scholarly journals Risk Factors Associated with Earlier Relapse and Death and Treatment Response in Patients with Follicular Lymphoma in Taiwan

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5338-5338
Author(s):  
Sung-Nan Pei ◽  
Kuan-Chih Huang ◽  
Ming-Chung Wang ◽  
Ching-Yuan Kuo ◽  
Ming-Chun Ma ◽  
...  
Keyword(s):  
Risk Factors ◽  
Follicular Lymphoma ◽  
Disease Stage ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Factors Associated ◽  
Β2 Microglobulin ◽  
Tertiary Center ◽  
Equity Ownership

Abstract Background: Follicular Lymphoma (FL) has been relatively uncommon in Asia. Information on prognostic risk factors are scarce in the Asian population. We evaluated patients with FL in a tertiary medical center in Taiwan to gain better understanding of real world treatment and risk factors affecting outcome. Purpose: To evaluate clinical outcomes and risk factors associated with outcome in patients with FL in Taiwan. Methods: We conducted a retrospective cohort study using electronic medical records from Kaohsiung Chang Gung Memorial Hospital, a major regional hospital in southern Taiwan, from 01 January 2008 to 31 December 2017. Newly diagnosed patients with FL were enrolled from 01 Jan 2008 to 31 Dec 2013. All eligible patients were followed-up until study end, loss to follow-up or until death, whichever occurred first. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Risk factors of EFS and OS were identified using Cox proportional hazards model. A significant association was set at p<0.01. Results: A total of 67 patients with newly diagnosed FL were included in the cohort analysis, accounting for 13.7% (67/489) patients with B cell non-Hodgkin lymphoma during the enrolment period. Median follow-up time was 60 months. At diagnosis, median age was 58 years (range 28-95), 56.7% (38/67) of patients were female, and 68.7% (46/67) had Stage III-IV disease. There were 37.3% (25/67) of patients with bone marrow involvement and 22.4% (15/67) with involvement of more than one extra-nodal site. The percentage of patients with low, intermediate and high-risk FL was 32.8%, 25.4%, 38.8%, respectively by FLIPI-1, and 13.4%, 44.8%, 26.9% by FLIPI-2. 72% (48/67) of patients received first-line treatment with regimens that included rituximab, cyclophosphamide, vincristine, prednisolone ± doxorubicin. Of these, 54.2% (26/48) of patients demonstrated complete response and 37.5% (18/48) had a partial response. A further 22.4% (15/67) patients received other treatments and 6.0% (4/67) patients did not receive any treatment. Progression of disease within 24 months after commencing treatment occurred in 32.8% of patients. The 5-year EFS and OS for all patients were 48.6% and 76.2%, respectively (Figure). A higher relapse rate was associated with the presence of B symptoms (HR 6.1; 95% confidence interval [CI] 2.8-13.2), ECOG score ≥2 (HR 5.7; 95% CI 1.7-19.6), FLIPI-2 score ≥3 (HR 5.5; 95% CI 1.4-20.6), large cell transformation (HR 4.1; 95% CI 1.66-10.6), elevated β2 microglobulin (HR 4.0; 95% CI 1.8-9.1), age >70 years (HR 3.6; 95% CI 1.7-7.5), involvement of more than one extra-nodal site (HR 3.5; 95% CI 1.6-7.6) and elevated LDH (HR 2.5; 95% CI 1.3-5.1) (Table 2). Conclusion: Most patients with FL in this tertiary center in Taiwan were at an advanced disease stage at diagnosis. While the majority responded to conventional chemotherapy, one-half of patients progressed within 5 years. Involvement of extra-nodal sites, B symptoms, older age (>70) higher FLIPI-2 score, elevated β2 microglobulin and ECOG score ≥2 were identified as risk factors for earlier relapse and death. Disclosures Pei: Janssen Research & Development, LLC: Research Funding. Huang:Janssen Research & Development, LLC: Employment. Rothwell:Janssen Research & Development, LLC: Employment, Equity Ownership. Qiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Liu:Janssen Research & Development, LLC: Employment, Equity Ownership.

scholarly journals Health Resource Utilization and Costs Associated with the Use of Obinutuzumab-Based Regimens Are Similar to Rituximab-Based Regimens for the First-Line Treatment of Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4721-4721
Author(s):  
Tu My To ◽  
Keith L. Dawson ◽  
Anthony S Masaquel ◽  
Arpamas Seetasith
Keyword(s):  
Drug Treatment ◽  
Follicular Lymphoma ◽  
Real World ◽  
Specific Drug ◽  
First Line ◽  
Employment Equity ◽  
Total Cost ◽  
Claims Database ◽  
Equity Ownership

Introduction: Obinutuzumab (GA101; G), a fully humanized, glycoengineered, type II anti-CD20 monoclonal antibody, is approved in the US for the first-line (1L) treatment of follicular lymphoma (FL). Despite the superior efficacy of G plus chemotherapy (G-chemo) versus rituximab (R) plus chemotherapy (R-chemo) in patients with previously untreated FL demonstrated in the Phase III, randomized GALLIUM study (NCT01332968; Marcus et al. N Engl J Med 2017), information on healthcare resource use (HRU) and real-world costs with G in previously untreated FL patients is limited. The aim of this retrospective cohort study was to examine HRU and costs for G-based and R-based therapies for the 1L treatment of FL using a US claims database. Methods: The data source for this study was the PharMetrics Plus Commercial Claims database. Adult patients (≥18 years) diagnosed with FL between February 1, 2015 and September 30, 2018 and who began any treatment for FL between February 1, 2016 and September 30, 2018 were included. The first FL treatment date within this selection window was denoted the index date. Patients were required to have ≥12 months of pre-index and ≥3 months of post-index continuous study enrolment, and to have at least one FL diagnosis on or during the 12-month pre-index period. Patients with FL treatment during the 12-month pre-index period were excluded in order to select only previously untreated patients. HRU and cost data during the 1L treatment period were descriptive and categorized by HRU category. Costs are in 2018 US dollars ($) and standardized as per patient per month (PPPM) costs. FL treatment determination was based on National Comprehensive Cancer Network guidelines. Results: A total of 1584 FL patients with ≥3 months follow up were analyzed. Overall, 26 patients received G-chemo (any combination) as their 1L treatment, 208 patients received R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), 391 patients received R-Benda (bendamustine) and 17 patients received R-CVP (cyclophosphamide, vincristine, prednisone); the remaining 942 patients received other regimens (predominantly other R combinations). Data are reported for those patients who received G-chemo, R-CHOP, R-Benda or R-CVP as 1L therapy (n=642; 281 females, 361 males). Baseline patient characteristics were similar for most variables across treatment groups. Mean (standard deviation [SD]) age was 56.9 (9.7) years and all patients had a Charlson Comorbidity Index (CCI) of ≥2 (mean [SD]: 2.9 [1.9]). Mean (SD) patient follow-up was 14.1 (8.0) months and mean (SD) duration of 1L treatment was 7.0 (5.1) months. A summary of all-cause HRU in patients receiving 1L treatment is provided by treatment category (Figure 1A). The proportion of patients with at least one hospitalization was highest with R-CHOP (23.6%). The proportion of patients with at least one emergency room (ER) visit was highest with R-Benda (29.4%). Mean (SD) total all-cause healthcare costs PPPM during 1L treatment were comparable among G-chemo, R-CHOP and R-Benda (Figure 1B) and lowest with R-CVP ($17,874 [$13,465]). Medical costs (mean [SD]) were highest for R-Benda ($27,716 [$19,610] PPPM) and lowest for R-CVP ($17,373 [$12,908] PPPM). G-chemo was associated with the lowest pharmacy costs ($76 [$107] PPPM) (Figure 1B). Mean (SD) total cost of FL drug treatment PPPM was $16,028 ($9,942) for G-chemo, $11,684 ($6,122) for R-CHOP and $12,108 ($8,794) for R-CVP. Mean (SD) total cost of FL drug treatment PPPM was highest with R-Benda ($21,263 [$15,328]). G-specific drug costs PPPM ($9,643 [$6,071]) were similar to R-specific drug costs ($9,992 [$5,234] R-CHOP; $9,083 [$5,859] R-Benda; and $10,702 [$7,717] R-CVP). Conclusions: Our results depict real-world HRU and costs associated with G and commonly used 1L regimens for FL. In this setting, HRU and costs associated with G-chemo were comparable with R-chemo, supporting the use of G-chemo as a treatment option for patients with previously untreated FL. The study findings are limited by the small sample size of the G-chemo patient cohort (n=26) and short follow-up; to address this, an updated analysis incorporating a larger number of patients is planned. Disclosures To: Genentech, Inc.: Employment, Equity Ownership. Dawson:Roche/Genentech: Equity Ownership; Genentech: Employment. Masaquel:Genentech: Employment; Roche: Equity Ownership. Seetasith:Genentech: Employment, Equity Ownership.

Clinical Outcomes of Patients with Newly Diagnosed Multiple Myeloma Receiving Triplet Therapy in the Connect MM® Disease Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4229-4229
Author(s):  
Jatin J. Shah ◽  
Rafat Abonour ◽  
Mohit Narang ◽  
Jayesh Mehta ◽  
Howard R. Terebelo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Equity Ownership ◽  
Triplet Regimen

Abstract Introduction: Triplet therapies are used for treatment (Tx) of both transplant-eligible and -ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Actual patterns and outcomes of Tx are not fully understood. Connect MM® is the first and largest multicenter, US-based, prospective observational cohort study designed to characterize Tx patterns and outcomes for pts with NDMM. This analysis describes demographic and disease characteristics of pts who received triplet Tx as an induction regimen and for whom transplant was or was not intended. The analysis explores the relationship of these factors with overall survival (OS) and other efficacy endpoints. Patients and Methods: Pts aged ≥ 18 y with NDMM within 60 days of diagnosis were eligible for enrollment regardless of disease severity, medical history, or comorbidities. Data including transplant intent (yes/no) was collected at baseline; follow-up data was collected quarterly thereafter. Based on the initial intent, 2 groups were identified: patients with intent to transplant who received transplant (TT) and pts with no intent to transplant who did not receive a transplant (NT). Triplet Tx was defined as the combination of ≥ 3 concurrent therapeutic agents in the first course of Tx (within 56 days of study entry). KM analysis adjusted for age was conducted for OS. Because decisions on use of transplant and triplet therapy are influenced by multiple factors, a multivariable Cox regression analysis was performed to evaluate the contribution of the triplet therapy (yes/no) to OS and was adjusted for other variables, including age, comorbidities, and ISS staging. Results: Between September 2009 and December 2011, 1493 pts were enrolled. This analysis was on 1436 pts: 650 pts with transplant intent and 786 pts without transplant intent. The data cutoff date was November 30, 2014, and the median follow-up for overall survival (OS) was 33.8 mos. Of pts with transplant intent, 451 (69%) received transplant (TT) and 199 (31%) did not. Of pts without transplant intent, 62 (8%) received transplant and 724 (92%) did not (NT). The abstract focuses on TT and NT groups only. NT pts tended to be older and have more advanced ISS staging and higher β2-microglobulin levels than TT pts (Table). The most common triplet regimen given during the first course treatment (within 56 days) was lenalidomide, bortezomib, and dexamethasone (RVd). RVd was administered to 34% of the NT pts (76/225) and 59% of the TT pts (152/257). The most common non-triplet regimen was bortezomib and dexamethasone (Vd), which was given to 31% of NT pts (156/499) and 38% of TT pts (73/194). Within the NT group, pts given triplet Tx had a lower risk of death than those who did not receive triplet Tx (P = .0013). The multivariable analysis found triplet Tx to be associated with a 36% reduced risk of death (hazard ratio [HR] = 0.64 [95% CI, 0.50-0.82]; P = .001). ISS disease stage (HR = 1.43 [95% CI, 1.21-1.69]; P < .001) and history of diabetes (HR = 1.38 [95% CI, 1.08-1.78]; P = .012) were negative prognostic factors for OS. Within the TT group, pts who received triplet Tx did not attain an OS benefit (P = .8993), and no baseline characteristics were significantly associated with OS. These results may be limited by other factors not considered that may have influenced physicians' choice of treatment, including the use of maintenance therapy and a short follow-up period of 33.8 months. Conclusions: Triplet Tx as a first regimen is associated with longer OS in pts without transplant intent who did not receive a transplant. RVd and Vd were the most common first Tx regimens, respectively. Continued follow-up of these pts and enrollment of an additional cohort will provide additional data with mature follow-up. Table 1. Table 1. Disclosures Shah: Bristol-Myers Squibb: Research Funding; Array: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Research Funding, Speakers Bureau. Narang:Celgene: Speakers Bureau. Mehta:Celgene Corporation: Speakers Bureau. Terebelo:Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacylics: 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. Gasparetto:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Honoraria, Other: Export Board Committee, Speakers Bureau. Toomey:Celgene: Consultancy. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Srinivasan:Celgene Corporation: Employment, Equity Ownership. Larkins:Celgene Corporation: Employment, Equity Ownership. Nagarwala:Celgene Corporation: Employment, Equity Ownership. Rifkin:Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; 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.

scholarly journals Evaluation of Cardiovascular Disease Risk in Chronic Myelogenous Leukemia Patients Using Electronic Medical Records from Community-Based Oncology Practices in the United States

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4478-4478
Author(s):  
Anna O. D'Souza ◽  
Dinara Makenbaeva ◽  
Eileen Farrelly ◽  
Pamela Landsman-Blumberg ◽  
Bjorn Bolinder
Keyword(s):  
Risk Factors ◽  
Research Funding ◽  
Adult Population ◽  
Myelogenous Leukemia ◽  
Cvd Risk ◽  
Community Based ◽  
Employment Equity ◽  
Equity Ownership ◽  
The U.S

Abstract PURPOSE: Current guidelines (Version I.2015) from the National Cancer Comprehensive Network recommend that patient's comorbidities, including cardiovascular disease (CVD), be taken into consideration when evaluating tyrosine kinase inhibitor (TKI) therapy options for chronic myelogenous leukemia (CML). The guidelines also recommend using certain TKIs "with caution in patients with cardiovascular risk factors" and evaluating patients "for vascular risk factors prior to initiating and during treatment." Recent research has evaluated the prevalence of CVD in the CML patient population, but there is a lack of published data on the risk of developing CVD in this population. The study purpose was to assess the risk for CVD among CML patients using an oncology-based electronic medical record (EMR) database. METHODS: A retrospective cohort analysis was conducted using data from the International Oncology Network (ION) EMR Database (01/2005 to 01/2015) of patients treated by community-based oncologists in the U.S. The study population included patients with a diagnosis of CML (ICD-9 CM: 205.1) aged 18 years and older, having no other primary cancer or acute myeloid leukemia, and not enrolled in a clinical trial anytime during the study period. Study index was the date of the first observed CML diagnosis during 01/2005 to 10/2014. Prevalence of CVD and its risk factors were estimated for baseline and during a follow-up of up to 5 years. Baseline included all available medical information prior to and on the index date. CVD and its risk factors were defined as in the Framingham Heart Study, and were identified using diagnoses and/or treatment as applicable from pre-defined fields in standard EMR tables or through electronic text search of the physician progress notes available in the database. The Framingham risk score for CVD was computed at baseline using age, gender, smoking status, hypertension, dyslipidemia, and diabetes. To compare with annual estimates from the U.S. general population, all prevalence estimates at 1 year for the CML population were age and gender standardized to the U.S. 2010 census population aged 20 and older. Standardized rate ratios and z-tests were computed to assess the magnitude and significance, respectively, of the differences in annual rates between CML patients and the general U.S. population. RESULTS: A total of 1,639 CML patients were included with mean±SD and median follow-up time (in years) of 2.4±1.7 and 2.1, respectively. Average age was 59±16 and 52.2% were male. CVD was present in 18.7% of patients at baseline. On average, CML patients without CVD at baseline had a Framingham CVD risk score of 12.8% compared to 8.7% in the general US adult population without CVD and nearly 44% of CML patients without CVD were at intermediate to high risk (>10%). Among patients without CVD, in the 5-year follow-up period 77.7% had at least 1 CVD risk factor up from 52.7% at baseline. Relative to the general U.S. adult population, annual standardized prevalence rates in CML patients were 20%, 30%, and 40% higher for hypertension, diabetes and obesity, respectively, while being 20% and 60% lower for dyslipidemia and smoking. In the 5-year follow-up period, the prevalence of CVD in the study sample rose to 33.0% of the sample of patients available at 5 years. Annual standardized prevalence rates of myocardial infarction, atherosclerosis, and heart failure was 2.7 to 3.5 times higher (p<0.001) relative to the general U.S. adult population. CONCLUSION: This study suggests that CML patients may have both a higher risk and prevalence of CVD compared to the general U.S. adult population, likely due to several contributing factors which should be evaluated in further research. Given the chronic nature of CML and the need for long term TKI treatment, it is important to regularly evaluate and monitor patients for CVD and its risk factors. Disclosures D'Souza: Xcenda: Research Funding. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Farrelly:Xcenda: Research Funding. Landsman-Blumberg:Xcenda: Research Funding. Bolinder:Bristol-Myers Squibb: Employment, Equity Ownership.

Nilotinib Versus Imatinib in Patients (pts) with Newly Diagnosed Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENESTnd 36-Month (mo) Follow-up

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 452-452 ◽  
Author(s):  
Giuseppe Saglio ◽  
Philipp D. LeCoutre ◽  
Ricardo Pasquini ◽  
Saengsuree Jootar ◽  
Hirohisa Nakamae ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Philadelphia Chromosome ◽  
Safety Data ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Abstract 452FN2 Background: In ENESTnd, pts treated with nilotinib demonstrated higher and faster rates of major molecular response (MMR, ≤ 0.1% BCR-ABLIS), deeper molecular response (MR4, ≤ 0.01%IS and MR4.5, ≤ 0.0032%IS), and complete cytogenetic responses (CCyR) along with significantly lower rates of progression to AP/BC and fewer CML-related deaths compared with imatinib by 12 and 24 mo. Here, we report data with a minimum follow-up of 24 mo; however, efficacy and safety data based on considerably longer follow-up of ≥ 36 mo will be presented. As demonstrated in IRIS and other imatinib trials, most pts who progress on imatinib do so within the first 3 years of therapy. Thus, this 36-mo update of ENESTnd will be important to further verify the benefits of nilotinib in newly-diagnosed pts. Methods: 846 adult pts with newly-diagnosed Ph+ CML-CP were randomized to nilotinib 300 mg twice daily (BID) (n = 282), nilotinib 400 mg BID (n = 281), or imatinib 400 mg once daily (QD) (n = 283). MMR, MR4, MR4.5, time to progression to AP/BC on treatment, progression-free survival (PFS) on treatment, and overall survival (OS) were evaluated. Results: By 24 mo, both doses of nilotinib demonstrated significantly higher rates of MMR, MR4, and MR4.5 vs imatinib (Table). Nilotinib-treated pts achieved median BCR-ABLIS levels of 0.09% (300 mg BID) and 0.10% (400 mg BID) by 12 mo, while this level of reduction was not observed before 24 mo on imatinib. More pts with CCyR achieved MMR at 12 and 24 mo with either dose of nilotinib vs imatinib (Table). Regardless of Sokal risk, rates of MMR and MR4.5 were higher for nilotinib at both doses vs imatinib (Table). Progression to AP/BC (excluding clonal evolution [CE]) on treatment was significantly lower for nilotinib vs imatinib (2 pts and 3 pts with nilotinib 300 mg BID [P = .0059] and 400 mg BID [P =.0196]), respectively vs 12 pts with imatinib). After achieving CCyR, 4 pts treated with imatinib progressed to AP/BC and 2 pts treated with nilotinib 400 mg BID progressed after achieving both CCyR and MMR (1 also achieved MR4). No pt who achieved MR4.5 progressed at any time. All but 1 pt who progressed to AP/BC on treatment were in the intermediate and high Sokal risk groups; 1 pt treated with nilotinib 400 mg BID progressed in the low Sokal risk group who had an E255V mutation at progression. When considering progression events of pts after discontinuation of treatment, an additional 7, 2, and 6 events (excluding CE) were observed with nilotinib 300 mg BID, nilotinib 400 mg BID and imatinib, respectively. Twice as many pts had emergent mutations on imatinib (n = 20) vs nilotinib (n = 10 on 300 mg BID; n = 8 on 400 mg BID). At 24 mo, OS remained similar in all groups, but there were fewer CML-related deaths in both nilotinib 300 mg BID (5 pts) and nilotinib 400 mg BID (3 pts) arms vs imatinib (10 pts). Both drugs were well tolerated and few new adverse events (AEs) and lab abnormalities were observed between 12- and 24-mo of follow-up. Nilotinib 300 mg BID had the fewest discontinuations due to AEs/lab abnormalities (9% vs 13% and 10% with nilotinib 400 mg BID and imatinib, respectively). Conclusions: With a minimum follow-up of 24 mo, nilotinib continued to demonstrate superiority vs imatinib with faster and deeper molecular responses and a significantly decreased risk of progression. These data support the use of nilotinib as a standard of care option in newly-diagnosed adult pts with Ph+ CML-CP. Disclosures: Saglio: Novartis Pharmaceutical: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Pfizer: Consultancy. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. LeCoutre:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria. Pasquini:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Nakamae:Novartis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau. Flinn:nOVARTIS: Research Funding. Hochhaus:Novartis Pharmaceutical: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding. Hughes:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Larson:Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding. Hoenekopp:Novartis Pharmaceutical: Employment, Equity Ownership. Gallagher:Novartis: Employment. Yu:Novartis: Employment, Equity Ownership. Blakesley:Novartis Pharmaceutical: Employment. Kim:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Novartis: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; BMS: Research Funding.

scholarly journals Prevalence and Predictors of Renal Impairment Among Patients with Multiple Myeloma (MM): An Analysis of Oncology Clinic Electronic Health Records Linked to Commercial Claims in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5657-5657
Author(s):  
Geoffrey Block ◽  
Alan Fu ◽  
Sally Wade ◽  
Renee Jaramillo ◽  
Sumita Bhatta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Function ◽  
Renal Impairment ◽  
Cox Model ◽  
Employment Equity ◽  
Health Records ◽  
Stage 4 ◽  
Equity Ownership ◽  
Increase In Risk

Abstract Background Although incurable, MM is responsive to treatment, and the prognosis of MM patients has improved dramatically over the past two decades. This has led to increased recognition of the importance of effective long-term management of the classic clinicopathological features of MM. Renal impairment (RI) is a defining hallmark of active myeloma. While it is known that RI is associated with poor survival and can complicate drug dosing and limit treatment options, patterns of renal function and risk factors of RI in MM are poorly characterized. This study seeks to characterize the natural history and risk factors of RI in MM using a unique real-world dataset that links patient-level electronic health records (EHR) to healthcare insurance claims. Methods The Oncology Services Comprehensive Electronic Records (OSCER) database contains EHR data from community and hospital-affiliated oncology clinics in the U.S. The MarketScan (MS) database contains healthcare claims information from large employers, managed care organizations, Medicare, and Medicaid programs. This study used a subset of MM patients with overlapping data from OSCER and MS, allowing the analysis of EHR-based serum creatinine and claims-based comorbidity data in the same patient. Patients ≥ 18 with a MM diagnosis between 2011 and February 28, 2016 in an OSCER clinic; had at least 6 months of continuous MS benefits coverage; no MM diagnosis in MS in the 3 months prior to OSCER MM diagnosis; and no evidence of another malignancy prior to MM diagnosis were included in the study. Index date was the date of OSCER MM diagnosis and patients were followed up until February 28, 2017. Baseline (BL) patient characteristics and potential risk factors of RI, including demographics, BMI, ECOG, ISS stage, and comorbidities (e.g., hypertension, diabetes, hypercalcemia, etc.) were assessed in the 6 months prior to index. Intravenous bisphosphonate (IV BP) use was assessed during follow-up. Renal function was assessed using the MDRD eGFR method or CKD stage diagnosis codes, with RI defined in this study as eGFR < 60 or stage 3+ CKD. BL eGFR was assessed using the serum creatinine measurement closest to the index in the interval 1 month before and 1 month after index. The prevalence of RI in the year following diagnosis was calculated based on the average number of at-risk patients during this period. Change in renal function for up to 4 years post-diagnosis was assessed by BL renal function and was characterized based on the worst recorded estimate of renal function during this period. A multivariate Cox model was used to assess the impact of BL risk factors and IV BP use during follow-up on progression to RI in patients without RI at BL (eGFR ≥ 60 and CKD diagnosis). Follow-up IV BP use (dose count) was treated as a time-dependent variable. Results The median number of eGFR values recorded per patient during follow-up was 18 (range: 7-36). Among newly diagnosed MM patients (n = 625), 69% (95% CI: 65-73%) experienced ≥ 1 episodes of eGFR < 60 ml/min or stage 3+ CKD diagnosis (RI) within 1 year of diagnosis, with 16% (13-20%) experiencing an episode of eGFR 15-29 or stage 4 CKD and 15% (11-18%) experiencing an episode of eGFR < 15 or stage 5 CKD. Among patients without RI at diagnosis (n = 281), 37% (31-43%) subsequently experienced at least one episode of RI during follow-up (Figure 1). In addition, 26% (20-32%) of patients with BL eGFR 30-59 or stage 3 CKD experienced progression to an episode of eGFR < 30 or stage 4+ CKD, and 31% (20-42%) of patients with BL eGFR 15-29 or stage 4 CKD progressed to an episode of eGFR < 15 or stage 5 CKD. In our multivariate Cox model, use of the IV BP zoledronic acid (ZA) during follow-up; ECOG; baseline eGFR; known predisposing conditions, including autoimmune diseases, vascular conditions, and infections of the kidney were found to be associated with higher risk for experiencing an episode of RI in patients with high BL renal function (Figure 2). In our sample, 12 doses of ZA was associated with a 2.4-fold (1.2-4.8) increase in risk of RI. A baseline ECOG of 1 vs. 0 was also associated with a 2.4-fold (1.1-5.2) increase in risk of RI. Conclusions Using a unique EHR-insurance claims linked data source, we found that two-thirds of patients experienced at least one episode of renal impairment within the first year of MM diagnosis. Repeated exposure to zoledronic acid and poor performance status may increase the risk of RI in patients without renal impairment at diagnosis. Disclosures Block: Amgen, Inc.: Consultancy. Fu:Amgen: Employment, Equity Ownership. Wade:Wade Outcomes Research and Consulting: Employment, Equity Ownership. Jaramillo:Amgen, Inc.: Consultancy; SimulStat: Employment. Bhatta:Amgen, Inc.: Employment, Equity Ownership. Raskin:Amgen, Inc.: Employment, Equity Ownership. Hernandez:Amgen, Inc.: Employment, Equity Ownership.

scholarly journals Quality-Adjusted Survival for Low-Dose Cytarabine (LDAC) Versus Glasdegib+LDAC Among Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Not Candidates for Intensive Chemotherapy: A Q-TWiST Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2610-2610 ◽  
Author(s):  
Youngmin Kwon ◽  
Timothy J Bell ◽  
Caitlyn Solem ◽  
Joseph C Cappelleri ◽  
Courtney Johnson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Equity Ownership ◽  
Relative Gains ◽  
Mean Time ◽  
Low Dose Cytarabine

Introduction: The efficacy and safety of glasdegib (a selective oral inhibitor of hedgehog signaling pathway) in combination with low-dose cytarabine (LDAC) was evaluated in a randomized, phase 2 trial of newly diagnosed acute myeloid leukemia (AML) patients (BRIGHT AML 1003; NCT01546038). Patients receiving glasdegib+LDAC experienced statistically significant and meaningful gains in overall survival (OS) compared with patients receiving LDAC alone (median OS [95% CI]): 8.3 months [4.7-12.2] vs 4.3 months [1.9-5.7]). This analysis examined whether quality-adjusted survival improvements were similarly observed using a quality-adjusted time without symptoms of disease progression or toxicities (Q-TWiST) approach to evaluate possible trade-offs between time with adverse events (toxicities), time in relapse/progression (i.e., with symptoms of disease), and 'good' survival (i.e., time without toxicities or symptoms of progression [TWiST]) when comparing regimens. Methods: OS in BRIGHT AML 1003 data, restricted to a follow-up of 20 months, was partitioned into time with toxicity (TOX: grade 3+ adverse events prior to progression), TWiST, and time post-progression (REL). Progression was defined as treatment discontinuation due to insufficient clinical response or death; patients who discontinued for other reasons (including adverse events) were censored at the date of discontinuation unless death occurred within 28 days of discontinuation. Q-TWiST was calculated by multiplying restricted mean time in each state by respective utilities (U) and then summing up the utility-adjusted time. Base case analysis used U(TOX)=U(REL)=0.5 and U(TWiST)=1.0; threshold analyses were performed varying U(TOX) and U(REL) jointly each from 0 to 1. Relative gains in Q-TWiST (i.e., Q-TWiST difference (combination vs LDAC) / OS in LDAC arm) of ≥15% were considered clearly clinically meaningful per the clinical literature. Sensitivity analysis varied the length of follow-up and AE definitions; subgroup analyses were also performed. 95% confidence intervals were obtained using the bootstrap procedure. Results: At 20 months of follow-up, the survival rate for glasdegib+LDAC and LDAC arm was 28.2% and 7.9%, respectively. Glasdegib+LDAC patients (n=78) compared with LDAC patients (n=38) had significantly longer mean time in TWiST (+3.4 [95% confidence interval: 1.8, 5.2] months) and TOX (+0.8 [0.1, 1.6] months), and longer but non-significant REL (+0.3 [-1.9, 2.3] months). Q-TWiST was 4.0 [2.1, 5.8] months longer for glasdegib+LDAC, translating into a 75% relative improvement in quality-adjusted survival relative to LDAC alone. In threshold analyses, absolute and relative Q-TWiST gains ranged from 3.5 to 4.5 months and 66% to 85%, respectively (Table 1). They exceeded the clinically meaningful threshold for gains in Q-TWiST and were statistically significant across all combinations of U(TOX) and U(REL). Results were robust to length of follow-up 6 to 24 month and remained significant when including all adverse events regardless of grade. Discussions/Conclusions: Glasdegib+LDAC is an add-on therapy that has demonstrated significant survival benefits for newly diagnosed AML patients who are unable to receive intensive chemotherapy. While patients can experience a longer time with toxicities from receiving glasdegib+LDAC (as expected since it is given as an add-on therapy), the trade-off can still be favorable as the treatment provides added time spent in 'good' health (i.e., a significantly longer time in TWiST). In the BRIGHT AML 1003 cohort, the relative gains in OS greatly exceeded previously established thresholds for being clearly clinically meaningful, which suggests that the benefits of glasdegib+LDAC vs LDAC alone outweigh the risks. Table 1 Disclosures Kwon: Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bell:Pfizer Inc.: Employment, Equity Ownership. Solem:Pharmerit International: Employment; Pfizer Inc.: Research Funding. Cappelleri:Pfizer: Employment, Equity Ownership. Johnson:Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bhattacharyya:Pfizer Inc: Employment, Equity Ownership. Hoang:Pfizer Inc.: Employment, Equity Ownership. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; BiolineRx: Consultancy; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

Astarabine, a Pro-Drug of Cytarabine, Is Safe for Patients with Advanced Acute Leukemia. A Phase I/IIa Single Center Study in Relapsed/Refractory or Medically Unfit Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3810-3810
Author(s):  
Tsila Zuckerman ◽  
Ruth Ben Yakar ◽  
Stela Gengrinovitch ◽  
Ron Hoffman ◽  
Israel Henig ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Intensive Therapy ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Targeted Killing ◽  
Secondary Aml ◽  
Unfit Patients ◽  
Equity Ownership ◽  
Refractory Aml

Abstract Introduction: Therapy of acute leukemia has not changed significantly over the years. Both acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) typically present or have a second peak in older adults, which often precludes intensive therapy due to associated comorbidities. Astarabine, a construct of cytarabine covalently bound to asparagine, is a pro-drug specifically targeting leukemic blasts which are dependent on an external source of asparagine. Within the blasts, Astarabine is cleaved to cytarabine enabling targeted killing and relative sparing of normal hematopoiesis. As such, Astarabine may serve as an ideal therapy for leukemia and, particularly, for medically unfit/older adults otherwise given only supportive therapy. Additionally, targeted killing by Astarabine may be more efficacious and can lead to improved responses in relapsed/refractory patients. The aim of this study was to evaluate the safety and optimal dose of Astarabine in refractory/relapsed or medically unfit patients with acute leukemia. Methods: This prospective open label study enrolled patients >18 years of age with relapsed/refractory acute leukemia or those unfit for intensive therapy, as judged by the treating physician. Refractory acute leukemia was defined as a failure to achieve remission following the last administered treatment. Relapsed disease was defined as recurrence after induction and consolidation. The study was approved by the Rambam IRB. Patients were enrolled into 4 Astarabine escalating dose cohorts, each composed of 3 patients. Treatment was administered as a 1-hour single daily infusion for 6 days. Astarabine doses for each infusion, measured as an equivalent to cytarabine dosing, for age ≤50 years were: 0.5g/m2, 1.5g/m2, 3g/m2 and 4.5g/m2. Astarabine doses for age >50 years were reduced by 50%. Results: The outcome of the first 3 cohorts (9 patients) is reported herein (table 1). Eight patients had AML, of whom 4 had refractory/relapsed and 4 had newly diagnosed secondary AML unfit for intensive therapy, while 1 patient had newly diagnosed ALL. Median age was 80 years (range 27-90). Four patients are alive with a follow-up of 1-10 months, 2 of whom are in continuous CR 4 and 6 months after treatment. Three patients died from disease progression; one died suddenly 7 days after treatment, an event not judged to be treatment-related. No significant adverse events were recorded during or after therapy apart from neutropenic fever. Conclusions: Astarabine, a pro-drug of cytarabine, is safe and very well tolerated, including patients over 80 years of age, and resulted in complete remission in 3 of 9 patients with acute leukemia. Further dose escalation studies are currently ongoing at a cytarabine-equivalent dose of 4.5 g/m2. A phase II study is planned to confirm these encouraging results and define the use of Astarabine for patients otherwise unable to receive high doses of cytarabine. Table 1. Patient No. Age in years Diagnosis BM blasts after treatment Outcome Follow-up duration in months Day 14 Day 30 1 75 Refractory AML 90% 83% Died- DP 3 2 81 Refractory AML 64% 70% Died - DP 2 3 27 Refractory AML 37% 60% Alive with disease 6 4 76 Secondary AML 39% 63% Died -DP 4 5 81 Secondary AML 5% 0% Alive in CR 6 6 63 Refractory AML 100% 100% Died -DP 1 7 90 ALL 3% 0.2% Alive in CR 4 8 86 Secondary AML 80% 8% Alive in PR 3 9 80 Secondary AML N/A N/A Died 1 DP: disease progression; PR: partial remission; CR: complete remission; N/A: non-applicable Disclosures Off Label Use: Astarabine, a Pro-Drug of Cytarabine. A noval therapy for acute leukemia. Ben Yakar:BioSight Ltd.: Employment, Equity Ownership. Gengrinovitch:BioSight Ltd.: Employment, Equity Ownership, Patents & Royalties.

scholarly journals Bosutinib Vs Imatinib for Newly Diagnosed Chronic Myeloid Leukemia (CML) in the BFORE Trial: 18 Month Follow-up

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 896-896
Author(s):  
Carlo Gambacorti-Passerini ◽  
Michael W. Deininger ◽  
Michael J. Mauro ◽  
Charles Chuah ◽  
Dong-Wook Kim ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Primary Endpoint ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Grade 3

Abstract Introduction: Bosutinib is a potent SRC/ABL tyrosine kinase inhibitor approved for treatment of adults with CML resistant or intolerant to prior therapy. Here we compare the efficacy and safety of first-line bosutinib versus imatinib in patients with chronic phase (CP) CML enrolled in BFORE after ≥18 months of follow-up. Methods: BFORE (NCT02130557) is an ongoing, multinational, open label phase 3 study that randomized 536 patients 1:1 to 400 mg QD bosutinib (n=268) or 400 mg QD imatinib (n=268 [3 not treated]). The prespecified primary endpoint was major molecular response (MMR) rate at 12 months in the modified intent-to-treat (mITT) population, defined as Philadelphia chromosome‒positive (Ph+) patients with e13a2/e14a2 transcripts, and excluding Ph- patients and those with unknown Ph status and/or BCR-ABL transcript type (mITT: BOS, n=246; IM, n=241). Efficacy results refer to the mITT population unless otherwise noted. Results: MMR rate was higher with bosutinib versus imatinib at 18 months (56.9% vs 47.7%; P=0.042). Among all randomized patients (ITT) 18-month MMR rates were higher for bosutinib (56.7% vs 46.6%; P &lt;0.02). Earlier analyses (Table) showed complete cytogenetic response (CCyR) rate by 12 months (77.2% vs 66.4%; P=0.0075) was significantly higher with bosutinib versus imatinib. Rates of BCR-ABL1 transcript ratio ≤10% (International Scale) at 3 months (75.2% vs 57.3%), as well as MR4 at 12 months (20.7% vs 12.0%) and MR4.5 at 12 months (8.1% vs 3.3%), were all higher with bosutinib versus imatinib (all P &lt;0.025). By comparison at 18 months, rates of MR4 (24.4% vs 18.3%) and MR4.5 (11.4% vs 7.1%) were consistent with this trend. Also after ≥18 months follow-up, time to MMR (hazard ratio=1.36, based on cumulative incidence; P=0.0079) and time to CCyR (hazard ratio=1.33; P=0.0049) were shorter for bosutinib (Figure). Cumulative incidence of transformation to accelerated/blast phase disease at 18 months was 2.0% and 2.9% for bosutinb and imatinib, respectively, of which 2 bosutinib and 4 imatinib patients discontinued treatment due to transformation. Additional treatment discontinuations due to suboptimal response/treatment failure occurred in 11 (4.1%) and 35 (13.2%) of bosutinib and imatinib patients, respectively. Dose increases happened in 20% of bosutinib-treated and 31% of imatinib-treated pts There were 2 deaths and 9 deaths in the bosutinib and imatinib arms, respectively. One patient taking bosutinib died within 28 days of last dose, while 4 patients taking imatinib died with that period from last dose. Overall survival at 18 months was 99.6% vs. 96.6% for bosutinib and imatinib groups, respectively. Grade ≥3 diarrhea (8.2% vs 0.8%) and increased alanine (20.9% vs 1.5%) and aspartate (10.1% vs 1.9%) aminotransferase levels were more frequent with bosutinib. Cardiovascular, peripheral vascular, and cerebrovascular events were infrequent in both arms (3.4%, 1.9%, and 0.4% bosutinib vs 0.0%, 1.1%, and 0.8% imatinib; grade ≥3: 1.5%, 0%, and 0.4% vs 0%, 0%, and 0.4%). There were no deaths in the bosutinib arm and 1 death in the imatinib arm due to treatment-emergent vascular events. Treatment discontinuations due to drug-related toxicity occurred in 15.3% and 9.4% of bosutinib and imatinib patients, respectively. Conclusion: After 18 months of follow-up,the MMR benefit seen with bosutinib over imatinib was sustained. These results are in line with observations at 12 months where patients taking bosutinib had significantly higher response rates (primary endpoint) and achieved responses sooner than those on imatinib. Safety data were consistent with the known safety profiles. These results suggest that bosutinib may be an important treatment option for patients with newly diagnosed CP CML. Disclosures Gambacorti-Passerini: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Deininger: Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Celgene: Research Funding; BMS: Consultancy, Research Funding; Gilead: Research Funding; ARIAD: Consultancy; Ariad Pharmaceuticals, Bristol Myers Squibb, CTI BioPharma Corp, Gilead, Incyte, Novartis, Pfizer, Celgene, Blue Print, Galena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Mauro: Bristol-Myers Squibb: Consultancy. Chuah: Avillion: Honoraria; Chiltern: Honoraria; BMS: Honoraria, Other: Travel; Novartis: Honoraria. Kim: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Il-Yang: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Milojkovic: Novartis: Consultancy, Honoraria; Incyte: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. le Coutre: BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; ARIAD: Honoraria. García Gutiérrez: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Crescenzo: Pfizer: Employment, Equity Ownership. Leip: Pfizer: Employment, Equity Ownership. Bardy-Bouxin: Pfizer: Employment, Equity Ownership. Hochhaus: Novartis: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Ariad: Research Funding; MSD: Research Funding; BMS: Research Funding. Brümmendorf: Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Cortes: Sun Pharma: Research Funding; ARIAD: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Teva: Research Funding.

scholarly journals Treatment Patterns Among Newly Diagnosed Multiple Myeloma Patients in the United States Veteran Population (2010-2015)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5952-5952
Author(s):  
Kejal Parikh ◽  
Shivani Pandya ◽  
Safiya Abouzaid ◽  
Onur Baser ◽  
Lin Xie ◽  
...  
Keyword(s):  
Research Funding ◽  
Cox Regression ◽  
Treatment Patterns ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Chemotherapy Agent ◽  
The Us ◽  
Equity Ownership

Abstract Background: Despite a relatively higher incidence in the veteran population, there are few real-world claims-based analyses to describe Multiple Myeloma (MM) treatment patterns among this patient population (Landgren O, Blood, 2006). This study aimed to assess treatment patterns among newly diagnosed MM (ndMM) patients using the US Veteran Health Administration (VHA) data. Methods: This retrospective study identified adult patients with ≥2 claims for MM (ICD-9-CM code: 203.0x) 30 days apart and ≥1 treatment during identification period (1OCT2011-31MAR2015) from the VHA dataset. The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless patients died within 6 months (follow up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant (ASCT)), and no evidence of ASCT in the follow up period. A subsequent COT (COT2) was defined as the earliest occurrence of: the addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or a dose increase from maintenance to relapse therapy. Dexamethasone/prednisone[d] which were assumed to be included regardless of whether or not they were observed during the study period did not impact the ongoing COT. Treatment patterns during the follow-up period were initially examined among patients treated with novel (lenalidomide [R] and/or bortezomib [V] with or without chemotherapy agents) and non-novel therapies (≥1 chemotherapy agent, steroid monotherapy) and then compared among those initiating Rd and Vd. Time to next treatment (TTNT) was defined as the duration from initiation of COT1 plus any gaps before COT2. Kaplan Meier and Cox regression analyses were performed to evaluate TTNT and assess the impact of various predictors on TTNT among patients initiating Rd and Vd. Results: Of 1,183 patients that met the inclusion criteria, 55.4% (n=655) were treated with novel therapies and 44.6% (n=528) with non-novel therapies. Among patients treated with novel therapy, the majority initiated Rd (47.8%; n=313) as COT1 followed by Vd (31.2%; n=204), Vd with cyclophosphamide (11.5%; n=75), RVd (6.6%; n=43), Vd with a chemotherapy agent (2.4%; n=16) and Rd with a chemotherapy agent (0.6%; n=4).Rd initiators were significantly older (75.1 vs 70.6 years, p=0.0002) and a higher percentage was white (69.7% vs 47.0%; p<0.0001) than Vd treated patients. While the Charlson Comorbidities Index score did not differ between the two groups (3.6 vs 4.0, p=0.0583), a significantly higher percentage of patients treated with Vd had some comorbidities including hepatitis and renal disease. Among patients with laboratory tests, patients treated initially with Vd had lower hemoglobin (10.8 vs 11.4 g/dl, p=0.0012) and higher serum creatinine (2.3 vs 1.4 mg/dl, p<0.0001) during the pre-index period. The overall average treatment duration in COT1 was significantly longer among patients treated with Rd vs Vd (10.9 vs 7.0 months, p<0.0001). Among patients who were still on active COT1, the mean duration in COT1 was longer among patients treated with Rd than Vd (18.7 vs 13.3 months, p=0.0061). A significantly higher percentage of patients treated with Vd progressed to COT2 (52.5%, vs 26.2% p<0.0001) as compared to Rd. Among patients who progressed to COT2, those treated with Vd had a shorter TTNT compared to Rd (Mean: 9.3 vs 12.8 months, p=0.0049). After adjusting for baseline demographic and clinical factors using Cox regression, TTNT remained significantly shorter for Vd vs those treated with Rd (HR: 2.67, 95% CI: 1.9-3.7, p <0.0001). Conclusion: Slightly over half of MM patients in the US Veteran population were treated with a regimen containing novel therapies; Rd and Vd were the most commonly observed among these. Patients treated initially with Vd had a significantly shorter TTNT compared to those treated with Rd. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on Vd. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Baser:Celgene: Research Funding. Xie:Celgene: Research Funding. Patel:Celgene: Consultancy.

Ofatumumab (OFA) in Combination with CHOP for Previously Untreated Follicular Lymphoma: Follow-up Results

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1632-1632
Author(s):  
Myron S. Czuczman ◽  
Georg Hess ◽  
Ole Gadeberg ◽  
Lars Moeller Pedersen ◽  
Per Hansen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Abdominal Hernia ◽  
Employment Equity ◽  
End Points ◽  
Vulval Cancer ◽  
Equity Ownership ◽  
Hodgkin's Lymphomas

Abstract Abstract 1632 Background: OFA is a fully human monoclonal antibody that binds to both the large and small extracellular loops of CD20. OFA is currently approved for patients (pts) with refractory chronic lymphocytic leukemia and has demonstrated activity in non-Hodgkin's lymphomas, including follicular lymphoma (FL). We previously reported results of a phase II study of OFA in combination with CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg daily for 5 days) chemotherapy (O-CHOP) in pts with previously untreated FL (Czuczman et al. Br J Haematol. 2012;157:438). We now report updated efficacy, safety and pharmacokinetic (PK) follow-up data for this study. This trial is registered at www.clinicaltrials.gov (NCT00494780). Methods: Fifty-nine pts with previously untreated FL were randomized to OFA 500 mg (n = 29) or 1000 mg (n = 30) on day 1, with CHOP on day 3, every 3 weeks for 6 cycles. The primary end point was overall response rate (ORR), as assessed by an independent end points review committee. Secondary end points included complete response (CR), progression-free survival (PFS), overall survival, adverse events (AEs) and PK. Follow-up assessments after therapy were done every 3 months (mo) until mo 12 and then every 6 mo until alternative FL therapy or mo 60. Positron emission tomography (PET) was done at baseline and 3 mo after last therapy. Blood samples for PK analyses were collected to determine OFA serum concentrations, and noncompartmental methods were used to estimate PK parameter values. Results: Fifty-eight pts received therapy; 1 pt in the 1000-mg group withdrew before initiation of therapy. The ORR was 90% for the 500-mg group (n=29) and 100% for the 1000-mg group (n=29); 55% of pts achieved CR or unconfirmed CR (CRu), including 67% of pts with a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3–5. At baseline, 57 pts were PET positive, and 49 pts underwent repeat PET scans after therapy. Forty of 49 pts (82%) became PET negative, including 27 of 29 (93%) pts who achieved CR/CRu and 13 of 20 pts (65%) who achieved partial response (PR). With a median follow-up of 33.8 mo, the median PFS for the 500-mg group was 27.6 mo and the median PFS for the 1000-mg group was not reached (P=0.46). Median PFS for pts with FLIPI scores of 0–1 (n=17), 2 (n=20) and 3–5 (n=21) was not reached, 27.6 mo and 27.6 mo, respectively (P=0.68). Median PFS for pts (n=32) who achieved CR/CRu was also not reached and was 28.3 mo for pts (n=23) achieving PR. Median PFS for PR pts who were PET positive and PET negative after therapy was not reached and 28.3 mo, respectively. No deaths have been reported. No hematologic serious AEs (SAEs) were experienced during the follow-up period. During the follow-up period, non-hematologic SAEs were reported in 1 pt in the 500-mg group (pneumonia) and 5 pts in the 1000-mg group (abdominal hernia, erysipelas, intervertebral disc protrusion, meniscus lesion and vulval cancer); none were ofatumumab-related. After repeated dosing, OFA clearance values were 6.3 and 5.9 mL/h, and half-life values were 27.2 and 26.8 days in the 500-mg and 1000-mg groups, respectively. Conclusions: O-CHOP achieved durable remissions in previously untreated pts with FL. There were no observed PK or PFS differences between the 500-mg and 1000-mg arms, but the study was not powered to detect such differences. O-CHOP was effective in pts with high-risk FLIPI scores, and CR/CRu and PFS rates were not affected by FLIPI score. PET status after therapy did not predict PFS in responding pts, although the study was too small to make such a determination. These results indicate that O-CHOP should be studied as a therapy for FL pts with high-risk FLIPI scores. Disclosures: Czuczman: GlaxoSmithKline: Advisory board Other, Honoraria. Off Label Use: Ofatumumab in follicular lymphoma. Belada:GlaxoSmithKline: Research Funding. Mayer:Roche: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding. Gupta:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Employment, Equity Ownership. Winter:GlaxoSmithKline: Employment, Equity Ownership. Goldstein:GlaxoSmithKline: Employment, Equity Ownership. Jewell:GlaxoSmithKline: Employment, Equity Ownership. Lisby:Genmab: Employment, Equity Ownership.

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