scholarly journals Impact of Novel Treatments on Multiple Myeloma Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5676-5676 ◽  
Author(s):  
David Robinson ◽  
Satyin Kaura ◽  
Daniel Kiely ◽  
Mohamad A. Hussein ◽  
Knar Nersesyan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Survival ◽  
Cohort Analysis ◽  
Survival Rates ◽  
Relative Survival ◽  
Clinical Trial Data ◽  
Novel Therapies ◽  
Employment Equity ◽  
Equity Ownership ◽  
The Impact

Abstract BACKGROUND: Multiple myeloma survival has significantly improved with the introduction of new therapeutic classes in the early 2000s. The magnitude of improvement in survival with better tolerated therapy is essentially transforming the disease from an acute condition, to a potentially manageable chronic disease . The impact of further advances in multiple myeloma therapy is not yet known but can be projected based on analysis of historical data and positive outcomes that are expected for future clinical trials. METHODOLOGY: Analysis of data from the Surveillance, Epidemiology and End Results (SEER) were performed using SEERStat software. The first part of this analysis compares the median relative survival, based on cohort analysis, and five year relative survival, based on period analysis, for different time periods that coincided with the introduction of newer, better tolerated, more effective therapies for treating multiple myeloma. The second part of this analysis attempts to estimate future changes in survival, that may potentially result from additional disease modifying therapies planned to become available over the next 5-10 years. This will be accomplished through analysis of evidence-based metrics including extrapolation from early phase clinical trial data and validation with key opinion leaders. RESULTS: Median, cumulative and 5 year relative survival of multiple myeloma have improved over the last decade primarily as a result of the introduction of newer therapies such as thalidomide, lenalidomide and bortezomib. Based on analysis of SEER data, median relative survival from the 1980s to 2000 showed modest changes, averaging approximately 30 months through the two decades. Thereafter, median survival increased to nearly 50 months by 2007 (FIGURE 1). Five year relative survival improved from about 30% in 1990 to over 46% in 2010 (FIGURE 2). SUMMARY: This analysis highlights the dramatic improvements in multiple myeloma survival over the last three decades in the U.S., and demonstrates the transformative impact and value of novel therapies for multiple myeloma. The most substantial improvements were observed during the period between 2001 and 2007, when multiple myeloma median survival rates increased by 45%. This improvement has predominantly been driven by the introduction of novel classes of drugs and agents, including immunomodulatory and proteasome inhibitors. Over the next 10 years we expect to see a similar trend, where further advances in the treatment of multiple myeloma will yield additional novel therapies that could result in improvements of comparable or better magnitude. FIGURE 1 FIGURE 1. FIGURE 2 FIGURE 2. Disclosures Kaura: Celgene: Employment, Equity Ownership. Kiely:Celgene: Employment, Equity Ownership. Hussein:Celgene: Employment, Equity Ownership. Durie:Celgene: Advisory Board Celgene, IRC Onyx, DMC Millennium, IRC J&J Other.

scholarly journals Could Patients with Multiple Myeloma (MM) Derive Additional Benefit from Their Treatments? Real-World Evidence for Carfilzomib Dosing Intensity on Survival and Treatment Progression

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 836-836 ◽  
Author(s):  
Rohan Medhekar ◽  
Dionne Hines ◽  
Sumeet Panjabi ◽  
Tim Welliver ◽  
Xin Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Lower Risk ◽  
Index Date ◽  
Cox Model ◽  
Weekly Dose ◽  
Employment Equity ◽  
K Index ◽  
Equity Ownership ◽  
The Impact

Abstract Introduction: Carfilzomib (K) was first approved in 2012 for the treatment of relapsed/refractory multiple myeloma (RRMM) at a dose of 27 mg/m2 twice weekly (27 BIW). The K dose has since been optimized; carfilzomib plus dexamethasone (Kd) is approved for patients with RRMM at a recommended K dose of 56 mg/m2 twice weekly (56 BIW) since 2016. Recently, the A.R.R.O.W trial showed that Kd 70mg/m2 once weekly (70 QW) significantly improved progression free survival compared to Kd 27 BIW. Considering the study time-period, however, patients are still treated with 27 BIW in the real-world leaving them possibly under-treated. The Kd 27 BIW, corresponds to a cumulative weekly dose (CWD) of K <120mg, while both Kd 56 BIW and Kd 70 QW (optimized dose-56 BIW/70 QW) correspond to a CWD of K >120mg. Therefore, in order to understand the relationship between dose and outcomes we examined the impact of K-dosing (CWD >120mg [optimized dose-56 BIW/70 QW] vs. CWD ≤120 mg [27 BIW]) on time to next treatment (TTNT) and overall survival (OS) among patients treated with Kd regimen. Methods: IQVIA's Oncology Electronic Medical Records database was used to identify patients ≥18 years of age, with a diagnosis of MM between 1/1/2010 and 10/31/2017, receiving Kd regimen in any line of therapy, with ≥ 3 doses of K on or after their K-index date (first administration of K in the Kd regimen, between 1/1/2013 and 10/31/2017). Patients were required to have ≥ 3 doses of K in order to establish continuity and for calculating CWD. CWD was calculated as the cumulative sum of weekly dose of K received by the patient divided by the number of weeks with Kd administration. The first two K doses were excluded from the calculation of CWD as these represent the loading dose. OS and TTNT were compared between patients receiving optimized dose-56 BIW/70 QW vs. 27 BIW. OS was evaluated among the subset of patients with a recorded deceased or alive status and measured from the K-index date until death due to any cause or the end of the study period, where they were censored. TTNT was defined as the time from initiation of the Kd regimen until the start of a subsequent regimen that did not contain Kd (treatment progression). Additionally, a landmark analysis at 12 months from initiation of Kd regimen was conducted to measure the proportion of patients alive and the proportion of patients with treatment progression. Kaplan-Meier analysis was used to estimate OS and TTNT and the log-rank test was used to compare the groups. Adjusted hazard ratios for OS and TTNT were evaluated using Cox models. Results : A total of 1,469 eligible MM patients with ≥3 Kd administrations were identified, of which 129 (8.8%; mean age: 63.5, SD: 9.8) received optimized dose-56 BIW/70 QW and 1,340 (91.2%; mean age: 67.0, SD: 10.4) received 27 BIW. The median follow-up time was slightly over a year for patients in both cohorts. The median K dose was 147.0 mg among patients in optimized dose-56 BIW/70 QW group and 88.1 mg among patients in 27 BIW group. Median OS was not estimable (NE), however, OS for the optimized dose-56 BIW/70 QW group (n=78) was significantly longer than that of the 27 BIW group (n=771; p=0.002) (Fig. 1). The proportion of patients in optimized dose-56 BIW/70 QW group alive at 12 months was 90.3% compared to 79.7% for patients in 27 BIW group respectively. Covariate-adjusted cox model showed that patients in optimized dose-56 BIW/70 QW group had a 64% lower risk of death than patients in 27 BIW group (adjusted HR: 0.364; 95% CI: 0.178-0.745; p = 0.0057, Table 1). TTNT was significantly longer for patients in optimized dose-56 BIW/70 QW group compared to patients in 27 BIW group (p=0.023; median TTNT: 17.5 [95% CI: 14.8-NE] and 13.2, [95% CI: 12.4-14.4], respectively) (Fig. 2). Covariate-adjusted cox model showed that patients in optimized dose-56 BIW/70 QW group had a 33% lower risk of treatment progression than patients in 27 BIW group (adjusted HR: 0.669; 95% CI: 0.483-0.927; p=0.0155, Table 1). Conclusion: Among patients treated with Kd regimen, a smaller proportion were prescribed K at optimized dose-56 BIW/70 QW. Patients receiving the optimized dose-56 BIW/70 QW had significantly improved OS and TTNT compared to those receiving 27 BIW. Our findings suggest that these patient-relevant outcomes may be improved in a vast majority of RRMM patients currently under-treated with carfilzomib by optimizing the dose, taking into consideration patients' comorbidities and ability to tolerate therapy. Disclosures Medhekar: Amgen: Employment, Equity Ownership. Hines:Amgen: Consultancy. Panjabi:Amgen: Employment, Equity Ownership. Welliver:Amgen: Employment, Equity Ownership. Wang:Amgen: Consultancy. Wade:Amgen: Consultancy.

scholarly journals Carfilzomib Dosing Patterns and Survival in Patients with Relapsed and Refractory Multiple Myeloma: An Analysis from US Community Oncology Practices

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2084-2084
Author(s):  
Robert M. Rifkin ◽  
Eileen Fonseca ◽  
Yaozhu J. Chen ◽  
Patricia S. Fox ◽  
James E. Browning ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Employment Equity ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Community Oncology ◽  
Social Security Death Index ◽  
Equity Ownership ◽  
The Impact ◽  
Dosing Patterns

Abstract Introduction While novel agents have improved survival over the last decade, multiple myeloma (MM) remains incurable. Carfilzomib (CFZ), a second-generation proteasome inhibitor, was approved in July 2012 by the US Food and Drug Administration and had a label change in July 2015. During this study's data period, the label recommended Cycle 1 dose at 20 mg/m2/day and if tolerated increase Cycle 2 dose and subsequent cycles doses to 27 mg/m2/day. The purpose of this study is to assess baseline characteristics, CFZ dosing patterns and survival among MM patients in a US community oncology setting. Methods A retrospective study of MM patients from US Oncology Network practices that fully implemented McKesson Specialty Health's iKnowMed (iKM) oncology-specific electronic health records database was conducted on patients whose first treatment of CFZ (index) occurred between Jul-2012 and Nov-2014. Patients were eligible if they had a documented initial MM diagnosis date and had their first CFZ cycle documented in the database. Additionally, patients were required, before Dec-2014, to have either another visit to the practice post-index or a record of death and not have participated in interventional clinical trials during the previous 6 years. Data on eligible patients were collected up to March 2015. The death event was defined by the Social Security Death Index, supplemented by iKM; patients without the event were censored at the date of last observed visit. To adjust for clinical practice variations, a 10% variability was allowed for the recommended daily dose levels of 20 mg/m2 and 27 mg/m2. A subgroup was defined for patients with a 2nd cycle: "escalators" if they received 20 mg/m2/day doses throughout Cycle 1 and increased to 27 mg/m2/day on the first dose of Cycle 2; "non-escalators" if they received only 20 mg/m2 doses throughout Cycle 1 and did not increase to 27 mg/m2 on the first dose of Cycle 2; receiving any dose not equal to 20 or 27 mg/m2 were classified into "other". Survival after index was estimated using the Kaplan-Meier method with 95% confidence intervals (CI). A multivariable Cox proportional hazards (PH) model was conducted to evaluate the impact of escalation on survival accounting for selected baseline demographic and clinical characteristics. Results The cohort of 718 CFZ patients were identified with a median (interquartile range [IQR]) age of 68 (61-75) years at index, 57% (n=409) were male, and 12% (n=87) were Black and 77% (n=551) were Caucasian. At initial MM diagnosis, 19%, 27% and 42% were ISS Stage I, II, and III, respectively. Median (IQR) time from MM diagnosis to index was 3.6 (1.9-5.8) years. At index, 66% of patients had an ECOG performance status of 0-1, 21% of 2, and 2% of 3+; 54% (n=369) had moderate to severe renal impairment (eGFR<60 mL/min per 1.73 m2). Ninety percent (n=644) of patients started CFZ at 20 mg/m2, 4% (n=27) at 27 mg/m2 and 4% (n=25) at 15 mg/m2. Patients had a median (IQR) of 4 (2-7) cycles of CFZ and 45% (n=321) escalated to ≥27 mg/m2. Among these 321 patients, median (IQR) time to first escalation was 30 (28-56) days with 60% escalating in Cycle 2. The subgroup defined in "Methods" included 605 patients: 148 (24%) escalators, 342 (57%) non-escalators, and 115 (19%) other. Median (95% CI) duration from index to death was 21 (17.5-23.2) months. Unadjusted overall survival (OS) was significantly lower among non-escalators compared to escalators (log-rank p=0.024) [Figure 1]. Survival rates (95% CI) for non-escalators and escalators were 68% (62-74%) and 75% (66-82%) at year 1 and 42% (33-50%) and 61% (49-71%) at year 2, respectively. Within the multivariable Cox model, escalators showed a 33% significantly lower risk of death compared to non-escalators (HR=0.67, p=0.03) while also accounting for race, sex, age group, renal function per EGFR, and MM chain type. Other significant variables in this model were: EGFR < 15 and 15-29 vs 30-59 ml/min per 1.73m2 (HR=2.79, p<0.01; HR=1.64, p=0.04, respectively) and lambda vs kappa light chain (HR=1.55, p=0.03). Conclusions These results indicate escalation of CFZ at first dose of Cycle 2 is associated with better survival than dosing at 20 mg/m2 in Cycle 1 but not escalating at the start of Cycle 2. More research is needed to assess factors that impact physician decision-making on dose escalation to better inform physicians to improve the quality of multiple myeloma care. Disclosures Rifkin: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fonseca:McKesson Specialty Health, which received funding to conduct this research: Employment, Equity Ownership. Chen:Onyx Pharmaceuticals: Employment. Fox:McKesson Specialty Health, which received funding to conduct this research: Employment. Browning:Onyx Pharmaceuticals, An Amgen Subsidiary: Employment. Cong:Onyx Pharmaceuticals: Employment, Equity Ownership.

Safety and Efficacy of Venetoclax (ABT-199/GDC-0199) Monotherapy for Relapsed/Refractory Multiple Myeloma: Phase 1 Preliminary Results

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4219-4219 ◽  
Author(s):  
Shaji K. Kumar ◽  
Ravi Vij ◽  
Jonathan L. Kaufman ◽  
Joseph R. Mikhael ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Abdominal Pain ◽  
Research Funding ◽  
Phase 1 ◽  
Cell Transplant ◽  
Brain Hemorrhage ◽  
Employment Equity ◽  
Equity Ownership ◽  
Upper Abdominal ◽  
The Impact

Abstract Background: The anti-apoptotic protein BCL-2 has been implicated in mediating the survival of multiple myeloma (MM) cells. Venetoclax is a potent, selective, orally bioavailable small-molecule BCL-2 inhibitor. Venetoclax induces cell death in MM cell lines in vitro and primary MM samples ex vivo. Certain genetic subtypes of MM cells are particularly sensitive to venetoclax, including t(11;14) cells, which express a high ratio of BCL2 to MCL1 (venetoclax resistance factor). The current Phase 1 study evaluates safety, efficacy, and pharmacokinetics (PK) in patients (pts) with relapsed/refractory MM. Methods: Primary objectives are to evaluate safety, PK, and recommended phase two dose; other objectives include assessing preliminary efficacy and the impact of chromosomal abnormalities. In dose-escalation (DE) cohorts, venetoclax was given orally daily at 300, 600, 900, or 1200 mg after a 2-week dose ramp-up (3+3 design). Patients in the safety expansion (SE) cohort received 1200 mg daily after ramp-up. All patients were monitored for tumor lysis syndrome (TLS). Results: As of June 17, 2015, 37 patients were enrolled in the study: 30 from DE cohorts and 7 from the SE. Median (range) age was 66 years; 19 (51%) were female. Fourteen were ISS stage I, 13 stage II, 8 stage III, 2 unknown. The median (range) number of prior lines of therapy was 6 (1-19). Thirty-two had prior bortezomib (20 refractory), 35 lenalidomide (18 refractory), and 26 had prior stem cell transplant. Fourteen patients had t(11;14), 4 had t(4;14), 5 had del 17p, and 17 had del 13q. Adverse events (AEs) in ≥20% of patients were nausea (49%), diarrhea (38%), vomiting (30%), anemia (27%), fatigue (24%). Grade 3/4 AEs (≥10%): thrombocytopenia (22%), anemia (19%), neutropenia (11 %). Serious AEs (≥2 patients): pyrexia (n=3), cough, malignant neoplasm progression, and sepsis (2 each); 2 (upper abdominal pain and anemia) were possibly related to venetoclax. Thirty (81%) patients have discontinued venetoclax: 24 due to PD, 3 for AEs (worsening shortness of breath, hypokalemia, and nausea), 2 withdrew consent, 1 due to death (brain hemorrhage following injury). Four deaths occurred (2 due to PD, 1 due to brain hemorrhage, 1 due to pneumopathy). Two of the 6 patients in the 600 mg cohort experienced DLTs of upper abdominal pain and nausea with abdominal pain. No patients met the criteria for laboratory or clinical TLS. Based on preliminary PK (n=21), the mean Cmax and AUC24 were ~dose-proportional at all studied doses (300, 600, 1200 mg) except 900 mg, and dose-normalized venetoclax exposure in MM was similar to that in CLL and NHL pts. Thirty-two of the 37 patients were evaluable for preliminary efficacy (Table). Two patients, both t(11;14), achieved a complete response (1 at 600 mg and 1 at 900 mg). Responses were first achieved at 1.8 and 1.1 months and were maintained for 9.7 and 9.0 months, respectively (900 mg pt remains in CR). Among the 16 patients receiving 1200 mg in the DE or SE cohort, 6 of whom had t(11;14), 5 achieved SD, 6 experienced PD, and 5 are not yet evaluable. Conclusions: Venetoclax monotherapy had a tolerable safety profile in heavily-pretreated relapsed/refractory MM, and no new safety signals were observed compared to other venetoclax studies. The study continues to enroll in the SE cohort at 1200 mg. Responses (including CR) and longer time on venetoclax were observed in t(11;14) patients. These early results suggest that venetoclax has single agent activity, most prominently in t(11;14) patients. Figure 1. Figure 1. Disclosures Kumar: Celgene: Research Funding; Millenium/Takeda: Research Funding; Onyx: Research Funding; AbbVie: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation,; Skyline, Noxxon: Honoraria. Off Label Use: Venetoclax is an investigational drug that is not yet approved in this indication.. Vij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy. Kaufman:Janssen: Consultancy; Spectrum: Consultancy; Merck: Research Funding; Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; Novartis: Research Funding; Onyx: Research Funding. Mikhael:Sanofi: Research Funding; AbbVie: Research Funding; Celgene: Research Funding; Onyx: Research Funding. Moreau:Takeda: Other: Adboard; Janssen: Other: Adboard; Celgene: Other: Adboard; Novartis: Other: Adboard; Amgen: Other: Adboard. Alzate:AbbVie: Employment, Equity Ownership. Morris:AbbVie: Employment, Equity Ownership. Ross:AbbVie: Employment, Equity Ownership. Dunbar:AbbVie: Employment, Equity Ownership. Zhu:AbbVie: Employment, Equity Ownership. Maciag:AbbVie: Employment, Equity Ownership. Agarwal:AbbVie: Employment, Equity Ownership. Leverson:AbbVie: Employment, Equity Ownership. Enschede:AbbVie: Employment, Equity Ownership. Humerickhouse:AbbVie: Employment, Equity Ownership. Touzeau:AbbVie: Research Funding.

Treatment Sequencing Patterns in Medicare-Enrolled Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2120-2120 ◽  
Author(s):  
Shuling Li ◽  
Tanya Natwick ◽  
Akeem Yusuf ◽  
Irena Sarah Vidito ◽  
Khalid Mezzi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Index Date ◽  
Employment Equity ◽  
Drug Regimens ◽  
Medicare Patients ◽  
Equity Ownership ◽  
Treatment Sequencing ◽  
Line Of Therapy ◽  
The Impact ◽  
Treatment Sequences

Abstract Introduction: Over the last decade, several novel therapies have been approved for multiple myeloma (MM) leading to significant improvement in the prognosis of MM patients. MM patients are often treated with multiple lines of therapy as relapse occurs. With the numerous options of therapeutic agents and novel combinations of regimens, the treatment for MM has become more complicated. However, little is known regarding the treatment sequencing patterns for Medicare patients with MM. In this study, we described the use of drug regimens by lines of therapy and characterized treatment sequences in Medicare patients with MM. Methods: Using a validated algorithm (Princic et al. Blood 2015;126:4521), we identified adult MM patients (≥ 18 years old) in 2008-2011 from the Centers for Medicare & Medicaid Services 100% Hematologic Cancer file (2007-2012) who began first-line (1L) treatment. Patients who advanced to second-line (2L), third-line (3L), and fourth-line (4L) were identified if a 90 day gap in all treatments was observed or when a drug was added to a regimen >90 days after the line index date. Drug regimens were based on National Comprehensive Cancer Network MM treatment guidelines and were identified using National Drug Code and Healthcare Common Procedure Coding System codes. Patients were included in the study if they received monotherapy, doublets, or triplets at 1L. The study period was from the 1L initiation date to the earliest of death, disenrollment from Medicare Parts A, B, and D coverage, receipt of treatments other than the above-mentioned drug regimens, or December, 31, 2012. We described the distribution of type of drug regimens by lines of therapy, overall and by age defined at MM index date, and characterized treatment sequencing patterns for patients who advanced to 2L, 3L, and 4L by type of drug regimens in the prior line of therapy, respectively. Results: In total, 12563 MM patients initiated 1L therapy. Of these, 9% were aged 18-64 years (enrolled in Medicare due to disabilities), 42% aged 65-74 years, and 49% aged ≥ 75 years. Most patients were white (78%) and more than half were female (53%). We identified 5647 (45%), 2243 (18%), and 773 (6%) patients who advanced to 2L, 3L, and 4L, respectively. Overall, doublets were the most common 1L regimen (62%), followed by monotherapy (21%) and triplets (17%). Most common treatments for monotherapy in 1L were dexamethasone (52%), lenalidomide (21%), and bortezomib (17%). The pattern was similar among patients who advanced to a 2L, 3L, or 4L, respectively, though more triplets were used at advanced lines. For 1L therapy, only 12% of patients aged ≥ 75 years received triplets, in contrast to >20% of triplet use in 3L and 4L respectively (Table). Of patients who received monotherapy in 1L and advanced to 2L, 37% continued monotherapy and 63% switched to more dense regimens (doublets, 53%; triplets 10%). Of patients who received doublets in 1L and advanced to 2L, 58% continued doublets, 22% switched to triplets, and 20% to monotherapy. Of patients who received triplets in 1L and advanced to 2L, 26% continued triplets and 74% switched to less dense regimens (doublets, 47%; monotherapy, 27%). Treatment sequencing patterns were similar for patients who advanced to 3L and 4L with monotherapy or doublets in prior lines, while the proportion of patients who repeated triplets increased to about 32% in 3L and 37% in 4L (Figure). Conclusions: Among Medicare patients with MM, doublets were the most frequently used regimens across all lines of therapy, while triplets were used in more advanced lines. Patients on monotherapy or doublets were more likely to retain their treatment pattern when they advance to the next line of therapy, while those on triplet regimen were more likely to switch to a less dense regimen when they advance to their next line of therapy. Fewer patients of older age (75+ years) were prescribed triplet therapies, however triplet use in this patient group increases in more advanced lines. These results provide a baseline description of treatment patterns from which we will be able to benchmark the impact of the recent introduction of novel agents and their use in elderly MM patients. Further studies assessing the comparative effectiveness and benefit-risk of treatment sequences are warranted. Figure Figure. Disclosures Yusuf: Amgen Inc.: Employment, Equity Ownership. Vidito:Amgen Inc.: Employment, Equity Ownership. Mezzi:Amgen Inc.: Employment, Equity Ownership. Werther:Amgen Inc.: Employment, Equity Ownership.

A New Multinational Observational Study In Multiple Myeloma: Initial Report Of The PREAMBLE Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1964-1964
Author(s):  
Ravi Vij ◽  
Mehdi M. Moezi ◽  
Robin Foà ◽  
Gordon Cook ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Research Funding ◽  
Clinical Effectiveness ◽  
Novel Therapies ◽  
Employment Equity ◽  
The Us ◽  
Equity Ownership ◽  
Baseline Characteristics

Abstract Introduction The advent of novel immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have improved clinical outcomes of multiple myeloma (MM) in the past decade. Clinical trial data have shown combination novel therapies (IMiD+PI) can provide even further improvement. The PREAMBLE (Prospective Research Assessment in Multiple Myeloma: an Observational Evaluation) is a global study designed to evaluate clinical effectiveness, healthcare resource utilization, and patient-reported outcomes associated with novel therapies for treatment of relapsed or refractory MM (R/R MM) in the real-world daily practices in the US and Europe. We describe the study design and baseline characteristics of the first 111 patients enrolled. Methods This is a prospective, observational, longitudinal cohort study of adult patients with R/R MM who received at least 1 prior therapy and initiated treatment with IMiDs, PIs, or IMiDs+PIs within 90 days prior to or 30 days after enrollment. Follow-up is up to 3 yrs after consent. Patients receive standard of care treatment as determined by the treating physician. Planned enrollment is 1000 patients in North America (NA) and Europe (EU; France, Germany, Italy, and UK). Results As of June 28, 2013, 111 patients from 63 sites in NA (n=64) and EU (n=47) have been enrolled. Baseline characteristics are summarized in Table 1. Cytogenetics (by FISH) was determined in 51% (n=57) of patients; of these, 16% (n=9) were high risk with del 17p (78%) as the predominant abnormality. Baseline treatment varied by region: of the patients in NA, IMiDs were used in 44% (n=28), PIs in 36% (n=23), and IMiD+PI in 20% (n=13) versus 60% (n=28), 34% (n=16), and 6% (n=3), respectively, in EU. Of the 16% high risk patients and the 25% of patients initially diagnosed at ISS stage III, none received IMiD+PI. The percentage of patients who received only 1 prior regimen at enrollment was 46% (n=26) in the IMiD group, 41% (n=16) in the PI group, and 63% (n=10) in the IMiD+PI group while the percentage of patients who received 3 or more prior regimens was 16% (n=9) in the IMiD group, 36% (n=14) in the PI group, and 6% (n=1) in the IMiD+PI group. Median time from diagnosis to enrollment for patients receiving IMiDs was 43 months, PIs was 42 months, and IMiDs+PIs was 33 months. Conclusion PREAMBLE provides a rich data source for evaluation of clinical, economic, and humanistic outcomes in patients treated for R/R MM. Initial data suggest different treatment patterns between patients in the US and in EU. Continued follow-up and larger sample size may help identify factors associated with different treatment choices and impact on clinical effectiveness, tolerability, resource utilization, and humanistic outcomes in patients treated for R/R MM. Disclosures: Vij: Celgene: Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Millennium: Speakers Bureau; BMS: Honoraria; Lilly: Honoraria. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Kaya:Millennium: Honoraria, Speakers Bureau. Durie:Millennium: Consultancy; Onyx: Consultancy; Celgene: Consultancy. Cella:BMS: Consultancy. Annemans:BMS: Consultancy. Su:BMS: Employment, Equity Ownership. Mukhopadhyay:BMS: Employment, Equity Ownership. Le:BMS: Employment. Petrucci:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria.

PFS2 In Elderly Patients With Newly Diagnosed Multiple Myeloma (NDMM): Results From The MM-015 Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 405-405 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Teresa Petrucci ◽  
Robin Foà ◽  
John V. Catalano ◽  
Martin Kropff ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Employment Equity ◽  
Advisory Committees ◽  
Long Term Treatment ◽  
Equity Ownership ◽  
Line Setting ◽  
The Impact

Abstract Introduction In a phase 3 trial of transplant non-eligible elderly (≥ 65 yrs) patients (pts) with NDMM, the combination of melphalan-prednisone-lenalidomide (LEN) followed by LEN maintenance (MPR-R) reduced the risk of progression by 60% compared with 9 cycles of MP (HR=0.40; P < 0.001) and by 51% compared with 9 cycles of MPR (HR=0.49; P < 0.001) (Palumbo, NEJM. 2012). The progression-free survival (PFS) benefit was seen in all patient types. With a median follow-up of 53 mos, the median overall survival (OS) was similar across the 3 treatment (Tx) groups (54 mos for MPR-R vs. 52 mos for MPR vs. 55 mos for MP) (Dimopoulos, ASH 2012; abstract 944). The similar OS benefit seen across the 3 arms could be due in part to the availability of more effective Tx options in subsequent lines of therapy. Assessment of PFS2, defined as the time from initial randomization to time of objective disease progression (PD) after next-line of therapy or death from any cause, has recently been proposed as a surrogate for OS, particularly for trials evaluating maintenance Tx (EMA guideline, www.ema.europa.eu). Therefore, data from MM-015 were analyzed to estimate PFS2 in pts treated with MPR-R, MPR, or MP. Methods The MM-015 study design has been previously described (Palumbo, NEJM. 2012). Refractory multiple myeloma pts who progressed during MM-015 study could receive LEN 25 mg (D1–21/28-day cycle) ± dexamethasone 40 mg (on days 1–4, 9–12, and 17–20) as part of an open-label extension phase, or any other anti-myeloma Tx outside of the protocol as part of the follow-up phase. The data of PD following 2nd-line Tx was not collected prospectively; therefore, the start of 3rd-line Tx was used as a surrogate for analyzing the PFS2 endpoint. The assessment included data up to July 31, 2012 (median follow-up: 53 mos after initial randomization). Results A total of 459 pts were randomized to MPR-R (n= 152), MPR (n= 153), or MP (n= 154). At the time of the data cut-off, fewer pts in the MPR-R group had started 2nd-line Tx (53%) compared with the MPR and MP groups (77% and 82%, respectively) due to the improved PFS seen with MPR-R in the 1st-line setting. Most pts in the MP group “crossed over” to receive LEN as 2nd-line Tx (72%); choice of 2nd-line Tx in the MPR-R group was heterogeneous (Table). Median PFS2 was significantly higher with MPR-R (39.7 mos) vs. MP (28.5 mos; HR=0.71; log-rank P = 0.013) (Figure). The safety profile of continuous therapy with LEN was predictable and manageable with little evidence of cumulative toxicity and low second primary malignancy risk (Delforge, IMW 2013: abstract O-17). Conclusion PFS2 was markedly improved in the MPR-R group vs. the MP group. LEN provided a durable progression-free interval also when including the impact of 2nd-line Tx, confirming the clinical benefits of continuous LEN Tx. The benefit of MPR-R was apparent regardless of subsequent Tx; long-term treatment with LEN did not affect the efficacy of subsequent therapy. Use of continuous LEN in the 1st-line setting in combination with MP is more beneficial than sequential use of MP and LEN. PFS and PFS2 were improved with MPR-R; OS was similar among the 3 Tx groups; the reason for this is unclear, but may be related to the impact of subsequent Tx (i.e., 3rd and 4th line), which was more frequently needed in the MPR and MP groups. Disclosures: Dimopoulos: Orthobiotech: Honoraria; Celgene Corporation: Honoraria. Off Label Use: Lenalidomide in the frontline and maintenance treatment of multiple myeloma. Petrucci:Celgene Corporation: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Catalano:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Yu:Celgene Corporation: Employment, Equity Ownership. Grote:Celgene Corporation: Employment, Equity Ownership. Jacques:Celgene Corporation: Employment, Equity Ownership. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria.

scholarly journals Incidence and Survival Impact of Self-Reported Symptom and Psychological Distress Among Patients with Multiple Myeloma

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 679-679
Author(s):  
Joshua R Richter ◽  
Noa Biran ◽  
Dhakshila Paramanathan ◽  
Srikesh Arunajadai ◽  
Victoria DeVincenzo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chronic Disease ◽  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Survival Rates ◽  
Employment Equity ◽  
Advisory Committees ◽  
Distress Score ◽  
Equity Ownership

Abstract Background: Advances in the management of multiple myeloma (MM) have significantly extended survival and dramatically reduced painful skeletal-related events for most patients. As MM is evolving to a chronic disease increased attention towards symptom and psychological impact is required. We sought to determine the incidence of self-reported pain, depression, financial and family burden, and impairment of performance status in a cohort of patients with MM receiving outpatient therapy at a tertiary cancer center and to determine the correlation of total distress with survival. Methods: The Living with Cancer (LWC) patient reported outcome (PRO) instrument is a statistically validated tool (ASCO Palliative Care Symposium 2016) that evaluates distress from the point of view of the advanced cancer patient. The 7-item 5-level Likert survey measures 4 personhood domains (performance status, pain, burden [financial and family], depression). The questions are also weighted by the patient with regards to importance, yielding a total score range 0-112. In a pilot study of advanced cancer patients a score of &gt;28 was associated with an increased likelihood of physicians' (blinded) opinion regarding need for end-of-life care discussions (J Palliative Med 2016). For individual survey items, a self-reported rating of 2-4 was considered to indicate patient concern. Results: 239 patients with MM completed the LWC PRO between Sept 2015 and Oct 2016. Patients were 57% male with a median age 67 years. 48% of patients were concerned that they could not do the things they wanted to do, with 33% reporting decreased performance status. Financial toxicity concerns were self-reported by 44%, with family burdens noted in 24%. Although depression was reported by only 15%, 41% reported lack of pleasure. Pain was self-reported as a concern by 36%. With a median follow up of 316 days since LWC completion, 13% of patients had died. A high total distress score (&gt;28) was noted in 57 (24%) and associated with a decreased survival rate compared to the 182 (76%) patients with a low total distress score (p&lt;0.05). The 6 month survival rates from the completion of the LWC survey for patients with high/low distress scores were 86% and 96% respectively, and 12 month survival rates were 76% and 87% respectively. Conclusions: Despite dramatic improvements in survival among patients with MM, symptom, financial, and psychosocial concerns continue to plague patients. As a chronic disease, additional attention to addressing these issues is required. Figure 1 Figure 1. Disclosures Richter: BMS: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Biran: Celgene, Amgen: Consultancy, Speakers Bureau; Takeda: Speakers Bureau. Paramanathan: COTA: Employment. Arunajadai: COTA: Employment. DeVincenzo: COTA: Employment. Pe Benito: COTA: Employment. Gruman: COTA: Employment. Kaur: COTA: Employment. Hervey: COTA: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Schultz: COTA: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Paddock: COTA: Employment, Equity Ownership. Pecora: Caladrius Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Siegel: Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. Goldberg: Ariad: Speakers Bureau; Pfizer: Honoraria; COTA: Employment, Equity Ownership; Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Celgene: Speakers Bureau.

scholarly journals US Cost Burden of Relapsed Refractory Multiple Myeloma during Third and Later Lines of Treatment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4725-4725
Author(s):  
Gene Felber ◽  
Chi-Chang Chen ◽  
Jenny Willson ◽  
Chris Bell ◽  
Edgar Simard ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Healthcare Costs ◽  
Research Funding ◽  
Similar Distribution ◽  
Cost Burden ◽  
Novel Therapies ◽  
Employment Equity ◽  
Mean Values ◽  
Equity Ownership ◽  
Incident Cohort

Background: Several novel therapies for multiple myeloma (MM) have been approved in recent years. While these therapies have demonstrated improvement in real-world tumor responses and progression-free survival, the cost burden of late-line relapsed refractory MM is not well understood. The objective of this retrospective cohort analysis of US claims data was to examine total, MM-related, and adverse event (AE)-related healthcare costs for patients with MM at different lines of treatment (LOTs), with a focus on patients at third (3L) or later (4L+) LOT. Methods: The study identified an incident cohort of treatment-naïve patients with MM aged ≥18 years from the PharMetrics Plus (IQVIA™, Durham, NC) database of US commercial claims and included patients had a first diagnosis of MM (Index date) between January 1, 2012 and December 31, 2016 and received ≥1 MM therapy during the ≥1-year follow-up period. Endpoints included all-cause and MM-related costs per patient per month (PPPM), common AEs, AE-related costs per episode, and proportion of patients requiring AE-related hospitalization. Descriptive analyses were conducted based on LOT (first-line [1L], second-line [2L], 3L and 4L+) which was defined using all MM drugs of interest observed within 28 days of use of the first MM drug, whereas end of a LOT was identified using a 90-day gap in the therapy regimen or use of a new agent outside the 28-day window. All-cause and MM-related costs were compared between patients indexed from 2012-2014 and 2015-2017 (ranges based on the availability of new MM drugs) using a univariate generalized model with log link and gamma distribution. Results: Of the 2,120 patients in the incident cohort, 799 (37.7%) and 390 (18.4%) patients received 3L and 4L+ treatments, respectively. Mean (standard deviation) age at initial MM diagnosis was 58.9 (8.9) and 58.8 (8.6) years for patients progressing to 3L and 4L+. Patients at 3L or 4L+ had greater use of novel therapies (29.2% and 66.9%, respectively) vs patients at 1L (1.4%) and 2L (12.0%). Mean all-cause and MM-related total costs PPPM were higher in 3L and 4L+ vs the mean costs for the entire cohort (Table 1). Costs were significantly greater in patients indexed later (2015-2017) vs earlier (2012-2014) during the study (before inflation adjustments). The most frequent AEs after initial MM diagnosis included hematologic AEs (anemia [79.3%], neutropenia [40.9%], and thrombocytopenia [38.2%]), pneumonia (32.6%), and bone pain (72.9%). The median duration of most AEs was short (1.0-5.0 days). The AE-related cost per episode of these AEs was high and increased during later lines of therapy, largely driven by increased inpatient and outpatient costs (Table 2). Costs were highest across lines of therapy for anemia, neutropenia and pneumonia. Conclusion: Patients in 3L and 4L+ of MM treatment incurred high healthcare costs that followed a typical cost distribution ranging from $18,000 to $22,000 PPPM (median values), with several patients incurring much higher costs that swung mean values substantially upward ($89,000 and $40,000 PPPM, respectively). Costs of managing AEs followed a similar distribution but were somewhat similar across LOTs, with median values ranging from $2,000 to $4,500 per episode and mean values exceeding $30,000 per episode. Additional research should focus on better understanding patients with high cost values, and other costs of managing MM and associated AEs that were not addressed in this analysis. Acknowledgments: Medical writing assistance was provided by Mary E. Morgan PhD at Fishawack Indicia Ltd UK and funded by GlaxoSmithKline. Programming was provided by Kainan Sun, an employee of IQVIA. This study (HO-18-18615) was funded by GlaxoSmithKline. Disclosures Felber: GlaxoSmithKline: Employment, Equity Ownership. Chen:IQVIA: Employment; GSK: Research Funding. Willson:GSK: Equity Ownership; GSK: Employment. Bell:GlaxoSmithKline: Equity Ownership; GlaxoSmithKline: Employment. Simard:GlaxoSmithKline (former employee): Employment; Medtronic (current employee): Employment. Nunna:GSK: Research Funding; IQVIA: Employment. Dharmani:GSK: Employment. Stirnadel-Farrant:GSK: Employment, Equity Ownership. Wang:GSK: Employment; BMS: Equity Ownership. Bruno:GSK: Employment; BMS: Equity Ownership.

scholarly journals Ex Vivo Activity of Immunotherapeutic Approaches Targeting CD38 Against Daratumumab-Resistant Multiple Myeloma Patient Samples

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1848-1848
Author(s):  
Maria Karvouni ◽  
Heyue Zhou ◽  
Arnika Kathleen Wagner ◽  
Qiangzhong Ma ◽  
Alamdar H. Baloch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Nk Cells ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Phase 1 ◽  
Employment Equity ◽  
Multiple Myeloma Patient ◽  
Myeloma Cells ◽  
Car T ◽  
Equity Ownership

Background: Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. The identification of CD38, a transmembrane glycoprotein overexpressed on MM cells, led to the development of target-specific therapeutics such as the FDA approved monoclonal antibody (mAb) Daratumumab (DARA). Although a valuable treatment option for refractory/relapsed (R/R) MM patients, DARA has a limited response rate of below 50%, which highlights the clinical need for novel therapeutics. Aims: Aiming to further exploit the therapeutic potential of CD38 in the MM setting, immunotherapies based on the novel anti-CD38 mAb CD38A2 were tested. Methods: For the first approach, the CD38A2 mAb -that binds to a unique, distinct from DARA's, CD38 epitope- was conjugated with either the alkylating agent Duomycin (ADC-136) or the microtubulin binder Duostatin (ADC-129). The ADCs were compared to DARA, in cultures of primary MM cells from patients refractory to DARA treatment. In a second approach, a chimeric antigen receptor (CAR) consisting of the CD38A2 scFv and the intracellular domains of CD28 and CD3ζ was used to transduce primary T and NK cells from R/R MM patients. The functionality of the CAR-T and CAR-NK cells was assessed in cytotoxicity assays against autologous myeloma cells. Results: ADC-136 demonstrated the most potent cytotoxicity against the MM cells with an IC50 of 6pM at day 6 following a single dose treatment. ADC-129 showed cell killing with an IC50 of 30pM, while DARA did not exhibit appreciable cytotoxicity. Regarding the cell therapy approach, patients' T and NK cells were effectively transduced, showing a CD38A2-CAR expression ranging between 11-68%. In functional assays, CAR-T and CAR-NK cells were assayed against autologous myeloma cells, where they exhibited an increase in target cell cytotoxicity, compared to the untransduced cells. Summary/Conclusion: Altogether, our preliminary findings demonstrate that CD38 targeting using CD38A2-based immunotherapies could be a viable therapeutic approach in R/R MM patients previously exposed to DARA. Currently, an anti-CD38 CAR-T therapy based on CD38A2 is being evaluated in Phase 1 studies in R/R MM patients by Sorrento Therapeutics, Inc. Disclosures Zhou: Sorrento Therapeutics Inc: Employment, Equity Ownership. Ma:Sorrento Therapeutics Inc: Employment, Equity Ownership. Zhu:Sorrento Therapeutics Inc: Employment, Equity Ownership. Zhang:Sorrento Therapeutics Inc: Employment, Equity Ownership. Kaufmann:Sorrento Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties.

scholarly journals Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1167-1167
Author(s):  
Andreas S. Buser ◽  
Laura Infanti ◽  
Andreas Holbro ◽  
Joerg Halter ◽  
Sabine Gerull ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Risk Scores ◽  
Employment Equity ◽  
Stem Cell Source ◽  
Equity Ownership ◽  
The Impact

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

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