Real Life Treatment Alterations of Frontline Therapies in Classic Hodgkin's Lymphoma

Introduction Classic Hodgkin's lymphoma (cHL) is a highly curable lymphoid malignancy. Most of the patients receive either bleomycin or brentuximab vedotin (BV) based therapies as a frontline treatment. Treatment alterations are common and can be related to toxicity, patient's preference, and/or clinical evidence of response. The aim of our study is to explore the frequency and characteristics of treatment alterations, especially bleomycin and BV, in frontline therapies used in newly diagnosed cHL. Methods This single center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Patients' charts were reviewed to assess frequency of treatment discontinuation at the time of frontline therapy and underlying reasons for any treatment alterations. The primary aims were to assess the frequency of treatment alterations and its effects on overall survival (OS), and progression-free survival (PFS). Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and lab measurements, and frequency counts and percentages for categorical variables such as race, gender, and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results In the studied period, 644 patients met the inclusion criteria. The median age at diagnosis was 33 years (range:9-85) with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients. Ninety-seven percent of patients had 0-1 Eastern Cooperative Oncology Group (ECOG) performance status. Histological subtype was predominately nodular sclerosis (83%). International prognostic index at the time of diagnosis was ≥4 in 13% of patients. Most of the patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%). Other therapies included brentuximab vedotin (BV)(13%) and checkpoint inhibitors (CPIs) (6%, as a part of clinical trial). Patient's demographics are outlined in Table.1. Treatment alteration, which included either addition or omission of drug/s, occurred in 26% of patients. The most common discontinued drugs were bleomycin (79%), and BV (15%). Of the patients who were started on ABVD based therapy, the frequency of bleomycin discontinuation was 26% (116 of 455 patients). The most common reasons for bleomycin discontinuation were: treatment response as per the RATHL study (49%), pulmonary toxicity (27%) and other treatment-related toxicity (9%). Of the patients who were started on frontline BV based therapy, the frequency of BV discontinuation was 26% (20 of 78 patients). The most common reasons for BV discontinuation were: peripheral neuropathy (65%), skin rash (10%) and other treatment-related toxicity (25%). Patients who discontinued bleomycin due to adverse events (AEs) had a higher chance of primary refractory disease at the end of frontline treatment (19% vs. 15%, p-value: 0.005) while patients who discontinued bleomycin due to treatment response had similar rates of primary refractory disease (13% vs. 15%, p-value: 0.57). The median cycles number of bleomycin based therapy were the same (6 cycles) among all the groups (those who continued bleomycin without AEs or discontinuation, patients who discontinued bleomycin for treatment response and patients who discontinued bleomycin for AEs) . Patients who discontinued BV due to AEs had similar outcome to the patients who continued the treatment without alterations. Conclusions Frontline treatment alterations in cHL are common. Positron emission tomography treatment response based bleomycin discontinuation was not associated with worse PFS or OS. However bleomycin discontinuation secondary to AEs was associated with a statistically significant higher rate of primary refractory disease and subsequent worse PFS and OS. BV discontinuation secondary to AEs didn't result in worse outcomes. Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Iyer:CRISPR:Research Funding;Spectrum:Research Funding;Merck:Research Funding;Afffimed:Research Funding;Rhizen:Research Funding;Seattle Genetics, Inc.:Research Funding;Legend Biotech:Consultancy;Daiichi Sankyo:Consultancy;Trillium:Research Funding;Curio Biosciences:Honoraria;Target Oncology:Honoraria.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Secura Bio:Other: Grant Support;Astra Zeneca:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Pulse Biosciences:Consultancy;Molecular Templates:Research Funding;BioInvent:Research Funding;VelosBio:Research Funding;Beijing Medical Award Foundation:Honoraria;Juno:Consultancy, Research Funding;Oncternal:Consultancy, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;InnoCare:Consultancy;Loxo Oncology:Consultancy, Research Funding;Verastem:Research Funding;Acerta Pharma:Research Funding;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;OncLive:Honoraria;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Nobel Insights:Consultancy;Guidepoint Global:Consultancy;Dava Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Targeted Oncology:Honoraria.Lee:Celgene:Research Funding;Guidepoint Blogal:Consultancy;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau;Oncternal Therapeutics:Research Funding;Seattle Genetics:Research Funding;Takeda:Research Funding.

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Association of Smoking with Advanced Stage and Survival Outcomes in Classic Hodgkin's Lymphoma

Blood ◽

10.1182/blood-2020-136349 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Samer Al Hadidi ◽

Ranjit Nair ◽

Raphael E Steiner ◽

Sairah Ahmed ◽

Paolo Strati ◽

...

Keyword(s):

Research Funding ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Survival Outcomes ◽

P Value ◽

Advanced Stage ◽

Active Smoking ◽

Time To Event ◽

Grant Support ◽

History Of

Introduction The pathogenesis of classic Hodgkin's lymphoma (cHL) is largely unsettled. Previous studies have provided limited support to the possible association between tobacco smoking and outcome in cHL with inadequate evidence of a dose-outcome relationship. Smoking can result in a multitude of preventable malignancies, thus we studied the association between smoking, the initial stage of cHL and survival outcomes. Methods This single-center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Patients' charts were reviewed to assess the history of active smoking, former smoking and the amount of smoking (measured as pack-year). Former smoking was defined as history of smoking prior to the diagnosis of cHL and no active smoking at the time of diagnosis. The primary aims were to assess overall survival (OS), progression-free survival (PFS) and frequency of advanced disease at the time of diagnosis. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, amount of smoking and lab measurements, and frequency counts and percentages for categorical variables such as race, gender, history of current/prior smoking and response were analyzed. Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results Between 2016 and 2020, 644 patients met the inclusion criteria. The median age at diagnosis was 33 years (range: 9-85 years) with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients. Ninety-seven percent of patients had 0-1 Eastern Cooperative Oncology Group (ECOG) performance status. Histological subtype was predominately nodular sclerosis (83%). International Prognostic Index was =>4 in 13% of patients. Most of the patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%)and checkpoint inhibitors (CPIs) based therapy (6%). Patient's demographics are outlined in Table.1. The percentage of active smoking was low at 6% (median age of active smokers: 33.5). History of prior smoking occurred in 21% of patients. The mean amount of smoking was 1.87 pack-year (rang :0. 05-54 pack-year). Active smoking was associated with advanced stage (9.5% vs. 4.9%, p-value: 0.033). PFS rate at 5 years was similar in smokers and non smokers (52% vs. 54%, p-value 0.9). OS rate at 10 years was better in never smokers when compared to former smokers (95% vs. 77%, p-value: 0.017). Univariable Cox proportional hazards model for OS showed a significant association between amount of smoking and OS with hazard ratio of 1.04 (95% CI: 1.005 1.07, p-value: 0.025). Conclusions We report the largest analysis of smoking status and impact on advanced stage and cHL clinical outcomes. Smoking history is associated with inferior 10 year OS (18% lower OS in patients with history of former smoking). Active smoking was associated with advanced stage however the frequency of active smoking in our patient database was low at 6% compared to previous reports of higher incidence of up to 20%. Patients should be counseled against smoking to avoid worse outcome associated with smoking in many clinical conditions including cHL. Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Iyer:Legend Biotech:Consultancy;CRISPR:Research Funding;Rhizen:Research Funding;Curio Biosciences:Honoraria;Target Oncology:Honoraria;Afffimed:Research Funding;Merck:Research Funding;Spectrum:Research Funding;Trillium:Research Funding;Daiichi Sankyo:Consultancy;Seattle Genetics, Inc.:Research Funding.Nieto:Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support;Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Guidepoint Global:Consultancy;Dava Oncology:Honoraria;Loxo Oncology:Consultancy, Research Funding;Verastem:Research Funding;Beijing Medical Award Foundation:Honoraria;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;OncLive:Honoraria;Molecular Templates:Research Funding;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;MoreHealth:Consultancy;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;BioInvent:Research Funding;Lu Daopei Medical Group:Honoraria;Juno:Consultancy, Research Funding;VelosBio:Research Funding;Acerta Pharma:Research Funding;InnoCare:Consultancy;Oncternal:Consultancy, Research Funding;Nobel Insights:Consultancy.Lee:Celgene:Research Funding;Seattle Genetics:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau;Guidepoint Blogal:Consultancy;Takeda:Research Funding;Oncternal Therapeutics:Research Funding.

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Association of Vitamin D Deficiency with Inferior Treatment Outcomes in Patients with Newly Diagnosed Classic Hodgkin Lymphoma: MD Anderson Cancer Center Experience

Blood ◽

10.1182/blood-2020-142139 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 27-28

Author(s):

Ranjit Nair ◽

Samer Al Hadidi ◽

Raphael Eric Steiner ◽

Sairah Ahmed ◽

Paolo Strati ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Research Funding ◽

Vitamin D Supplementation ◽

Cancer Center ◽

Newly Diagnosed ◽

Time To Event ◽

Grant Support ◽

Vitamin D Levels ◽

Cholecalciferol Supplementation

Introduction Vitamin D deficiency is a modifiable risk factor for multiple malignancies. There is growing evidence that associates vitamin D deficiency with progression-free survival (PFS) and overall survival (OS) in patients with classic Hodgkin lymphoma (cHL). Supplemental ergocalciferol/cholecalciferol may improve chemosensitivity of malignant cells to chemotherapy as evidenced by reduction in the rate of tumor growth in a cHL- xenograft animal model. The goal of our study is to explore the association of pretreatment vitamin D levels on survival outcomes of patients with cHL. Methods We retrospectively reviewed the records of patients who were first seen at The University of Texas MD Anderson Cancer Center between January, 2016 and May, 2020 for newly diagnosed cHL. Patient charts were reviewed to assess demographic information, clinical staging at the time of vitamin D assessment, pretreatment 25-hydroxyvitamin D (25(OH) D) level and vitamin D supplementation. Vitamin D deficiency was defined as a 25(OH)D level < 30 nmol/L. PFS and OS outcomes were evaluated for these patients. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and 25(OH) D level, and frequency counts and percentages for categorical variables such as race, gender, vitamin D supplementation and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results 644 patients met the inclusion criteria of which 483 patients had their vitamin D levels assessed at the time of initial visit to this center. The median patient age at diagnosis was 33 years with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients of which the International Prognostic Score was ≥4 in 13% of patients. Patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%) and other agentss (6%). Patient demographics are outlined in Table.1. Pretreatment 25(OH)D level was assessed in 75% of the patients. The median 25(OH)D level was 25 nmol/L (range: 2-78 nmol/L). Vitamin D deficiency was present in 320 of 483 (66%) patients. Ergocalciferol/cholecalciferol supplementation was used in 29% of patients. There was no statistically significant association of vitamin D deficiency with advanced stage (p-value: 0.64). PFS rate at 10 years was significantly longer in patients with normal 25(OH)D level (40% vs 27%, p-value: 0.0481). Ergocalciferol/cholecalciferol supplementation was associated with a 6% improvement of PFS, however this difference was not statistically significant. No OS difference was noted between vitamin D deficient and non-deficient patients, an observation that persisted in patients on vitamin D supplementation versus not on supplementation. Conclusions Vitamin D deficiency was associated with inferior PFS with a 13% difference in vitamin D deficient versus non-deficient patients. There was a numerical PFS benefit associated with ergocalciferol/cholecalciferol supplementation. An OS benefit was not observed as the duration of follow up may not have been sufficient to observe the differential impact of vitamin D levels. Vitamin D screening and replacement is done in patients with newly diagnosed cHL and should be encouraged given the potential benefit from such approach. Prospective studies are warranted to establish the relationship between vitamin D level, supplementation and outcomes in cHL patients. Figure Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Beijing Medical Award Foundation:Honoraria;OncLive:Honoraria;Molecular Templates:Research Funding;Verastem:Research Funding;Dava Oncology:Honoraria;Guidepoint Global:Consultancy;Nobel Insights:Consultancy;Oncternal:Consultancy, Research Funding;InnoCare:Consultancy;Acerta Pharma:Research Funding;VelosBio:Research Funding;BioInvent:Research Funding;Juno:Consultancy, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;Loxo Oncology:Consultancy, Research Funding;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding.Lee:Takeda:Research Funding;Seattle Genetics:Research Funding;Oncternal Therapeutics:Research Funding;Guidepoint Blogal:Consultancy;Celgene:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau.

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Association of Epstein-Barr Virus with Advanced Stage and Survival Outcomes in Classic Hodgkin's Lymphoma

Blood ◽

10.1182/blood-2020-136338 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-38

Author(s):

Samer Al Hadidi ◽

Ranjit Nair ◽

Raphael E Steiner ◽

Sairah Ahmed ◽

Paolo Strati ◽

...

Keyword(s):

Research Funding ◽

Epstein Barr Virus ◽

Initial Diagnosis ◽

Survival Outcomes ◽

P Value ◽

Time To Event ◽

Barr Virus ◽

Grant Support ◽

Epstein Barr

Introduction Classic Hodgkin's lymphoma (cHL) is a highly curable lymphoid malignancy. Epstein-Barr virus (EBV) is associated with cHL, with a variable rate of detection in Hodgkin and Reed-Sternberg (HRS) cells among different histologic types and geographic areas.Although most adults worldwide are EBV seropositive, only a minority of patients infected with EBV will develop cHL. EBV is thought to be one of the causative agents for the development of cHL with an important pathobiology role. The goal of this study was to compare the presentation and the outcomes of patients with EBV+ HRS cells at the time of initial diagnosis of cHL. Methods This single-center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Pathology was confirmed and analyzed for positivity of EBV (EBV +ve) in all patients by immunohistochemical (IHC) staining for by Epstein-Barr virus-encoded small RNA (EBER) with available paraffin blocks. The primary aims were to assess overall survival (OS), progression-free survival (PFS) and frequency of advanced disease. Descriptive statistics for categorical and continues variables were analyzed. Kaplan-Meier method was used for time-to-event analysis, including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results Between 2016 and 2020, 644 patients met the inclusion criteria. Three hundred and fifty six patients (55%) had enough/available tissue to undergo testing for EBV at the time of initial diagnosis. The median age at diagnosis was 36 years with 51.4% males. Eighty-eight patients had positive EBV (25%) at diagnosis. The median age of +ve EBV was 37 years (Range: 18-83 years) compared to 33 years (Range: 18-85 years) for patients with -ve EBV. Mixed cellularity histology was more frequent in patients with +ve EBV when compared to the whole group of patients (32% vs. 7%; p-value: 0.03). Human immunodeficiency virus (HIV) was positive in a minority of the patients (8 patients out of 498 patients with available results) (1.6%) however 50% of the patients with HIV had +ve EBV at the time of diagnosis. Baseline demographics are summarized in Table 1. EBV was associated with the initial stage (stage II 38% in EBV +ve vs. 53% in EBV -ve, stage III 25% in EBV +ve vs. 14% in EBV -ve, stage IV 24% in EBV +ve vs. 31% in EBV -ve; p-value 0.0001). Most of the patients were treated with doxorubicin, bleomycin, vinblastine and decarbazine (ABVD) based therapy (77%). Other therapies included brentuximab vedotin (BV) (13%) and checkpoint inhibitors (CPIs) (6%). Median follow up was 1.97 years (range: 0.047- 44.09 years). PFS rate difference at 5 years was not statistically significant (64% in EBV +ve vs. 52% in EBV -ve; p-value 0.14). OS rate at 5 years was significantly lower in patients with +ve EBV (89% vs. 98%, p-value: 0.0014). OS rates at 10 years were similar (89% in EBV +ve vs. 88% in EBV -ve). Conclusions EBV at the time of diagnosis was associated with lower prevalence of localized cHL and inferior survival rates at 5 years of follow up (9% lower OS rate at 5 years). Implementation of different frontline therapy treatment algorithms specific to EBV +ve patients may help in improving the survival outcomes. Further research is needed to understand the biological significance of +ve EBV in cHL to help in developing novel agents targeting EBV positive cHL population with the ultimate goal of improving outcome. Disclosures Parmar: Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Iyer:Rhizen: Research Funding; CRISPR: Research Funding; Seattle Genetics, Inc.: Research Funding; Merck: Research Funding; Legend Biotech: Consultancy; Daiichi Sankyo: Consultancy; Trillium: Research Funding; Curio Biosciences: Honoraria; Target Oncology: Honoraria; Afffimed: Research Funding; Spectrum: Research Funding. Nieto:Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Secura Bio: Other: Grant Support. Chuang:Sage-Evidence=Based Medicine & Practice: Consultancy. Wang:Beijing Medical Award Foundation: Honoraria; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Nobel Insights: Consultancy; Verastem: Research Funding; Dava Oncology: Honoraria; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Molecular Templates: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Targeted Oncology: Honoraria; Lu Daopei Medical Group: Honoraria; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Juno: Consultancy, Research Funding; OncLive: Honoraria; Guidepoint Global: Consultancy. Lee:Celgene: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau; Seattle Genetics: Research Funding; Oncternal Therapeutics: Research Funding; Guidepoint Blogal: Consultancy.

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Clinical Characteristics and Outcomes of AML Patients Treated with Frontline CPX 351 or HMA/Venetoclax: A Single Institution's Experience

Blood ◽

10.1182/blood-2021-149811 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1252-1252

Author(s):

Aleksander L. Chojecki ◽

Justin Arnall ◽

Danielle Boselli ◽

Kristyn Y. DiSogra ◽

Allison Karabinos ◽

...

Keyword(s):

Research Funding ◽

Clinical Characteristics ◽

Treatment Options ◽

Standard Of Care ◽

Response Rates ◽

Similar Response ◽

Refractory Disease ◽

Newly Diagnosed ◽

Frontline Treatment ◽

To Receive

Abstract Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P<0.001); many pts in both treatment groups had unfavorable ELN risk scores at diagnosis (CPX 43%, HMA/Ven 41%; P>0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P<0.001). No differences were detected in achievement of MRD negativity by flow cytometry (P=0.51) or molecular profile (P=0.52). Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy.

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Results of the Phase 1b Dose Escalation Study of OPB-111077, Decitabine, and Venetoclax for the Treatment of Newly Diagnosed or Relapsed/Refractory AML

Blood ◽

10.1182/blood-2020-140729 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 10-10

Author(s):

Lindsay Wilde ◽

Ubaldo Martinez-Outschoorn ◽

Neil Palmisiano ◽

Gina Keiffer ◽

Margaret Kasner

Keyword(s):

Dose Escalation ◽

Research Funding ◽

Acid Metabolism ◽

Pharmaceutical Research ◽

Refractory Disease ◽

Newly Diagnosed ◽

Dose Escalation Study ◽

Phase Ib ◽

Otsuka Pharmaceutical ◽

Refractory Aml

Background: The combination of a hypomethylating agent (HMA) and the Bcl-2 inhibitor venetoclax (VEN) has revolutionized the treatment of elderly patients with newly diagnosed acute myeloid leukemia (AML). However, patients treated with this regimen inevitably relapse and subsequent treatment options are limited. Furthermore, the success of this combination in the relapsed/refractory setting has been less impressive. Mechanisms of resistance to HMA/VEN are of great interest, and alterations in leukemic cell metabolism have been implicated. It is hypothesized that drugs that target oxidative phosphorylation (OXPHOS), fatty acid metabolism, and /or amino acid metabolism may be successful in overcoming HMA/VEN resistance. OPB-111077 is a novel, oral, low-molecular-weight compound that was shown in preclinical models to inhibit mitochondrial electron transport and have an inhibitory effect on the growth of AML cells. When given in combination with decitabine, OPB-111077 showed a more potent antitumor effect in a KG-1 tumor-bearing mouse model, thus providing support for conducting clinical trials of this combination. AML cells treated with OPB-111077 and venetoclax have also been shown to have decreased proliferation and increased apoptosis. The effects on proliferation and apoptosis of the combination of OPB-111077 and venetoclax were more pronounced in AML cells that were genetically engineered to increase OXPHOS. These data formed the basis for the development of a clinical trial utilizing the triplet of OPB-111077, decitabine, and venetoclax for the treatment of newly diagnosed or relapsed/refractory AML. Herein, we report results from the Phase Ib dose escalation study. Methods: In this phase Ib single center study (NCT03063944), OPB-111077 is administered daily starting on day 1 and continuing throughout the treatment cycle. Decitabine 20mg/m2 is given for 5 days starting on day 4 of cycle 1. Venetoclax 70mg daily (if receiving posaconazole prophylaxis) or 100mg daily (if receiving voriconazole) is started on day 4 and given continuously until day 28. If a response is seen within 2 cycles, treatment continues until toxicity, disease progression, or availability of an alternative therapy. Patients were enrolled in cohorts of escalating dose levels of OPB-111077 using a traditional 3+3 design. The primary objectives were to determine preliminary safety and tolerability as well as maximum tolerated dose (MTD) of OPB-111077. The secondary objective was to measure preliminary efficacy. Correlative studies including metabolomics, ATP measurement, apoptosis, and proliferative assays were performed on samples of blasts and non-cancerous cells that were collected from blood or marrow. Results: As of July 15, 2020, 2 patients with newly diagnosed AML and 7 patients with relapsed/refractory AML were treated with the triplet. Patients received OPB-111077 at 150mg (n=3), 200mg (n=3), and 250mg (n=3). Median age was 73 years (range, 23-79) and 7 patients (78%) were male. The median number of prior systemic anticancer regimens for patients with relapsed/refractory disease was 2 (range, 1-5); no patients had undergone prior stem cell transplant. The median treatment duration has not yet been reached; 3 patients are receiving ongoing treatment. No patients experienced a dose limiting toxicity. The most common Grade ≥3 adverse event (AE) was febrile neutropenia (56%). No patients discontinued due to AEs. No pts experienced tumor lysis syndrome. Three patients died after completing their study treatment, all due to progressive AML. The best overall response to therapy was a complete remission in 2 (22%) patients (1 with newly diagnosed AML and 1 with relapsed/refractory disease). Metabolomics using liquid chromatography/mass spectrometry was performed on paired pre- and post-treatment samples and intracellular metabolic changes in glycolysis and the tricarboxylic acid (TCA) cycle were observed consistent with on-target effects. Conclusion: The triplet of OPB-111077, decitabine, and venetoclax for the treatment of newly diagnosed or relapsed/refractory AML was safe and well tolerated, and showed preliminary anti-leukemic efficacy. A planned expansion phase is underway utilizing the 250mg daily dose of OPB-111077. Disclosures Martinez-Outschoorn: Otsuka Pharmaceutical: Research Funding. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Kasner:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka Pharmaceutical: Research Funding.

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Pegaspargase Can Safely be Administered in Adults Age 40 and Older with Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood-2019-124727 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3816-3816 ◽

Cited By ~ 2

Author(s):

Ryan J. Daley ◽

Sridevi Rajeeve ◽

Charlene C. Kabel ◽

Jeremy J. Pappacena ◽

Sarah E. Stump ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Board Of Directors ◽

Research Funding ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Hypersensitivity Reactions ◽

Newly Diagnosed ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Frontline Treatment

Introduction: Asparaginase (ASP) has demonstrated a survival benefit in pediatric patients (pts) with acute lymphoblastic leukemia (ALL) and is now part of standard-of-care frontline treatment. As a result, asparaginase preparations have been incorporated into the treatment of adult ALL to improve outcomes. Pegaspargase (PEG-ASP), a modified version of asparaginase with prolonged asparagine depletion, appears to be safe in adults up to age 40 (Stock, et al., Blood, 2019), but is associated with a unique spectrum of toxicities, the risks of which appear to increase with age. Therefore, the safety of PEG-ASP remains a significant concern in older adults w/ ALL. Methods: We conducted a single center retrospective chart review of pts age ≥40 years who received PEG-ASP as part of frontline induction/consolidation or reinduction, between March 2008 and June 2018 at Memorial Sloan Kettering Cancer Center. The primary objective was to evaluate the tolerability and toxicity of PEG-ASP based on the incidence and severity of ASP-related toxicities (hypersensitivity reactions, hypertriglyceridemia, hyperbilirubinemia, transaminitis, pancreatitis, hypofibrinogenemia, etc) according to the Common Terminology Criteria for Adverse Events, version 4.03. Laboratory values recorded were either the peak or the nadir, the more appropriate for toxicity assessment, within a 4-week period following PEG-ASP administration. Secondary objectives were to determine the total number of doses of PEG-ASP administered in comparison to the number of doses intended, and to characterize the rationale for PEG-ASP discontinuation when applicable. Fisher's exact test was used to compare the incidence of PEG-ASP toxicities with respect to pt and treatment characteristics (regimen, age, BMI, gender, Philadelphia chromosome positive (Ph+) vs. Ph-, presence of extramedullary disease, PEG-ASP dose). P values were not adjusted for multiple comparisons. Results: We identified 60 pts with ALL (40 B-ALL and 20 T-ALL) who received at least one dose of PEG-ASP. Nine pts were Ph+. The median pt age at initiation of the treatment was 53, (range, 40 to 80), and 19 pts had a BMI ≥30 kg/m2. Forty-four pts received treatment for newly diagnosed ALL, and 16 pts for relapsed disease. Table 1 lists pt baseline characteristics. Among the 44 pts with newly diagnosed ALL, 27 pts received PEG-ASP as part of pediatric or pediatric-inspired regimens at doses of 2000 - 2500 units/m2, and 1 pt received a modified dose of 1000 units/m2 due to age. The remaining 16 pts received PEG-ASP at doses of 1000 - 2000 units/m2 for consolidation, per established adult regimens (ALL-2 and L-20; Lamanna, et al., Cancer, 2013). Grade 3/4 ASP-related toxicities with a >10% incidence included: hyperbilirubinemia, transaminitis, hypoalbuminemia, hyperglycemia, hypofibrinogenemia, and hypertriglyceridemia. Frontline treatment regimens in which PEG-ASP was used in consolidation cycles only (ALL-2, L-20) were associated w/ a lower incidence of hyperbilirubinemia (p=0.009) and hypertriglyceridemia (p<0.001) compared to those regimens that included PEG-ASP during induction (pediatric/pediatric-inspired regimens) (Table 2). Younger age (40-59 vs. ≥60 years) was associated with a greater risk of hypertriglyceridemia (p<0.001) and higher PEG-ASP dose (≥2000 vs. <2000 units/m2) was associated with a greater risk of hypertriglyceridemia and hypofibrinogenemia (p=0.002 and p=0.025, respectively). Thirty-eight pts (63%) received all intended doses of PEG-ASP. Six pts stopped PEG-ASP to proceed to allogeneic hematopoietic stem cell transplantation (5 in CR1, 1 in CR2), and 7 pts stopped for hypersensitivity reactions. Hepatotoxicity was the only ASP-related toxicity that led to PEG-ASP discontinuation occurring in 5 pts (hyperbilirubinemia, N=4; transaminitis, N=1). The total number of intended doses of PEG-ASP based on regimens used was 186, and 112 were administered. Conclusion: PEG-ASP was incorporated into the treatment of 60 adult ALL pts age ≥40, with manageable toxicity. Seven pts discontinued PEG-ASP due to hypersensitivity reactions and 5 discontinued due to hepatotoxicity, but other reported toxicities did not lead to PEG-ASP discontinuation and the majority of the pts completed all intended doses of PEG-ASP. This study suggests that with careful monitoring, PEG-ASP can safely be administered in adults ≥40 years of age. Disclosures Rajeeve: ASH-HONORS Grant: Research Funding. Tallman:UpToDate: Patents & Royalties; Oncolyze: Consultancy, Membership on an entity's Board of Directors or advisory committees; Delta Fly Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellerant: Research Funding; Tetraphase: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nohla: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioLineRx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; Biosight: Research Funding; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; KAHR: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees. Geyer:Dava Oncology: Honoraria; Amgen: Research Funding. Park:Takeda: Consultancy; Allogene: Consultancy; Amgen: Consultancy; AstraZeneca: Consultancy; Autolus: Consultancy; GSK: Consultancy; Incyte: Consultancy; Kite Pharma: Consultancy; Novartis: Consultancy.

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Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes

Blood ◽

10.1182/blood.v124.21.292.292 ◽

2014 ◽

Vol 124 (21) ◽

pp. 292-292 ◽

Cited By ~ 11

Author(s):

Joseph M Connors ◽

Stephen Ansell ◽

Steven I. Park ◽

Michelle A. Fanale ◽

Anas Younes

Keyword(s):

Hodgkin Lymphoma ◽

Research Funding ◽

Response Rate ◽

Phase 1 ◽

Brentuximab Vedotin ◽

Advanced Stage ◽

Newly Diagnosed ◽

Genetics Research

Background: The ABVD regimen containing doxorubicin, bleomycin, vinblastine, and dacarbazine is a common standard of care for the frontline treatment of advanced stage Hodgkin lymphoma (Santoro 1987; Duggan 2003) and is curative for the majority of patients; however, up to 30% of patients require a secondary therapy. Hodgkin Reed-Sternberg cells of classical HL (cHL) typically express CD30. In a pivotal phase 2 trial brentuximab vedotin (A, ADCETRIS®), comprised of an anti-CD30 monoclonal antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE) induced an objective response rate (ORR) of 75% and complete response rate (CR) of 34% in highly treatment-refractory patients with cHL (Younes 2012). Methods: We conducted a phase 1, open-label, multicenter study to evaluate the safety and efficacy of A when administered in combination with standard therapy (ABVD) or the same regimen without bleomycin (AVD) (Younes 2013). Adult patients with newly diagnosed advanced stage (II bulky, II B, III or IV; 80% stage III or IV) received doses of 0.6, 0.9, or 1.2 mg/kg A with standard doses of ABVD or 1.2 mg/kg with AVD, depending on cohort assignment on Days 1 and 15 of each 28-day cycle for up to 6 cycles of therapy. Previously we reported that among patients assessable for response 95% of patients given ABVD+A achieved a CR, as did 96% of patients given AVD+A. None of 26 patients given AVD+A but 11 of 25 (44%) given ABVD+A experienced pulmonary toxicity, including 2 deaths, establishing that A cannot be safely combined with bleomycin. In this current study we provide the long term survival and safety data on patients enrolled in the phase 1 trial. Results: In total 51 patients were assigned to either ABVD+A (n=25) or AVD+A (n=26). 1 patient who withdrew from the trial during the first cycle of ABVD+A is excluded from this analysis and 1 patient who received 3 cycles of ABVD+A, then withdrew, then received 3 cycles of ABVD alone and 2 patients who died during treatment (pulmonary toxicity) are included (total n=50). Median follow-up from diagnosis for the 24 patients treated with ABVD+A is 41 months (range 9-51 months) and for the 26 patients treated with AVD+A, 31 months (range 9-35 months). All 26 patients treated with AVD+A have been followed longer than the longest time to relapse (7 months). 45 patients remain in first CR and 5 treatment failures have occurred: 4 in the ABVD+A cohort (2 toxic deaths; 2 relapses (9 and 23 months from diagnosis)) and 1 after AVD+A (7 months from diagnosis). 3y-failure-free survival (3y-FFS) is 83% and 96% for ABVD+A and AVD+A, respectively, and 3y-overall survival (3y-OS), is 92% and 100%. No additional toxic deaths have occurred in follow-up. Conclusions: These updated outcomes reflecting the impact of adding brentuximab vedotin (1.2 mg/kg) to standard doses of AVD for classical Hodgkin lymphoma, demonstrating 96% 3y-FFS and 100% 3y-OS with no major unexpected toxicity, strongly support the current large international trial comparing AVD-A (AVD+1.2mg/kg brentuximab vedotin) to standard ABVD (ECHELON-1, clinicaltrials.gov NCT01712490), which may identify a new, less toxic gold standard treatment for advanced stage classical Hodgkin lymphoma. Disclosures Connors: Seattle Genetics: Research Funding. Off Label Use: brentuximab vedotin in phase 1 trial. Ansell:Seattle Genetics: Research Funding. Park:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding. Fanale:Seattle Genetics: Research Funding. Younes:Seattle Genetics: Research Funding; Millennium/Takeda: Research Funding.

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Average Time to Treatment in Lymphoma Patients Undergoing Ovarian Preservation: Experience from a Single Institution

Blood ◽

10.1182/blood.v126.23.2111.2111 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2111-2111

Author(s):

Pamela Blair Allen ◽

Mary Ellen Pavone ◽

Kristin M Smith ◽

Ralph Kazer ◽

Alfred W Rademaker ◽

...

Keyword(s):

Survival Rate ◽

Fertility Preservation ◽

Advanced Disease ◽

Control Group ◽

P Value ◽

Refractory Disease ◽

Newly Diagnosed ◽

Relapse Free Survival ◽

Free Survival ◽

New Diagnosis

Abstract Background: Cryopreservation of oocytes or fertilized embryos prior to initiation of chemotherapy offers women with cancer an opportunity for future pregnancy if fertility is compromised by treatment. To investigate the actual delay in starting chemotherapy associated with fertility preservation protocols in young women with lymphoma, we performed a retrospective chart review of the Northwestern Medicine (NM) institutional experience. Methods: Subjects were identified from a log of women who contacted the fertility preservation patient care navigator (FPPCN) from May 2007 through December 2014. NM practitioners are required to address fertility in all newly diagnosed cancer patients, through the use of automated prompts. Patients were included in the analysis if they had newly diagnosed or relapsed/refractory lymphoma and were treated at NM, whether or not they attempted fertility preservation. The primary endpoint was time to treatment (TTT) initiation. In newly diagnosed patients, TTT was defined as time from NM hematology/oncology consult until the initiation of chemotherapy. In patients with relapsed disease, TTT was measured from time of biopsy at NM or time of consult if biopsy was performed at an outside institution. We used a one-tailed T test to compare independent means with a significance level of 0.05. Results: 128 lymphoma patients contacted the FPPCN between 5/2007- 12/2014 and data on 28 of 36 women who proceeded with fertility preservation (FP) is available for analysis. 50 of 93 lymphoma patients who contacted the FPPCN but did not undergo ovarian stimulation served as a comparison group. The average length of follow up was 152 weeks (range: 14-388 weeks). Reasons patients were excluded from the analysis included lack of chemotherapy treatment records and no treatment received at NM. Among patients undergoing FP, 21 presented with a new diagnosis and 7 with relapsed/refractory disease. The average age was 26 years (range: 20-31). All had ECOG PS of 0/1. Histologies were: 17 HL, 8 DLBCL, and 3 other subtypes. 25 patients had stage I/II and 3 had stage III/IV disease. 4 HL patients had early favorable disease, 12 early unfavorable, and one had advanced disease. Among 50 control patients, 37 presented with a new diagnosis and 13 with relapsed or refractory disease. The average age was 29 years (range 19-45). Histologies included 29 HL, 10 with DLBCL, 11 with other histologies. 31 patients were stage I/II and 15 were stage III/IV 15. 3 HL patients had early favorable disease, 19 had early unfavorable, and 6 had advanced disease with IPS scores ranging from 0-4. Among 28 FP patients, median TTT was 28 days (range: 8-76) versus 15.5 days (range: 0-74) in controls (p-value <0.001). Among relapsed patients, the median TTT was 28 days (range 15-76) for FP patients versus 17 days (range: 0-55) for the control group (p-value = 0.04). 7 patients underwent random start protocol ovarian hyper-stimulation and 21 underwent cycle specific stimulation. The median TTT was 28 days among cycle specific (range 8-76) and 27 days (range 18-39) in random start protocols (p-value = 0.35). Eight of 28 patients in the fertility preservation group had progression/relapse of disease with a one year relapse free survival rate (RFS1) of 78%. Six of 50 patients in the control group progressed with an RFS1 of 94%. There was no difference between rates of progression (p-vale 0.07) between preserved and non-preserved patients. Discussion: Fertility preservation delayed treatment by a median of 13 days compared to controls. There was no difference in treatment delay among patients using the random start versus cycle specific protocols. However, all patients on the random start protocol were off oral contraceptives (OCP's) whereas almost all cycle specific patients were on OCP's, thus allowing them optimal timing of their cycle and reduced time to retrieval. The relapse free survival rate was lower among FP patients compared to controls (78% versus 94% respectively), however this did not meet statistical significance. Patients undergoing FP represent a selected group of patients with high risk disease, and baseline characteristics independent of FP may place them at increased risk of relapse. Whether or not the nearly two week delay required for fertility preservation results in adverse patient outcomes will require further investigation utilizing matched controls. Disclosures Gordon: Dr Leo I. Gordon: Patents & Royalties: Patent for gold nanoparticles pending; Northwestern University: Employment.

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Persistence with Dabigatran Therapy for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation: The Gloria-AF Registry

Blood ◽

10.1182/blood.v128.22.2616.2616 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2616-2616 ◽

Cited By ~ 8

Author(s):

Christine Teutsch ◽

Menno V Huisman ◽

Gregory Y.H. Lip ◽

Hans-Christoph Diener ◽

Sergio J Dubner ◽

...

Keyword(s):

Atrial Fibrillation ◽

Stroke Prevention ◽

Oral Anticoagulant ◽

Research Funding ◽

Stroke Risk ◽

Committee Member ◽

Global Perspective ◽

Newly Diagnosed ◽

Kaplan Meier ◽

Grant Support

Abstract Purpose/Background : Oral anticoagulation is recommended for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) and stroke risk factors, but discontinuation rates are high among those treated with vitamin K antagonists (VKA). After the first year of treatment, about half of patients permanently stop taking VKA therapy. We examined persistence to therapy with dabigatran etexilate (DE) in patients enrolled in the global, prospective GLORIA-AF Registry Program. Methods: GLORIA-AF collects data in three phases from routine clinical practice in 44 countries worldwide. Enrollment in Phase II was initiated following approval of DE, the first non-VKA oral anticoagulant (NOAC) available. During this phase, all patients with newly diagnosed NVAF at risk for stroke starting DE are followed for 2 years. This analysis is based on a pre-specified interim analysis once follow-up of the first 3000 DE patients was completed. Patients were recruited between November 2011 and December 2013 at nearly 1,000 sites worldwide, by cardiologists, neurologists and general practitioners. To reduce selection bias, patients were recruited consecutively, irrespective of antithrombotic therapy. Persistence was defined as time from initiation to discontinuation of therapy for >30 days or substitution of initial treatment by another oral anticoagulant. Persistence rates were analyzed on the basis of a time-to-event analysis using the Kaplan Meier method. Results: Among eligible patients, 2,937 were prescribed DE; 823 (27.4%) in North America, 1,503 (50.1%) in Europe, 194 (6.5%) in Latin America, 54 (1.8%) in Africa/Middle East and 363 (12.1%) in Asia. Overall, 55.3% were male, the median age was 71.0 (range 23-98) years; 36.7% were ≥75 years old. The CHA2DS2VASc score was ≥2 in 88.2%, 78.9% had hypertension, 22.7% diabetes mellitus, 10.1% prior stoke and 24.9% heart failure. All but 5 eligible patients took at least one dose of DE. The probability of remaining on DE treatment was 76.6% at 1 year and 69.2% at 2 years (based on Kaplan-Meier method). At the 2 years visit, half of the permanently discontinued patients (418 out of 828) had switched to another oral anticoagulant. Characteristics of patients discontinuing vs. sustaining therapy and relationships to stroke risk and geographical region will be presented. Conclusions: In this global, prospective, cohort of patients newly diagnosed with NVAF and treated with DE, persistence on therapy was high through 2 years of treatment, with an estimated probability of remaining on treatment of about 77% after 1 year and 70% after 2 years. The detailed results will provide a global perspective on the factors that influence treatment persistence in patients prescribed a NOAC for stroke prophylaxis. Disclosures Teutsch: Boehringer Ingelheim: Employment. Huisman:Boehringer Ingelheim Pharma GmbH & Co.KG: Other: Grant support; GlaxoSmithKline: Other: Grant support; Bayer HealthCare: Other: Grant support; Pfizer: Other: Grant support; Actelion: Other: Grant support. Lip:Bayer, BMS/Pfizer, Boehringer Ingelheim and Sanofi Aventis: Speakers Bureau; Bayer, Astellas, Merck, Sanofi, Bristol-Myers Squibb (BMS)/Pfizer, Daiichi-Sankyo, Biotronik, Portola and Boehringer Ingelheim: Consultancy. Diener:AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novartis, Sanofi Aventis, Syngis and Talecris: Research Funding; Abbott, Allergan, AstraZeneca, Bayer Vital, BMS, Boehringer Ingelheim, CoAxia, Corimmun, Covidien, Daiichi-Sankyo, D-Pharm, Fresenius, GlaxoSmithKline, Janssen-Cilag, Johnson & Johnson, Knoll, Lilly, Medtronic, MindFrame, MSD, Neurobiological Technologies: Honoraria; The Department of Neurology at the University Duisburg-Essen received research grants from the German Research Council (DFG), German Ministry of Education and Research (BMBF), European Union, National Institutes of Health, Bertelsmann Foundation and Heinz: Research Funding. Dubner:steering committee member for Boehringer Ingelheim: Consultancy; St Jude Medical: Research Funding. Changsheng:steering committee member for Boehringer Ingelheim: Consultancy. Rothman:RTI Health Solutions: Employment. Zint:Boehringer Ingelheim: Employment. Elsaesser:Boehringer Ingelheim: Employment. Paquette:Boehringer Ingelheim: Employment. Bartels:Boehringer Ingelheim: Employment. Halperin:Bayer HealthCare: Consultancy; Boehringer Ingelheim: Consultancy.

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Frontline Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin and Prednisone in Patients with Peripheral T-Cell Lymphoma with Less Than 10% CD30 Expression (SGN35-032, Trial in Progress)

Blood ◽

10.1182/blood-2021-151645 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1401-1401

Author(s):

Deepa Jagadeesh ◽

Scott Knowles ◽

Steven M. Horwitz

Keyword(s):

T Cell ◽

Research Funding ◽

Response Rate ◽

Cell Lymphoma ◽

Brentuximab Vedotin ◽

T Cell Lymphoma ◽

Efficacy And Safety ◽

Time To Event ◽

Peripheral T Cell Lymphoma ◽

Secondary Endpoints

Abstract Background Brentuximab vedotin (BV) was the first antibody-drug conjugate to be approved in multiple cancer types (Gauzy-Lazo 2020). The combination of a CD30-directed monoclonal antibody, a protease-cleavable linker, and the microtubule-disrupting agent monomethyl auristatin E drives the anticancer activity of BV by inducing CD30-targeted cell cycle arrest and apoptosis as well as the bystander effect on adjacent cells (Sutherland 2006, Hansen 2016, Schönberger 2018). In the ECHELON-2 phase 3 clinical trial, BV, cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed efficacy in patients with peripheral T-cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by immunohistochemistry when compared with patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (Advani 2019). It is hypothesized that A+CHP will demonstrate efficacy in PTCL with <10% CD30 expression because i) clinical responses to BV have occurred in patients with PTCL, cutaneous T-cell lymphoma, or B-cell lymphoma with low (<10%) and undetectable CD30 expression (Jagadeesh 2019) and ii) CD30 expression levels were not predictive of A+CHP responses in non-systemic anaplastic large cell lymphoma (sALCL) (Advani 2019). Study Design and Methods SGN35-032 is a dual-cohort, open-label, multicenter, phase 2 clinical trial (NCT04569032) designed to evaluate the efficacy and safety of A+CHP in patients with non-sALCL PTCL and CD30 expression of <10% on tumor cells. Up to approximately 40 patients will be enrolled in each of the CD30-negative (expression <1%) and the CD30-low (expression ≥1% to <10%) cohorts. Patients will be enrolled based on local results but only patients with CD30 expression <10% per central confirmation will be analyzed for the primary and secondary endpoints. Patients will receive 21-day cycles of A+CHP for 6-8 cycles. Key inclusion criteria include adults with newly diagnosed PTCL, excluding sALCL, per the World Health Organization 2016 classification; CD30 expression <10% by local assessment; and fluorodeoxyglucose-avid disease by positron emission tomography (PET) and measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist. Patients with previous exposure to BV or doxorubicin will not be eligible. The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Secondary endpoints include ORR by BICR using the modified Lugano criteria (Cheson 2014), complete response rate, progression-free survival (PFS), and duration of response per BICR using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007), overall survival, and safety and tolerability. A PET scan is required at baseline, after Cycle 4, and after the completion of study treatment. Follow-up restaging CT scans will be performed over the next 2 years. In both the CD30-negative and the CD30-low cohorts, efficacy and safety endpoints will be summarized using descriptive statistics to describe continuous variables by cohort. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier (KM) methodology and KM plots will be presented. Medians for time-to-event analyses (e.g., median PFS) will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method. Enrollment is planned for 15 US sites and 32 sites across the Czech Republic, France, Italy, and the UK. Disclosures Knowles: Seagen Inc.: Current Employment. Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding.

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