL Group-5 Dimension (EQ-5D) instrument, Short Form Health Survey-Version 2 (SF-36v2) questionnaire, and Functional Assessment of Chronic Illness Therapy-Lymphoma (FACT-LYM) questionnaire were discussed. The concept elicitation portion was a general discussion of symptoms and patient burden of EBV+ PTLD. RESULTS: Six patients participated in this study: five women and one man. Most participants reported acute pain in the location of their EBV+ PTLD. All participants reported significant physical fatigue and experienced productivity loss. Patients reported emotional fatigue, feelings of dissociation, lack of motivation, and persistent fear of disease progression, including mortality. Patients described their social functioning as disjointed, behaving differently with loved ones/caregivers than when alone. The EQ-5D was relevant for the pain/discomfort and anxiety/depression domains; most SF-36v2 domains were relevant, with the exception of the general health perception domain, which was not applicable; all domains in the FACT-LYM were relevant. The open-ended portion drew no new content. CONCLUSIONS: This qualitative research identified meaningful concepts in patients with EBV+ PTLD, with physical, emotional, and social functioning being impacted. The FACT-LYM questionnaire was the most relevant of the three PROs studied, with all domains relevant to this population. It is important to properly analyze PRO data in patients with EBV+ PTLD.

Retrospective database analysis of healthcare resource utilization and costs in patients who develop post-transplant lymphoproliferative disease within the first year following allogeneic hematopoietic stem cell transplants.

AIMS: Healthcare resource utilization (HRU) and costs in post-transplant lymphoproliferative disease (PTLD) patients following allogeneic hematopoietic stem cell transplant (HCT) were evaluated in the USA. METHODS: MarketScan Commercial and Medicare Supplemental database claims from 01 July 2010 to 31 December 2017 were analyzed. Patients eligible for analysis received allogeneic HCT between 01 January 2011 to 31 December 2015, had ≥6 months of continuous enrollment before HCT, and had ≥1 claim for PTLD or ≥1 inpatient or ≥2 outpatient claims for a clinically-relevant lymphoma within 1 year following HCT (PTLD index = first claim of diagnosis). Patients with clinically-relevant lymphomas within 6 months before HCT were excluded. HRU and total paid amounts were assessed from the week before the HCT through 1-day pre-PTLD index (HCT to PTLD) and monthly from PTLD index through 1-year post-PTLD index. HRU is reported as mean (SD). Results were also provided by survival status. RESULTS: Overall, 92 patients were eligible for analysis. From HCT to PTLD, 98.9% of patients were hospitalized, with 1.7 (1.2) hospitalizations/patient. The average length of stay was 25.3 (22.2) days/patient. From HCT to PTLD, 98.9% of patients had outpatient services with 233.7 (261.1) services/patient and 91.3% of patients had a prescription fill with 32.9 (26.0) prescriptions/patient. In the first month post-PTLD index, 51.2% of patients were hospitalized. Mean paid amounts were $399,470/patient (range $7542-$1.7 M) from HCT to PTLD. Cumulative mean paid amounts 1-year post-PTLD were $429,043/patient. Total cost/patient/month was ∼7 times higher in patients who died (n = 49; $232,591) than those who lived (n = 43; $33,677). Costs were mainly driven by hospitalizations. LIMITATIONS: Limitations include those inherent to retrospective analyses (i.e. miscoding, lack of clinical detail). CONCLUSIONS: HRU and costs from HCT to PTLD were high and more than doubled within 1-year post-PTLD. PTLD patients who died had ∼7 times higher costs than those who lived, driven by hospitalizations. Effective treatments are needed to reduce the burden of PTLD.

Exploring the burden of short-term CHOP chemotherapy adverse events in post-transplant lymphoproliferative disease: a comprehensive literature review in lymphoma patients.

PURPOSE: Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients. DESIGN: This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies. RESULTS: PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations. CONCLUSIONS: Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.

Clinician Concepts of Cure in Adult Relapsed and Refractory Philadelphia-Negative B Cell Precursor Acute Lymphoblastic Leukemia: A Delphi Study.

INTRODUCTION: Despite the poor prognosis for adults with relapsed or refractory (RR) Philadelphia chromosome (Ph)-negative B cell precursor acute lymphoblastic leukemia (ALL), long-term survival is possible and may even be considered as "cure". METHODS: This study used a Delphi panel approach to explore concepts of cure in RR Ph-negative B cell precursor ALL. Ten European experts in this disease area participated in a survey and face-to-face panel meeting. RESULTS: Findings showed that clinicians conceptualize "cure" as a combination of three broad treatment outcomes that vary depending on the treatment stage: complete remission early in treatment (1-3 months) indicates initial success; eradicating cancer cells (minimal residual disease negative status) consolidates the early clinical response; leukemia-free survival is required in the long term. CONCLUSIONS: Although such terminology remains contested, clinicians would begin considering "cure" as early as 2 years provided the patient is off therapy, with most considering the term applicable by the third year. FUNDING: Amgen Inc.

Correction to: Number-needed-to-treat analysis of clinical progression in patients with metastatic castration-resistant prostate cancer in the STRIVE and TERRAIN trials.

It has been highlighted that in the original article [1] there was a typesetting mistake in the Results - NNT in Strive section. This Correction article states the incorrect and correct sentence.

Number-needed-to-treat analysis of clinical progression in patients with metastatic castration-resistant prostate cancer in the STRIVE and TERRAIN trials.

BACKGROUND: This analysis estimated the number needed to treat with enzalutamide versus bicalutamide to achieve one additional patient with chemotherapy-naïve metastatic castration-resistant prostate cancer who would obtain clinical benefit regarding progression-free survival, radiographic progression-free survival, or no prostate-specific antigen progression at 1 and 2 years following treatment initiation. METHODS: Clinical event rates were obtained from the STRIVE (NCT01664923) and TERRAIN (NCT01288911) trials, and the number needed to treat was the inverse of the absolute rate difference between the event rates of enzalutamide and bicalutamide. The 95% Confidence Interval of the number needed to treat was derived from the 95% Confidence Interval of the event rate difference. RESULTS: Using STRIVE data (patients with metastatic disease: n = 128 enzalutamide; n = 129 bicalutamide) comparing enzalutamide with bicalutamide at 1 and 2 years, the numbers needed to treat to achieve one additional patient with chemotherapy-naïve metastatic castration-resistant prostate cancer with progression-free survival were 2.0 and 2.8, respectively; with radiographic progression-free survival, 2.6 and 3.0, respectively; and without prostate-specific antigen progression, 1.8 and 2.4, respectively. Using TERRAIN data (n = 184 enzalutamide; n = 191 bicalutamide) comparing enzalutamide with bicalutamide at 1 and 2 years, the numbers needed to treat to achieve one additional patient with progression-free survival were 4.3 and 3.7, respectively; with radiographic progression-free survival, 10.0 and 2.8, respectively; and without prostate-specific antigen progression, 2.1 and 3.2, respectively. CONCLUSIONS: The combined data from TERRAIN and STRIVE demonstrated that treating chemotherapy-naïve metastatic castration-resistant prostate cancer with enzalutamide leads to more patients without clinical progression at 1 and 2 years than with bicalutamide. TRIAL REGISTRATION: STRIVE (NCT01664923; registration date: August 10, 2012) and TERRAIN (NCT01288911; registration date: February 1, 2011).

Correction to: Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S. Real-World Analysis Using the SEER-Medicare Database.

The original article can be found online.

Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S. Real-World Analysis Using the SEER-Medicare Database.

INTRODUCTION: Bicalutamide (BIC), a non-steroidal anti-androgen, is FDA-indicated for use in combination with a luteinizing hormone-releasing hormone (LHRH) analog for treatment of Stage D2 metastatic carcinoma of the prostate. Lack of consensus exists regarding the clinical benefit of BIC use, either alone or combined use of BIC with an LHRH analog or antagonist (combined androgen blockade or CAB), versus treatment with androgen deprivation therapy (ADT) alone. METHODS: The SEER-Medicare database was used to identify prostate cancer patients aged ≥ 66 years diagnosed between 2007 and 2011 and who filled at least one prescription for BIC. Duration of BIC treatment was assessed in relation to ADT use; either alone (monotherapy), as part of CAB only, and as part of CAB followed by monotherapy. Additionally, we assessed use of BIC during or outside a potential testosterone flare prevention period (initiation within 2 months of an LHRH agonist). RESULTS: A total of 7521 prostate cancer patients who filled a prescription for BIC were identified. Eighteen percent of the cohort used BIC alone, over half the patients (54%) used BIC as part of CAB and 27% used BIC as part of CAB followed by monotherapy. Among men treated with BIC as part of CAB, 58% received BIC only within the potential flare period. CONCLUSIONS: Although there is no FDA indication for BIC use as monotherapy, > 44% of patients in this study used BIC alone or as part of CAB followed by monotherapy. Further research is necessary to understand the outcomes of BIC utilization in these settings, particularly compared with newer second-generation anti-androgens. FUNDING: Medivation LLC, a Pfizer company, and Astellas, Pharma, Inc.

Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States.

BACKGROUND: The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease. RESULTS: There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease. CONCLUSIONS: Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018;124:2104-14. © 2018 American Cancer Society.

Number needed to treat and associated incremental costs of treatment with enzalutamide versus abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: Enzalutamide (ENZA) and abiraterone acetate plus prednisone (AA) are approved second-generation hormone therapies for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). This study compared ENZA with AA in chemotherapy-naïve mCRPC by calculating the number needed to treat (NNT) and associated incremental costs to achieve one additional chemotherapy-naïve patient with mCRPC free of radiographic progression, chemotherapy, or death over a 1-year time horizon. METHODS: Clinical outcomes were obtained from the PREVAIL and COU-AA-302 trials. Three outcomes were evaluated: radiographic progression-free survival, time to cytotoxic chemotherapy initiation, and overall survival at 1 year. NNT was calculated as the reciprocal of the outcome event rate difference for ENZA compared with AA. The incremental costs to achieve one additional outcome at 1 year were calculated as the difference in cost per treated patient multiplied by the NNT. Per-treated-patient costs were considered from a US payer perspective and included medications, monitoring, adverse events, post-progression treatments, and end-of-life care. RESULTS: Within a 1-year time horizon, the total cost per treated patient for ENZA was $2,666 less than AA. Compared with AA, treating 14 patients with ENZA resulted in one additional patient free of progression or death over 1 year; treating 26 patients with ENZA resulted in one additional patient with chemotherapy delayed over 1 year; and treating 91 patients with ENZA resulted in one additional patient free of death over 1 year. Therefore, ENZA is cost-effective compared with AA for all three outcomes evaluated, and the modeled results suggest ENZA is associated with potentially improved clinical outcomes in delaying chemotherapy initiation and disease progression for chemotherapy-naïve patients. The results are robust in sensitivity analyses, where the effect of changes in key model inputs and assumptions were tested. CONCLUSION: The results modeled in the present study suggest ENZA is cost-effective compared with AA for treating chemotherapy-naïve patients with mCRPC.

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data.

INTRODUCTION: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years. METHODS: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population. RESULTS: At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results. CONCLUSIONS: These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(-) B-precursor ALL compared with salvage chemotherapy. FUNDING: Amgen. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

Healthcare burden and reimbursement of hospitalization during chemotherapy for adults with Ph-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in France: a retrospective chart review.

OBJECTIVE: Philadelphia chromosome negative [Ph(-)] relapsed or refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) is an extremely rare condition requiring intensive treatment. This retrospective chart review aimed to quantify hospitalizations and reimbursement in this patient population in France. METHODS: Patients aged ≥18 years and with at least one hospitalization for Ph(-) R/R B-precursor ALL were included in the study. They were relapsed with first remission lasting <12 months, relapsed after first salvage therapy, relapsed any time after hematopoietic stem cell transplant (HSCT), or were refractory to initial or salvage therapy. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up. The chemotherapy period was defined as the first chemotherapy date after the index date to the earliest of death, loss to follow-up, last chemotherapy dose plus 30 days, or initiation of HSCT. The primary outcome was the percentage of time hospitalized during the chemotherapy period. RESULTS: Thirty-three patients were included, with a mean age of 49 years. The mean proportion of time spent in the hospital during the chemotherapy period was 46% (95% CI =34-57%). Patients had a mean of 2.2 (SD =1.5) inpatient hospitalizations and the mean length of stay per hospitalization was 16.8 (SD =14.8) days. During the chemotherapy period, the mean amount reimbursed per hospitalization was €31 067 (SD = €4850) and the total hospitalization reimbursement per patient was €68 344. From the index date to death, excluding HSCT, the total reimbursement per patient was €108 873. LIMITATIONS: The sample size was small, although this was expected given the rarity of the patient population. CONCLUSIONS: Adults with Ph(-) R/R B-precursor ALL had repeated and prolonged hospitalizations during salvage chemotherapy. Approximately half the follow-up period was spent in the hospital, and this time was associated with high economic burden in France.