Burden of Hospitalizations Due to Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disorder (EBV+PTLD) in Patients Who Failed First Line Rituximab or Rituximab Plus Chemotherapy Following Solid Organ Transplant (Post-SOT): A Retrospective Chart Review Study of German PTLD Registry

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and often aggressive disease in the setting of immunosuppression following solid organ transplant (post-SOT). About 50% of cases are associated with Epstein-Barr virus (EBV) infection of B cells, either due to reactivation of the virus after transplantation, or from primary EBV infection. Data remain very limited with respect to overall clinical and economic burden among EBV+PTLD patients (pts), particularly in the setting of pts who fail first line therapy. This retrospective chart review aimed to quantify the burden of hospitalization due to EBV+PTLD in post-SOT pts who failed first-line therapy in the real-world setting in Germany. Study Design and Methods: The German PTLD registry database was screened for pts with EBV+PTLD post-SOT who were refractory (failed to achieve complete [CR] or partial remission [PR]) to rituximab or rituximab plus chemotherapy (CT) or relapsed at any point after such therapy between 2000 to 2015. Pts with primary CNS PTLD were excluded. Pts without any outpatient visit or hospitalization record were excluded from the analysis (n of pts=1). Hospitalization data were reviewed by an experienced physician and adjudicated as PTLD relevant; details on diagnoses and procedures performed during hospitalization were collected from the first diagnosis of PTLD to the earliest of the following: death, loss to follow up or end of study period (Sep 1st, 2018). We estimated the mean number of hospitalizations, average length of inpatient stay per admission and the percentages of time spent in the hospital out of the total time following PTLD index date or treatment failure index date. The PTLD index date was defined as the first date of EBV+PTLD diagnosis; and the treatment failure index date was defined as the earliest date of pts who became refractory or relapsed to first-line therapy of rituximab or rituximab plus CT. Results: A total of 35 EBV+PTLD pts were analyzed. All had failed first line rituximab monotherapy. Median follow up time was 24.8 months from the PTLD index date. Median age at PTLD diagnosis was 47 years (range 18-75). Of these, 6 (17.1%) were polymorphic, 21 (60%) were diffuse large B cell lymphoma, 3 (8.6%) were Burkitt lymphoma, and 5 (14.3%) were other B-cell lymphoma. Among the 35 pts, 23 (65.7%) died: 12 from PTLD, 6 treatment-related, 1 from organ failure, and 4 from other causes. The vast majority of pts (29 out of 35) received CHOP-based CT following rituximab failure (2 other CT, 4 did not receive CT). All pts (100%) had at least one inpatient hospitalization after PTLD diagnosis and 16 (45.7%) pts had at least one ICU admission following PTLD index date. The mean number of PTLD hospitalizations following PTLD index date was 4 (SD 3.2, range 1-12) and the mean average length of stay per hospitalization was 23.8 days (SD 22.6, range 2-94). The mean proportion of time spent in the hospital out of total time at risk from PTLD index date was 20.5% (SD 27.6, range 0.1-100) with an average of 9.5% of time spent in the ICU setting during hospitalization stay (SD 22, range 0-99.5). The mean number of PTLD hospitalizations (n of pts=19) following first course CT failure index date was 2.1 (SD 1.9, range 0-7) and the mean average length of stay per hospitalization was 14.8 days (SD 8.6, range 6-31.6). The mean proportion of time spent in the hospital out of total time at risk from CT failure index date was 41.8% (SD 39.6, range 0-100) with an average of 26% time spent in the ICU setting (SD 39, range 0-100). Conclusions: This is the first study to quantify the hospitalization burden directly related to EBV+PTLD post-SOT in Germany. The results show that hospitalization burden in EBV+PTLD post-SOT pts failing first line rituximab monotherapy is substantial accounting for approximately 20% of patient's time after initial diagnosis of PTLD with around 10% spent in the ICU setting. This hospitalization burden is even higher and accounts for over 40% of time in pts after additional treatment failure to first CT with 26% spent in the ICU setting. Disclosures Zimmermann: Roche: Research Funding; Janssen: Other: Travel, accomodations expenses; Atara Biotherapeutics: Other: Travel, accomodations expenses, Research Funding; Celgene: Other: Travel, accomodations expenses. Xu:Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Zhang:Atara Biotherapeutics: Employment, Equity Ownership. Thirumalai:Atara Biotherapeutics: Employment. Watson:Atara Biotherapeutics: Employment, Equity Ownership. Trappe:Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress related travel support; Roche: Consultancy, Honoraria, Other: Congress related travel support, Research Funding; AbbVie: Consultancy, Other: Congress related travel support; Celgene: Other: Congress related travel support.

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Use of a New Rotary Powered Device for Bone Marrow Aspiration and Biopsy Yields Excellent Specimens Quickly and Efficiently.

Blood ◽

10.1182/blood.v114.22.4544.4544 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4544-4544

Author(s):

Ronan T. Swords ◽

Kevin R. Kelly ◽

Devalingam Mahalingam ◽

Stephen C. Cohen ◽

Larry J. Miller ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Clinical Evaluation ◽

Research Funding ◽

Bone Marrow Aspiration ◽

Swine Model ◽

Employment Equity ◽

Equity Ownership ◽

Specimen Quality ◽

The Mean

Abstract Abstract 4544 Background The importance of bone marrow aspiration and biopsy in the evaluation of hematopoietic and non-hematopoietic disorders is well established. Recently, a new FDA-cleared battery powered bone marrow biopsy system was developed to allow operators access to the bone marrow space quickly and efficiently. Aims The first aim of this study was to evaluate the quality of core specimens using the new powered device compared to specimens obtained using the traditional manual technique in a swine model. The second aim was to evaluate the safety and efficacy of the device in patients presenting for outpatient hematology clinic visits. Materials and Methods For the pre-clinical evaluation of the device, three anesthetized pigs were used for the study. The powered device (OnControl, Vidacare Corporation, San Antonio, TX, USA) was comprised of a battery powered driver and needle set. The manual device used was a T-Handle Jamshidi bone marrow biopsy needle (Cardinal Health, Dublin, OH, USA). Core biopsy samples obtained were assessed for length and sample quality and then submitted for analysis to a pathologist blinded to the device used. The clinical evaluation of the device was conducted in accordance with practice guidelines and directions for use. Data collection included insertion success, time from insertion to removal, specimen quality, operator satisfaction with control/function of the device and overall operator satisfaction based on a scoring system (0-5; 0=totally unacceptable, 5=outstanding). Results Twenty six samples were collected from the swine model (19 samples using the powered device and 9 using the manual technique). No cellular artifact or thermal damage was reported in any of the samples obtained. The mean lengths for samples obtained using the powered and manual techniques were respectively 19.4mm±1.6mm and 18.6mm±5.3mm. For the clinical evaluation of the device, 16 patients were recruited from 2 centers. Mean insertion time was 11.25±3.39 seconds and mean time from needle contact with skin to needle removal was 38.5±13.94 seconds. No complications were reported. Five operators rated the overall use of the device as outstanding in 75% of cases. Conclusions In this study, the manual and powered samples were equivalent in specimen quality. The powered device however, captured longer biopsies when compared to the manual technique. In the patients evaluated, the device was easy to use as well as being safe and effective. The mean procedural time was significantly faster than previously reported with a manual technique. A randomized study of the powered device compared to the manual technique is underway. Disclosures: Swords: Vidacare Corporation: Research Funding. Kelly:Vidacare Corporation: Research Funding. Mahalingam:Vidacare Corporation: Research Funding. Cohen:Vidacare Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Miller:Vidacare Corporation: Employment, Equity Ownership. Philbeck:Vidacare Corporation: Employment, Equity Ownership. Brenner:Vidacare Corporation: Consultancy, Research Funding. Giles:Vidacare Corporation: Research Funding.

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Effect of the Cytochrome P450 3A4 Inducers, Rifampicin and Dexamethasone, on the Pharmacokinetic, Pharmacodynamic and Safety Profile of Bortezomib In Patients with Multiple Myeloma (MM) and Non-Hodgkin's Lymphoma (NHL)

Blood ◽

10.1182/blood.v116.21.3983.3983 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3983-3983

Author(s):

Andrzej Hellmann ◽

Simon A. Rule ◽

Jan Walewski ◽

Ofer Shpilberg ◽

Huaibao Feng ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Proteasome Inhibition ◽

Employment Equity ◽

Advisory Committees ◽

Time Curve ◽

Once Daily ◽

Cyp3a4 Inducer ◽

Equity Ownership ◽

The Mean

Abstract Abstract 3983 Background: Bortezomib is primarily metabolized by cytochrome P450 (CYP) 3A4 and 2C19 enzymes. Effects of co-administration of rifampicin (a potent CYP3A4 inducer) and dexamethasone (weak CYP3A4 inducer) on the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles of bortezomib were evaluated. Methods: Patients with relapsed or refractory multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) were enrolled in this open-label, 2-stage, parallel-group study. In stage 1, patients were randomized (1:1) to receive 3 cycles of bortezomib (1.3 mg/m2) on d 1, 4, 8, and 11 q3wk either alone or in combination with rifampicin 600 mg once-daily on d 4 to 10 of cycle 3 only. Stage 2 patients received bortezomib at same dose and schedule in combination with dexamethasone 40 mg once-daily on d 1 to 4 and d 9 to 12 of cycle 3 only. Patients could continue with bortezomib monotherapy for up to 10 cycles in case of clinical benefit. For PK/PD, blood samples were collected before and through 72 hours following bortezomib administration on d 11 of cycles 2 and 3. PK was the primary endpoint, secondary endpoints included PD (proteasome inhibition) and safety. Results: 61 patients were enrolled (39 MM, 22 NHL) in the study. 13 were treated with bortezomib + rifampicin, 18 with bortezomib + dexamethasone, and 30 with bortezomib only. Co-administration of rifampicin reduced the mean bortezomib maximum plasma concentration (Cmax) by approximately 23% (118 vs 93 ng/mL) and the mean area under plasma concentration-time curve from 0 to 72 hours (AUC72) by approximately 45% (223 vs 123 ng.h/mL). Co-administration of dexamethasone had no effect on mean AUC72 (179 vs 170 ng.h/mL). The mean bortezomib Cmax was 20% lower after co-administration of dexamethasone (140 vs 119 ng/mL); however this difference in Cmax was within the observed variability in Cmax during cycle 2 (CV=38%) and cycle 3 (CV=45%). Mean (SD) maximum percent proteasome inhibition (Emax) and area under percent proteasome inhibition-time curve from 0 to 72 hours (AUE72h) were comparable for bortezomib alone and in combination with rifampicin (Emax: 61.9 [4.56] vs. 62.3 [3.81] and AUE72h: 836 [323] vs. 777 [358]). Co-administration of dexamethasone did not affect the Emax (66.7 [4.27] vs. 61.8 [6.69]) or AUE72h (1329 [638] vs. 1157 [381]). Safety profiles were consistent with prior bortezomib experience in this population. Drug-related serious adverse events and treatment discontinuations were reported in 7/30 (23%) and 8/30 (27%) in bortezomib-only, in 3/13 (23%) and 3/13 (23%) in bortezomib + rifampicin, and 3/18 (17%) and 5/18 (28%) in bortezomib + dexamethasone subgroups. Investigator-assessed responses (CR+PR) were observed in 13/17 MM and 6/13 NHL patients in bortezomib-only, in 6/9 MM and 3/4 NHL patients in bortezomib + rifampicin, and in 10/13 MM and 2/5 NHL patients in bortezomib + dexamethasone subgroups. Conclusions: Co-administration of dexamethasone did not affect the PK or PD profiles of bortezomib. Co-administration of rifampicin reduced bortezomib exposure (AUC) by approximately 45%. Patients receiving bortezomib concomitantly with strong CYP3A4 inducers, such as rifampicin, should be monitored for reduction in clinical effect, while concomitant administration of weak CYP3A4 inducers, such as dexamethasone, is not expected to affect the bortezomib pharmacologic profile. Disclosures: Off Label Use: Discussion of Velcade in NHL subtypes other than mantle cell lymphoma is included. Rule:Johnson & Johson: Consultancy, Speakers Bureau; Roche: Consultancy. Walewski:Johnson & Johnson: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Investigators fee. Shpilberg:Johnson & Johnson: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Feng:Johnson & Johnson: Employment. van de Velde:Johnson & Johnson: Employment, Equity Ownership. Patel:Johnson & Johnson: Employment, Equity Ownership. Skee:Johnson & Johnson: Employment. Girgis:Johnson & Johnson: Employment. Louw:Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Key Oncologics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Clinical and Economic Outcomes Associated with Emergency Department Visits in Patients with Immune Thrombocytopenia,

Blood ◽

10.1182/blood.v118.21.4209.4209 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4209-4209

Author(s):

Z John Lu ◽

Mark D. Danese ◽

Marc Halperin ◽

Melissa Eisen ◽

Robert Deuson

Keyword(s):

Emergency Department ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Primary Diagnosis ◽

Secondary Diagnosis ◽

Employment Equity ◽

Ed Visits ◽

Equity Ownership ◽

The Mean ◽

Total Charges

Abstract Abstract 4209 Introduction: Immune thrombocytopenia (ITP) is characterized by low platelet counts, spontaneous bruising, mucosal bleeding, and, more seriously, intracranial hemorrhage. The disease is associated with a high risk of complications, often requiring visits to emergency departments (ED), with possible subsequent hospitalization. To date, information about ED visits in ITP patients, including frequency, cost, hospitalization risk, and mortality risk, has not been well documented, although such data are critical to the understanding of the clinical and financial implications of poorly-controlled, chronic ITP. We used the 2007 Nationwide Emergency Department Sample (NEDS) to examine resource utilization, ED visits, and hospitalization charges in the US. Methods: The 2007 NEDS contains about 27 million ED records from over 970 hospitals in 27 Healthcare Cost and Utilization Project (HCUP) Partner States, representing a 20% stratified sample of US hospital-based ED visits. The database includes hospital and patient characteristics, diagnoses and procedures, disposition from ED including hospitalization and mortality, discharge diagnosis-related group (DRG) for subsequent hospitalizations, and total charges. Its large sample size enables analyses of relatively rare conditions such as ITP. All ED visits in the database were separated into two groups: visits with ITP as one of the diagnoses (ICD-9-CM diagnosis code of 287.31), and those without a diagnosis of ITP. Outcomes and resource use were separately evaluated in these two groups, as well as in several subgroups within the ITP group defined by age and whether the ITP diagnosis was the primary or a secondary diagnosis. Results: Approximately 8,348 (∼0.03%) of all ED visits in the 2007 NEDS database were in patients with ITP (28% as the primary diagnosis), of which nearly 60% were by female patients and 88% by adult patients (≥18 years old). Medicare or Medicaid was listed as the primary payer in 58% of the visits. Seventy-five percent of the ED visits in ITP patients led to hospitalizations, compared with less than 16% of ED visits in non-ITP patients (p < 0.0001). In ITP patients, 3% of the ED visits ended in death, compared with 0.6% in non-ITP patients (p < 0.0001). The mean total charges for ED visits in ITP patients were $1,650 compared with $1,495 for all others (p<0.0001). The average length of stay (LOS) during hospitalizations subsequent to ED visits was >1.5 days longer (6.5 vs. 5.0 days; p < 0.0001) for ITP patients. The mean total combined charges during the ED visit and resulting hospitalization were >60% higher ($47,000 vs. $29,000; p < 0.0001) for ITP patients. Subgroup analyses of ED visits in ITP patients by age showed that in the majority of visits by pediatric patients (<18 years old), ITP was identified as the primary diagnosis (61%) compared with only 24% among visits by adult patients. Furthermore, visits by adult ITP patients were less likely to result in routine discharge (18% vs. 50%), more likely to result in hospitalization (80% vs. 43%), and were associated with higher mortality compared with pediatric ITP patients (4% vs. 0.1%; p < 0.0001 for all comparisons). ED visits identified with ITP as the primary diagnosis were associated with a higher rate of subsequent hospitalizations (81% vs. 73%), but lower total charges and mortality ($1,490 vs. $1,710, and 2% vs. 4%) respectively, compared with those identified with ITP as a secondary diagnosis (p < 0.0001 for all comparisons). Conclusion: ED visits in ITP patients were associated with significantly worse outcomes, higher resource utilization, and greater total charges. For patients with ITP, younger age and a primary diagnosis of ITP were generally associated with better outcomes following ED visits. More robust and rigorous analyses controlling for patient and hospital heterogeneities will be conducted to confirm these findings. Disclosures: Lu: Amgen: Consultancy, Equity Ownership, Research Funding. Danese:Amgen: Consultancy, Research Funding. Halperin:Amgen: Consultancy, Research Funding. Eisen:Amgen: Employment, Equity Ownership. Deuson:Amgen: Employment, Equity Ownership.

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First-Line Treatment and Management of Chronic Myeloid Leukemia (CML) in Clinical Practice: Update of > 1800 Patients (Pts) in the WORLD CML Registry

Blood ◽

10.1182/blood.v120.21.3750.3750 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3750-3750

Author(s):

Jorge E. Cortes ◽

Ricardo Pasquini ◽

Hagop M. Kantarjian ◽

David Joske ◽

Luis A Meillon ◽

...

Keyword(s):

Clinical Practice ◽

Board Of Directors ◽

Research Funding ◽

Disease Status ◽

First Line ◽

Employment Equity ◽

Advisory Committees ◽

Time Points ◽

The World ◽

Equity Ownership

Abstract Abstract 3750 Background: The WORLD CML Registry is a multinational, prospective registry established to longitudinally assess global patterns of current and evolving methods for diagnosis, treatment, and clinical outcome measures in pts with CML and to compare clinical practice patterns to management recommendations provided by the European LeukemiaNet (ELN; Baccarani M, et al. J Clin Oncol. 2009;27:6041–6051). Here, we report overall efficacy and safety data from this registry, as well as clinical monitoring practices and outcomes in the subgroup of pts with CML in chronic phase (CP) treated with first-line imatinib. Methods: Pts (≥ 16 y of age) with CML in CP, accelerated phase (AP), or blast crisis (BC) within 6 mo + 2 weeks of confirmed CML diagnosis were enrolled at sites in Latin America, Asia-Pacific, the United States, Russia, Turkey, the Middle East, and Africa. Baseline demographics and medical history were collected at enrollment; disease status and management information were collected at approximate 6-mo intervals or when there was a change in disease status/management. Adverse events (AEs) were collected only if they resulted in a dose/regimen change, nonadherence to treatment, or death. Results: A total of 1837 of the 1889 pts enrolled between February 2008 and December 31, 2010, were evaluable (ie, had confirmed informed consent forms and no protocol deviations) and are the basis for this analysis. Median age was 47 y (range, 16–92 y), and 58% of pts were male. CML diagnosis was established using hematologic (91% of pts), bone marrow (82%), cytogenetic (83%), and molecular (polymerase chain reaction [PCR]; 53%) assessments. Nearly all pts (94%) were initially diagnosed in CP (Table). As of the data cutoff (December 31, 2010), median overall survival (OS) and median event-free survival (EFS) in all pts were not reached. Estimated OS and EFS rates at 3 y were 90.4% and 74.8%, respectively. AEs reported in ≥ 1% of pts were thrombocytopenia (3%) and neutropenia (2%). In the CML-CP subgroup, imatinib (Glivec®/Gleevec®) was administered as first-line therapy (in clinical practice or in a clinical trial) to 63% of pts (n = 1083). Disease burden in CML-CP pts on imatinib over time was most commonly assessed via blood counts (Table). Cytogenetic and molecular assessments were used in a minority of CML-CP pts at most time points. Only 50% of pts had a disease assessment at 3 mo (hematologic, 49%; cytogenetic, 10%; molecular, 15%). Of the pts on first-line imatinib outside of a clinical trial setting (n = 1024), 95 (9%) had their dose increased, 77 (8%) had their dose decreased, and 82 (8%) were switched to nilotinib or dasatinib. In all CML-CP pts treated with first-line imatinib, estimated OS and EFS rates at 3 y were 92.1% and 76.6%, respectively (Table). Estimated OS and EFS rates at 3 y were higher in pts who had higher imatinib exposure (treatment received ≥ 85% of total days) vs pts who received imatinib treatment on < 85% of days. Conclusions: The majority of CML-CP pts treated with first-line imatinib did not have cytogenetic or molecular assessments in accordance with current ELN recommendations, particularly at early time points. Additionally, pts who had higher drug exposure to imatinib had higher estimated OS and EFS rates at 3 y than those who did not. Disclosures: Cortes: Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding. Kantarjian:Novartis Pharmaceuticals Corp: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding. Piccolo:Novartis Pharma AG: Employment. Zernovak:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Sivarathinasami:Novartis Healthcare Pvt. Ltd,: Employment. Eng:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Kim:Novartis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ARIAD: Research Funding; II-Yang: Consultancy, Honoraria, Research Funding. Hughes:Novartis Pharmaceuticals Corp: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Ariad: Consultancy; CSL: Research Funding.

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Lenalidomide Treatment For Lower Risk Non-Deletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Prior To Azanucleosides

Blood ◽

10.1182/blood.v122.21.1507.1507 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1507-1507

Author(s):

Rami S Komrokji ◽

Maria G. Corrales-Yepez ◽

Najla H Al Ali ◽

Eric Padron ◽

Jeffrey E Lancet ◽

...

Keyword(s):

Overall Survival ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Research Funding ◽

Response Rates ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

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An Evaluation of Molecular Response in a Phase 2 Open-Label, Multicenter Confirmatory Study in Patients (pts) with Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (r/r ALL) Receiving Treatment with the BiTE® Antibody Construct Blinatumomab

Blood ◽

10.1182/blood.v124.21.3704.3704 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3704-3704 ◽

Cited By ~ 5

Author(s):

Nicola Goekbuget ◽

Hagop Kantarjian ◽

Monika Brüggemann ◽

Anthony Stein ◽

Ralf C. Bargou ◽

...

Keyword(s):

Research Funding ◽

Pcr Amplification ◽

Relapse Free Survival ◽

First Line ◽

Employment Equity ◽

Advisory Committees ◽

Free Survival ◽

Minimum Sensitivity ◽

Equity Ownership ◽

Grade 3

Abstract Background: Blinatumomab is an investigational bispecific T-cell engager (BiTE®) antibody construct designed to direct cytotoxic T cells to CD19-expressing B cells. In a study in minimal residual disease (MRD)-positive ALL, 80% of pts achieved MRD-negative status after receiving one treatment cycle of blinatumomab (Topp MS, et al. J Clin Oncol. 2011;29:2493-8). For pts with newly diagnosed ALL, persistence of MRD after first-line treatment predicts disease recurrence. However, only limited data are available about the relationship between MRD and outcome in adult pts with r/r ALL. Therefore, the aim of this secondary analysis was to evaluate MRD responses and their relationships to other efficacy indices in adult pts with r/r ALL receiving blinatumomab in this phase 2 study. Methods: Eligibility criteria included adult pts ≥18 years, with Philadelphia chromosome negative B-cell r/r ALL who were primary refractory or refractory to first salvage, had their first relapse within 12 months of first remission or allogeneic hematologic stem cell transplantation (HSCT), or received second or later salvage. Blinatumomab was dosed via continuous IV infusion at 28 μg/d (cycle 1 only: 9 μg/d on days 1-7, 28 μg/d on days 8-28) for up to five cycles (one cycle: 4 weeks on, 2 weeks off). The primary endpoint was complete remission (CR: ≤5% blasts with platelets >100,000/µL, absolute neutrophil count >1000/µL) or CR with partial hematologic recovery (CRh*: platelets >50,000/µL, absolute neutrophil count >500/µL) within the first two treatment cycles. MRD in bone marrow was assessed at a central laboratory using allele-specific real-time quantitative PCR. Two MRD-based exploratory endpoints were analyzed: MRD response (no PCR amplification at a minimum sensitivity of 10-4 or <10-4 leukemic cells by PCR) and complete MRD response (no PCR amplification at a minimum sensitivity of 10-4) within the first two treatment cycles. Results: Of 189 treated pts (median [range] age = 39 [18–79] years), 81 (43%) pts had a CR (n = 63, 33%) or a CRh* (n = 18, 10%) during the first two treatment cycles. In the subgroup of pts with a CR/CRh* and evaluable MRD data (n = 73), 60 (82%) pts had an MRD response. Of those, 51 (70%) pts had a complete MRD response. The majority of those who achieved a CR/CRh* also achieved a complete MRD response regardless of the number of prior lines of salvage therapy (Table 1). Of all treated pts, 64 (34%) pts had prior HSCT. In pts who achieved CR/CRh*, the rate of MRD response was 81% in pts without and 85% in pts with prior HSCT. In pts who achieved CR/CRh*, the median (95% CI) duration of overall survival was 11.4 (8.5, not estimable) months for those with a MRD response and 6.7 (2.0, not estimable) months for those with no MRD response. The median (95% CI) duration of relapse-free survival was 6.9 (5.5, 10.1) months in patients with a MRD response and 2.3 (1.2, not estimable) months in patients with no MRD response. The HSCT realization rate did not differ significantly between pts with CR/CRh* and a MRD response and those with CR/CRh* and no MRD response (31% and 43%, respectively). Seventeen pts classified as nonresponders per protocol had ≤5% blasts and no evidence of disease, but recovery of peripheral counts did not meet criteria for CRh*. Ten of these 17 pts had evaluable MRD assessments; 50% (5/10) had MRD response and 20% (2/10) had complete MRD response. The clinical significance of this finding remains open. Grade ≥3 adverse events regardless of causality and occurring in >10% of all treated pts during treatment until 30 days after treatment were febrile neutropenia (25%), neutropenia (16%), and anemia (14%). Grade 3 cytokine release syndrome (CRS) was reported in three (1.6%) patients. Three (1.6%) patients had grade 4 neurologic events, all resolved. Twenty-one (11%) patients had grade 3 neurologic events, 17 were resolved, with 4 events unresolved at death or unknown. Conclusion: In this largest study to date of adult pts with r/r ALL with PCR-based central assessment of MRD, pts who achieved CR/CRh* during single-agent treatment with blinatumomab had high MRD response rates. The exploratory analyses suggested that within pts with a CR/CRh*, those who did not achieve MRD responses tended to have shorter durations of overall and relapse-free survival. These results are consistent with prior reports highlighting the importance of achieving an MRD response in first-line therapy. Disclosures Goekbuget: Amgen Inc.: Consultancy, Honoraria, Research Funding. Off Label Use: This presentation will discuss the off-label use of blinatumomab, as this agent is not approved for use by the FDA, EMA or any other regulatory authorities. Kantarjian:Amgen Inc.: Research Funding. Brüggemann:Amgen Inc.: Consultancy, Research Funding. Stein:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees. Bargou:Amgen Inc.: Consultancy, Honoraria. Dombret:Amgen Inc.: Research Funding. Heffner:Amgen Inc.: Honoraria, Research Funding; Biotest: Research Funding; Dana Farber CI: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Idera: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Pharmacyclics: Honoraria, Research Funding; Onyx: Research Funding; Spectrum: Research Funding; Talon Therapeutics: Research Funding. Rigal-Huguet:Amgen, Inc.: Consultancy; Ariad: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Litzow:Amgen Inc.: Honoraria, Research Funding. Zugmaier:Amgen Reseach (Munich) GmbH: Employment; Amgen Inc.: Equity Ownership. Jia:Amgen Inc.: Employment, Equity Ownership. Maniar:Amgen Inc.: Employment, Equity Ownership. Huber:Amgen Research (Munich) GmbH: Employment; Amgen Inc.: Equity Ownership. Nagorsen:Amgen Inc.: Employment, Equity Ownership, Related to blinatumomab Patents & Royalties. Topp:Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Results from Phase 2 Trial Ongoing Expansion Stage of SL-401 in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Blood ◽

10.1182/blood.v128.22.342.342 ◽

2016 ◽

Vol 128 (22) ◽

pp. 342-342 ◽

Cited By ~ 8

Author(s):

Naveen Pemmaraju ◽

Andrew A. Lane ◽

Kendra L. Sweet ◽

Anthony S. Stein ◽

Sumithira Vasu ◽

...

Keyword(s):

Research Funding ◽

Plasmacytoid Dendritic Cell ◽

Phase 2 ◽

First Line ◽

Employment Equity ◽

Phase 2 Trial ◽

Major Response ◽

Expansion Stage ◽

Equity Ownership ◽

Stage 1

Abstract Background: SL-401 is a targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) and other hematologic malignancies. BPDCN is an aggressive hematologic malignancy of unmet medical need that often presents in bone marrow and skin, and may also involve lymph nodes and viscera. Long-term outcomes after treatment with chemotherapy have been very poor, with median overall survival from diagnosis of ~12 months, highlighting the need for novel therapies. Results from the Phase 2 trial of SL-401 in patients with BPDCN are reported here. Methods:This multicenter, single-arm Phase 2 trial of patients with BPDCN includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients with BPDCN or relapsed or refractory (r/r) AML received SL-401 as a daily IV infusion at 7, 9, 12, or 16 ug/kg/day for days 1-5 of a 21 day cycle. In stage 2, patients with BPDCN receive SL-401 at the dose determined in stage 1. Results: As of 7/25/16, 29 patients with BPDCN have received SL-401, including 16 first-line and 10 relapsed/refractory (r/r) adults and 3 pediatric patients (under compassionate use). The 26 adult patients (9+17 in stages 1&2) received SL-401 at 7 ug/kg (n=3 [stage 1]) or 12 ug/kg (n=23 [6+17 in stages 1&2]). The median adult age was 69 years (range: 29-82 years). In stage 1, 12 ug/kg was the highest tested dose for BPDCN; MTD was not reached in BPDCN. Results in AML (r/r) patients will be reported separately. The most common treatment-related AEs, all grades, were transient transaminase elevation (54%) and hypoalbuminemia (38%). Transient thrombocytopenia was also noted (19%). The most common ≥ Grade 3 treatment-related AEs were transient transaminase elevation (42%) and thrombocytopenia (19%). Two stage 1 patients developed capillary leak syndrome (CLS): gr 5 (7 ug/kg) and gr 4 (12 ug/kg). Safety precautions, including monitoring of albumin levels and body weight, were successfully implemented to minimize risk of severe CLS, which has not occurred in patients with BPDCN since adoption. Twenty-one of 26 adult patients were evaluable for response (response assessment from 3 recently treated patients are pending; 1 patient was discontinued for as yet unspecified reasons; and 1 patient treated at 7 ug/kg was not evaluable for response due to AE); median follow-up for evaluable patients was 6.9 months (range: 0.6-17.6 months). An 86% (18/21) ORR was observed in evaluable adult BPDCN patients. ORR in evaluable patients was 100% (14/14) in first-line and 57% (4/7) in r/r BPDCN. Of these, 92% (11/12) of first-line patients treated at 12 ug/kg had a CR (n=8) or clinical CR (CRc: a CR in non-skin organs with gross reduction in cutaneous lesions and residual microscopic skin disease) (n=3). 75% (9/12) of these patients remain progression free for 3+ to 16+ months (ongoing), including 4 patients who remain on SL-401 in remission (for 3+ to 12+ months [up to 16+ cycles], ongoing) and 5 additional patients who experienced a major response on SL-401 (3 CR, 1 CRc, 1 PR) and were then successfully bridged to stem cell transplant (SCT; 3 auto-SCT and 2 allo-SCT) and all remain progression free for 3+ to 16+months (ongoing) since first SL-401 dose. Notably, a patient with r/r BPDCN was recently bridged to allo-SCT following CRc on SL-401. Conclusions: SL-401 demonstrates robust single agent activity in BPDCN, including 86% ORR in all-lines, with multiple CRs, in evaluable patients. Six patients, including 1 r/r patient, have proceeded to SCT after achieving a major response from SL-401, and an additional 7 patients remain on SL-401 for up to 12+ months, ongoing. The SL-401 side effect profile remains manageable, and no unexpected AEs have emerged with increased treatment duration, drug exposure, and patient enrollment. Response duration, progression-free and overall survival data continue to be encouraging and updated data will be presented. Clinical trial information: NCT02113982. Disclosures Lane: N-of-1: Consultancy; Stemline Therapeutics: Research Funding. Sweet:Ariad: Consultancy, Speakers Bureau; Incyte Corporation: Research Funding; Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Novartis: Consultancy, Speakers Bureau. Stein:Seattle Genetics: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Stemline Therapeutics: Consultancy, Research Funding; Argios: Research Funding; Celgene: Research Funding. Wang:Immunogen: Research Funding; Incyte: Speakers Bureau. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. McDonald:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Lancet:Quantum First: Consultancy; Pfizer: Research Funding; Seattle Genetics: Consultancy; Novartis: Consultancy; Biopath Holdings: Consultancy; ERYtech: Consultancy; Karyopharm: Consultancy; Baxalta: Consultancy; Kalo Bios: Consultancy; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Boehringer-Ingelheim: Consultancy; Amgen: Consultancy. Kantarjian:Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; ARIAD: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding.

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Treatment Patterns and Outcomes Among Patients with Higher-Risk Myelodysplastic Syndromes Treated in a Real-World Setting: Electronic Medical Record-Based Data

Blood ◽

10.1182/blood.v128.22.5540.5540 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5540-5540

Author(s):

Jill A Bell ◽

Aaron Galaznik ◽

Eileen Farrelly ◽

Marlo Blazer ◽

Brian Seal ◽

...

Keyword(s):

Pharmaceutical Company ◽

Research Funding ◽

Employment Equity ◽

Line Therapy ◽

Company Limited ◽

Induction Type ◽

Wholly Owned Subsidiary ◽

Equity Ownership ◽

Diagnosis Date

Abstract Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders resulting in ineffective hematopoiesis primarily affecting older adults; median age of diagnosis is >70 years. Treatment decisions in MDS are largely based on a prognostic scoring system that has been incorporated into some drug labeling (NCCN 2016). The use of hypomethylating agents (HMAs) in patients with higher-risk (HR) MDS is supported by consensus guidelines, thus the purpose of this study was to examine factors influencing prescribing patterns in this subset of patients. Methods: This was a retrospective cohort study using a large United States electronic medical record database. Newly diagnosed HR MDS patients initiating first-line therapy (1LT) between 1/2008 and 7/2015 were followed for 1 year prior to and ≥ 60 days after diagnosis. Included patients were ≥18 years old with evidence of HR MDS identified as follows: 1) ≥1 inpatient claim with an HR MDS diagnosis code (ICD-9 code: 238.73; ICD-10 codes: D46.20, D46.21, D46.22), or 2) ≥2 outpatient claims with an MDS diagnosis code, with the first one coded for HR MDS ≥60 days but <1 year apart during the identification period. The date of the first HR MDS claim served as the index diagnosis date. 1LT was defined as an MDS-specific systemic agent initiated on or after the index diagnosis date and included all agents received within 30 days following the first infusion or fill date. Subsequent lines of therapy (LOT) were defined as an addition of a new MDS-specific agent >30 days after the initial chemotherapy agent(s) or a switch to another drug combination. Stem cell transplantation (SCT) was considered part of the LOT in which it occurred. All patients were followed until death or progression to acute myeloid leukemia (AML), loss to follow-up, or the end of study period (9/30/2015). Results: 345 patients newly diagnosed with HR MDS met the study criteria; 218 (63%) were treated with supportive care (including transfusions, hydroxyurea, colony-stimulating factors [CSFs], azole antifungals, erythropoiesis-stimulating agents [ESAs], or pain medications) or observation only and 127 (37%) were treated with MDS-directed therapy (HMAs, immunosuppressive therapy, induction-type therapy, SCT, or lenalidomide) ± supportive care (Table 1). Compared to untreated patients, a greater proportion of treated patients were male, had severe cytopenias (specifically, neutrophils <0.8 K/L and/or platelets <50 K/L), and had received a transfusion of either red blood cells or platelets during the baseline period (Table 1). In the treated population, most patients received only 1LT (n=111, 87%); 16 patients (13%) went on to second-line therapy, and 3 (2.3%) to third-line therapy. HMAs were the most utilized agents in 1LT, with 84 (66%) and 29 (23%) patients receiving azacitidine and decitabine, respectively. Lenalidomide was used in 6.3% of patients (n=8), and induction-type chemotherapy in 3.2% (n=4); no patients received immunosuppressive therapy only (cyclosporine or anti-thymocyte globulin). At median follow-up of 9 months (interquartile range [IQR]: 4, 16) for the treated population, 46 (36%) had died and 36 (28%) had progressed to AML. Within the population that received an HMA (n=113), age ≥75 years was approximately 50% for each agent; however, a greater proportion of patients who received azacitidine had a known marrow blast count of >5%, hemoglobin <10 gm/dL, and platelets <50 K/L at baseline (Table 2). At end of follow-up, 27% (n=23) and 36% (n=30) of azacitidine-treated patients had progressed to AML or died whereas 28% (n=8) and 41% (n=12) of decitabine-treated patients progressed to AML or died, respectively. Conclusions: Despite the existence of treatment guidelines for HR MDS patients and given the limitations of a retrospective study, the majority of patients in a real-world setting are not treated with MDS-specific agents. Younger age (<75 years) and more severe cytopenias may be factors considered in the decision of whether or not to treat HR MDS. If treated, HMAs are the most utilized therapy in these patients, with azacitidine predominating. Cytopenias at baseline may also influence the choice between azacitidine and decitabine, although survival and progression to AML appear similar between groups. References: National Comprehensive Cancer Network (NCCN) Guidelines in Oncology for MDS v.1.2016. Disclosures Bell: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Galaznik:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Farrelly:Takeda: Research Funding. Blazer:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Shih:Takeda: Research Funding. Ogbonnaya:Takeda: Research Funding. Dezube:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

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Outcomes of Plasma Cell Leukemia Patients in the Era of Next-Generation Novel Agents: A Single-Center Retrospective Cohort Study

Blood ◽

10.1182/blood-2020-141525 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-7

Author(s):

Alex Ge ◽

Chiung-Yu Huang ◽

Thomas Martin ◽

Jeffrey L. Wolf ◽

Nina Shah ◽

...

Keyword(s):

Plasma Cell ◽

Research Funding ◽

Progression Free Survival ◽

Novel Agents ◽

Next Generation ◽

First Line ◽

Advisory Committees ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy

Introduction Primary plasma cell leukemia (pPCL) is a rare and aggressive disease comprising 1-5% of all plasma cell dyscrasias. Although historically pPCL has been defined by circulating plasma cells (CPCs) ≥ 20% and 2.0 × 109/L, many series require only one of these two criteria for diagnosis. Over time there has been a pressing need to change the definition further in order to capture patients at an earlier stage of the disease. Recent studies have shown that multiple myeloma (MM) patients who have CPCs ≥ 5% but < 20% at diagnosis have similarly poor outcomes. These thresholds for defining pPCL have not been studied in the current era of novel agents. While bortezomib-based regimens have been shown to extend pPCL patient survival, studies with next-generation agents such as carfilzomib (CFZ), pomalidomide, and daratumumab (DARA) are still scarce. Methods We performed a single-center, retrospective study of patients who at diagnosis had pPCL (defined as CPCs ≥ 20% or 2.0 × 109/L) or had MM with < 20% CPCs (MM-CPC). Patients were treated at our institution between 1/1/2000-7/17/2020. Overall response rates were determined according to International Myeloma Working Group criteria. Overall survival (OS) was defined as the length of time between initiation of first line therapy and death. Progression-free survival (PFS) was defined as the length of time between initiation of first line therapy and first progression. OS and PFS were compared using log-rank tests. Results Of the 54 patients identified, 38 had pPCL and 16 had MM-CPC. The median age at diagnosis of the pPCL and MM-CPC groups were 59.2 (range 43-94) and 59.8 years (range 29-79), respectively, with a similar percentage of females, 47.4% vs. 37.5%. Both groups were similarly distributed by year of diagnosis; 76.3% and 62.5% of pPCL and MM-CPC patients were diagnosed between 2012-2020, respectively. The pPCL cohort had median CPCs of 40% (15-98) while the MM-CPC cohort had median CPCs of 4% (1-15). Median CPCs at diagnosis was 3.36 (0.44-179) × 109/L in the pPCL group compared to 0.33 (0.04-1.79) × 109/L in the MM-CPC group. Most patients for both groups were ISS stage III at diagnosis (57.9% in pPCL cohort, 56.2% in MM-CPC cohort). R-ISS assessment was not feasible due to missing data. A greater proportion of patients in the pPCL group (44.7%) had complex cytogenetics at diagnosis compared to the MM-CPC group (25.0%). All patients were exposed to at least one novel agent over the entire disease course. Of these patients, 50 (92.6%) were exposed to bortezomib, 45 (83.3%) to lenalidomide, 33 (61.1%) to CFZ, 22 (40.7%) to DARA, 13 (24.1%) to pomalidomide, and 4 (7.4%) to venetoclax. Twenty-four patients (44.4%) received an autologous stem cell transplant (ASCT). At the best response to treatment, 76.7%, 62.8% and 37.9% of patients achieved a partial response or greater to first, second and third line therapy, respectively. The median OS of the pPCL and MM-CPC groups was 34.5 and 35.5 months (p = 0.97) (Figure 1A), while the median PFS was 13.9 and 10.9 months (p = 0.52) (Figure 1B), respectively. The median follow-up was 28.1 months. No differences were observed for patients with CPCs < 20% compared to patients with CPCs ≥ 20% (p = 0.98). There was trend towards a better survival for patients with CPCs < 2 × 109/L compared to CPCs ≥ 2 × 109/L (p = 0.35). Since we did not observe any meaningful difference in OS or PFS between the pPCL and MM-CPC groups, we combined these groups for further survival analysis. Patients exposed to either DARA or CFZ (n = 37) had a median OS of 59.2 months, while patients exposed to neither drug (n = 17) had a median OS of 11.7 months (p = 0.02) (Figure 1C). ASCT was associated with a prolonged median OS (66.8 months vs. 17.2 months, p = 0.0001) (Figure 1D), while a complex karyotype at diagnosis was associated with a poorer median OS (17.4 months vs. 66.8 months, p = 0.01). Conclusions In the era of next-generation novel agents, overall and progression-free survival of pPCL and MM-CPC patients are similar. Patients exposed to DARA or CFZ have an improved survival compared to those who did not receive these drugs. ASCT is also associated with a superior survival over those who did not receive a transplant. Further studies are needed to evaluate the efficacy of these next-generation drugs in this patient population. Disclosures Martin: Janssen: Research Funding; Seattle Genetics: Research Funding; AMGEN: Research Funding; GSK: Consultancy; Sanofi: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Wong:Sanofi: Membership on an entity's Board of Directors or advisory committees; Fortis: Research Funding; Roche: Research Funding; Janssen: Research Funding; Amgen: Consultancy; GSK: Research Funding; Bristol Myers Squibb: Research Funding.

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Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽

10.1182/blood-2019-127237 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5880-5880

Author(s):

Nathan H Fowler ◽

Yanni Hao ◽

Stephen Lim ◽

Guifang Chen ◽

Frank Li ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Third Line ◽

Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

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