Clinical and Economic Burden Of Peripheral T-Cell Lymphoma In The United States

Abstract Background Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogeneous subtype of non-Hodgkin lymphoma (NHL). PTCL has a poor prognosis due to advanced stage at presentation, and generally poor response to standard chemotherapy. According to recent SEER estimates, PTCL accounts for about 4% of all NHL cases in the United States each year. To date, few studies have assessed the clinical and economic burden of PTCL. Methods MarketScan data for commercially insured and Medicare supplemental patients were used to retrospectively identify unique PTCL patients. Patients were identified by ICD-9-CM diagnosis codes between October 1, 2007 and June 30, 2011. The time of first PTCL diagnosis code served as the index date, and a second PTCL diagnosis date was used for confirmation. All patients were required to have at least 6 months of continuous enrollment before and 12 months of continuous enrollment after their index date. Patients were excluded if aged <18 years, date of birth or gender were missing, or if they had received a stem cell transplant (SCT) prior to PTCL diagnosis. The control group includes patients that may have any other malignant (excluding PTCL) or non-malignant condition and are considered to represent an average insured patient population from the payer perspective. The control group was matched based on age, sex, region, plan type, payer type, and length of enrollment. Mean cost per month was measured and annualized to provide average yearly costs. Healthcare costs included hospitalizations, pharmacy services, office visits, emergency room visits, hospice stays, SCT, and other patient-related costs (lab procedures, radiology procedures, blood transfusions, and other ancillary procedures). Results Of 2820 patients with ≥1 PTCL diagnosis, 1000 patients were identified that met all inclusion criteria (mean age 56 years, 58% male), and were matched to the control group. On an average annual basis, PTCL patients were hospitalized more often (0.9 vs 0.1 hospitalizations), and experienced a longer length of stay (6.4 vs 4 days) compared with matched controls. In addition, PTCL patients had a higher utilization of office visits (16.2 vs 4.1 visits), pharmacy services (34.2 vs 11.6 prescriptions), emergency room visits (0.8 vs 0.2 visits), and hospice care (0.6 vs 0.1 stays). PTCL patients also experienced higher comorbidities (mean Charlson Comorbidity Index of 1.72 vs 0.39, as determined at index date). Overall, PTCL patients incurred much higher average annual costs compared with matched patients ($75,934.08 vs $4660.64; Table), driven mainly by hospitalizations (32.2% of overall costs) and pharmacy services (19.6% of overall costs). Conclusions PTCL is associated with high resource utilization rates and high overall costs. The development of efficacious treatments for PTCL may offer better disease management and may reduce the clinical and economic burden of PTCL. Disclosures: Potashman: Millennium: The Takeda Oncology Company: Employment. Burudpakdee:Millennium: The Takeda Oncology Company: Consulting researcher Other. Wang:Millennium: The Takeda Oncology Company: Consulting researcher Other, Research Funding. Zhu:Millennium: The Takeda Oncology Company: Employment. Carson:Millennium: The Takeda Oncology Company: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Spectrum, Inc.: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin Pharma, Inc.: Research Funding.

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Economic Burden of Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Study Using the SEER-Medicare Database

Blood ◽

10.1182/blood-2020-136768 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 45-45

Author(s):

Ashley Tabah ◽

David Huggar ◽

Krystal Huey ◽

Ronda Copher ◽

Zheng-Yi Zhou ◽

...

Keyword(s):

Board Of Directors ◽

Economic Burden ◽

Research Funding ◽

Index Date ◽

Publicly Traded ◽

Advisory Committees ◽

Analysis Group ◽

Remission Period ◽

Medicare Database

Introduction: Acute myeloid leukemia (AML) poses significant economic burden on the healthcare system, particularly during induction therapy and at disease relapse. The burden associated with ongoing post-remission therapy is less clear. In patients diagnosed with AML enrolled in Medicare who received an induction therapy and achieved disease remission, we assessed the healthcare resource utilization (HCRU) and costs associated with each disease period (induction, early/late post-remission, and post-relapse). Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, comprising Medicare claims (parts A, B, and D from 2007 to 2016) and the US National Cancer Institute's SEER database (cancer diagnoses from 2007 to 2015). Identified patients had a diagnosis of AML in the SEER registry, were ≥ 65 years at the AML diagnosis date, initiated chemotherapy post-AML diagnosis (i.e. induction), and had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code for AML remission following the start of therapy. Patients were excluded if they had another blood malignancy, had received a prior hematopoietic stem cell transplant, or were enrolled in a clinical trial. Induction was defined as any therapy received from the date of first post-diagnosis chemotherapy initiation (index date) to the end of the cycle during which a patient had an ICD-9/10 code for AML remission. The 6 months prior to the index date was defined as the baseline period. Post-remission therapy was divided into an early post-remission period, which included any therapy initiated within the first 60 days (≤ 60 d) after end of induction, and a late post-remission period, which included therapy initiated more than 60 days (> 60 d) after end of induction. If specific treatment information was available, late post-remission therapy was defined by a treatment switch occurring > 60 d after end of induction. Post-remission therapy ended at the earliest of relapse or end of follow-up (i.e., death, end of eligibility, or end of available data [December 31, 2016]). The post-relapse period was from the date of first AML relapse ICD-9/10 code after remission to the end of follow-up. Baseline patient characteristics, as well as HCRU and costs (adjusted to 2019 US dollars) during the baseline, induction, post-remission, and post-relapse periods, were summarized descriptively. HCRU and costs associated with induction and post-remission therapy periods were assessed during days that were part of a treatment cycle. The average per patient per month (PPPM) HCRU and costs were reported. Duration of response (DoR) from the first remission to the earliest of relapse or death was estimated using Kaplan-Meier analysis. Results: A total of 530 patients were identified. The median age at AML diagnosis was 73 years, 53.6% of patients were male, and 80.6% were white. The median time from index date to the end of follow-up was 13.5 months. Most patients received therapy with hypomethylating agents during the AML treatment. A total of 31.9% of patients who achieved remission did not receive post-remission therapy during follow-up; for these patients, mean (median) time from end of induction to relapse or end of follow-up was 125 (23) days. A total of 63.2% of patients received chemotherapy in the early post-remission period, and 43.0% of all patients went on to receive chemotherapy in the late post-remission period. The median DoR was 5.8 months; a total of 48.9% of patients had relapsed and 80.2% had died by the end of follow-up. The mean PPPM healthcare costs were highest for induction, followed by post-relapse, early post-remission, and late post-remission periods (Table). Costs associated with the inpatient (IP) setting were the greatest contributor to PPPM costs across all periods. IP visits were most common during induction with 92.1% of patients having ≥ 1 IP visit, relative to 53.8% during baseline, 65.7% during early post-remission, 71.5% during late post-remission, and 91.1% post-relapse. Conclusions: The economic burden of relapse is approximately 1.2 and 1.6 times higher than the mean PPPM healthcare costs during early and late post-remission periods, respectively. There exists a large unmet need for therapies that will extend the duration of the post-remission period and reduce the overall economic burden of AML. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Huggar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company; FibroGen: Current equity holder in publicly-traded company. Huey:Bristol Myers Squibb: Current Employment. Copher:Bristol Myers Squibb: Current Employment. Zhou:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Zichlin:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Koenigsberg:BMS: Other: Employee of Analysis Group Inc., which received consulting fees. Brunner:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Research Funding; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

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Favorable Long-Term Outcomes after Daratumumab Discontinuation in AL Amyloidosis Patients Achieving Deep Responses

Blood ◽

10.1182/blood-2019-124981 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1884-1884 ◽

Cited By ~ 1

Author(s):

Alfred Chung ◽

Gregory P. Kaufman ◽

Surbhi Sidana ◽

David Iberri ◽

Erik Eckhert ◽

...

Keyword(s):

Disease Progression ◽

Board Of Directors ◽

Median Duration ◽

Research Funding ◽

Control Group ◽

Al Amyloidosis ◽

Cell Transplant ◽

Advisory Committees ◽

Free Interval ◽

Significant Difference

Daratumumab (DARA) is a CD38-targeted antibody FDA-approved for the treatment of multiple myeloma (MM) and its efficacy has recently been demonstrated in the treatment of AL amyloidosis. DARA is conventionally given indefinitely until evidence of disease progression or intolerance for the treatment of MM. In AL amyloidosis, the optimal duration of therapy is not known, and patients may be treated indefinitely on maintenance, extrapolating from MM data. However, the plasma cell burden observed in AL amyloidosis is often lower than in MM, and thus certain patients achieving deep responses may have durable responses with time-limited treatment. Outcomes for patients who are observed after DARA discontinuation are not known. We report the outcomes of patients at our institution who received time-limited DARA. A retrospective analysis of AL amyloidosis patients treated at Stanford University from 2016 to 2019 with DARA monotherapy and dexamethasone for at least 2 months was performed, and patients who subsequently had DARA discontinued for reasons other than disease progression or lack of response were selected for the study. Hematologic responses were assessed by consensus guidelines. Duration on and off therapy were explored, along with time-to-next treatment or death (TTNT), defined as the time from DARA initiation to restarting/switching therapy or death. An exploratory analysis comparing TTNT between the study population and a control cohort who achieved hematologic CR and were maintained on DARA was conducted with the Kaplan-Meier method and log-rank testing. 67 patients received at least 2 months of DARA monotherapy and dexamethasone; among these, 15 patients discontinued therapy for reasons other than disease progression and were included. Median age was 66 years old and median lines of prior therapies was 4 (range: 1 - 6). Baseline difference between involved and uninvolved free light chains (dFLC) prior to DARA initiation was 2.6 mg/dL (range: 0 - 16.8 mg/dL). 10 of 15 patients had cardiac involvement with median NT-proBNP of 1982 pg/mL and 9 of 15 patients had renal involvement with median 24-hour proteinuria of 6.2 g and eGFR of 32 mL/min/1.73m2 at DARA initiation. Median duration from starting to stopping DARA was 7.8 months (range: 2 - 21 months). Median duration from achieving best hematologic response to stopping DARA was 3 months (range: 0 - 17 months). Reasons for discontinuation included: patient preference (5), fatigue/body aches (4), infection (2), other active medical comorbidities (3), and lack of perceived further benefit (1). At DARA discontinuation, median dFLC was 0.1 mg/dL (range: 0 - 2.2 mg/dL) and there were 12 hematologic CR, 1 VGPR, 1 PR, and 1 not assessable for response. Outcomes for all 15 patients are shown in Figure 1. The median treatment-free interval was 17.5 months (range: 5 - 34 months); estimated 2-year TTNT-free survival was 83% (95% CI: 61 - 100%). All 14 evaluable patients eventually achieved CR. 3 patients restarted DARA for rising dFLC, and all 3 patients demonstrated response to retreatment (2 achieving CR and 1 near PR with ongoing follow-up). There were 2 deaths. One patient with severe baseline cardiac amyloidosis developed sudden rise in dFLC after treatment-free interval of 21 months; although he rapidly achieved hematologic CR on retreatment, he died of heart failure within 2 months of restarting DARA. The other patient developed therapy-related AML while off therapy and underwent allogenic stem cell transplant but died of leukemia (censored for AL amyloidosis outcomes at transplant). There was no significant difference in the TTNT between the study group and a control group of 16 patients who achieved CR and were on continuous maintenance (Figure 2; p=0.807). AL amyloidosis patients achieving deep responses with DARA can have favorable outcomes after treatment discontinuation, including a long treatment-free interval. Although our sample size is small, the outcomes of these patients appeared comparable to those achieving CR on continuous DARA maintenance, and patients were able to regain responses when retreatment was necessary. These results suggest that DARA may be safely discontinued in patents achieving deep hematologic responses, which has significant implications for quality of life and financial burden of treatment. Future studies evaluating time-limited versus continuous DARA maintenance after achievement of deep responses are warranted. Disclosures Kaufman: Janssen: Other: travel/lodging, Research Funding. Liedtke:Janssen: 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; Prothena: 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; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celator: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Daratumumab for treatment of AL amyloidosis

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Predictors of Maternal Morbidity Among Participants Enrolled in the Sickle Cell Disease Implementation Consortium Registry

Blood ◽

10.1182/blood-2020-140743 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-3

Author(s):

Rita V Masese ◽

Dominique Bulgin ◽

Liliana Preiss ◽

Mitchell Knisely ◽

Eleanor Stevenson ◽

...

Keyword(s):

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Transfusion Requirement ◽

The United States ◽

Acute Chest Syndrome ◽

Maternal Outcomes ◽

Maternal Complications ◽

Advisory Committees ◽

Increased Risk

Introduction Pregnancy in sickle cell disease (SCD) is associated with an exacerbation of SCD-related complications and an increased risk of maternal complications. The increased risk is partly due to physiologic adaptations in pregnancy, which include increased metabolic demands and a hypercoagulable state. The maternal death rate for SCD is 629 per 100,000 deliveries, compared to 12 per 100,000 deliveries in black women and 6 per 100,000 deliveries in the general population (Raider et al., 2016). Studies on maternal and perinatal outcomes of patients with SCD present inconsistent and conflicting results. Some studies have reported an increase in maternal complications such as pre-eclampsia, acute chest syndrome and thromboembolic events, while other studies have reported no significant risk in adverse maternal outcomes. The inconsistent findings reported in prior studies may be attributed to small sample sizes and single-centered sites. Our study aims to determine the prevalence and predictors of maternal morbidity among participants enrolled in the SCD Implementation Consortium (SCDIC) registry, which is the largest, most geographically diverse SCD participant sample in the United States. Methods This cross-sectional study included women enrolled in the SCDIC registry who had at least one pregnancy event. The SCDIC is composed of eight academic SCD centers across the United States and one data-coordinating center. Participants were enrolled in the SCDIC registry if they were 18 to 45 years of age and had a confirmed diagnosis of SCD. Enrolled participants completed a series of surveys that collected sociodemographic information, SCD and pregnancy history and data abstractions of participants' medical records was completed. Medical complications queried during pregnancy included: vaso-occlusive episodes, acute chest syndrome, blood transfusion requirement, preeclampsia, maternal diabetes and deep venous thrombosis. Descriptive analysis of sociodemographic, clinical and maternal characteristics was conducted. Bivariate analysis was performed using Chi-Square test, Mann-Whitney U test, t-test, and logistic regressions, as appropriate. A p-value of ≤ 0.05 was considered statistically significant for all analysis. Results The study sample included 743 women who had at least one pregnancy event, and a total of 1066 live births. Almost all women (96.3%) were African American, with a median age of 21 years (inter-quartile range of 19 to 23 years) at first birth. The majority had Hb SS SCD genotype (69.5%; 513 of the 738 with SCD genotype data). Of all reported pregnancies, participants did not use hydroxyurea during conception (78%), and pregnancy (84.5%). Only 2.7 % of the women reported using fertility drugs or assisted reproductive procedures. Seventy five percent of the pregnancies that ended in live births had maternal complications. The leading complications were vaso-occlusive episodes (61.2%), pregnancy requiring blood transfusion(s) (33.2%), preeclampsia (15.4%), deep venous thrombosis (5.6%) and acute chest syndrome (7.7%). When the pregnancies were stratified by SCD genotype, women with Hb SS had a higher occurrence of acute chest syndrome (63.4% vs. 26.7%), transfusion requirement (70.8% vs. 21%) and preeclampsia (66.7% vs 22.4%). In the univariate logistic regressions, multiparous women, with a history of adverse maternal outcomes in a previous pregnancy, had higher odds of vaso-occlusive episodes (OR: 3.42; 95% CI: 2.42-4.94) acute chest syndrome (OR:4.99; 95% CI:2.56- 9.48), transfusion requirement (OR:3.86; 95% CI:2.64- 5.69), and pre-eclampsia (OR:3.36; 95% CI:2.05-5.45). Conclusion In this large multicenter registry, we found pregnant women with SCD have significant maternal complications. Early antenatal care by healthcare providers knowledgeable about risk factors for adverse maternal outcomes in SCD is essential improve maternal and fetal outcomes and reduce the maternal death rate for SCD. Disclosures Hankins: Novartis: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; MJH Life Sciences: Consultancy, Patents & Royalties; UptoDate: Consultancy; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria. Treadwell:Global Blood Therapeutics: Consultancy; UpToDate: Honoraria. King:Amphivena Therapeutics: Research Funding; Bioline: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Guidepoint Global: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Sanofi: Consultancy. Glassberg:Pfizer: Research Funding; Global Blood Therapeutics: Consultancy; Eli Lilly and Company: Research Funding. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; CSL Behring: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau.

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Emicizumab-Kxwh for Previously Untreated Patients with Haemophilia: The Conversation Begins

Blood ◽

10.1182/blood-2019-127270 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2409-2409

Author(s):

Tiffany Lin Lucas ◽

Shveta Gupta ◽

Joanna A. Davis ◽

Fernando F. Corrales-Medina

Keyword(s):

Board Of Directors ◽

Real World ◽

Research Funding ◽

Hemophilia A ◽

The United States ◽

Haemophilia A ◽

Advisory Committees ◽

Inhibitor Development ◽

Increased Risk ◽

Prophylaxis Therapy

Introduction: With the Federal Drug and Administration approval of the use of emicizumab from birth to adulthood, clinicians will now grapple with when to choose and offer emicizumab for routine prophylaxis, especially in previously untreated patients (PUPs). Given the overall limited real-world reported data and experience using emicizumab in PUPs, we created and administered a survey to medical providers in the United States who care for paediatric patients with haemophilia to investigate real-world practice strategies and treatment selection for PUPs. Methods: After review and endorsement by the Haemostasis and Thrombosis Research Society (HTRS), the survey was electronically distributed by e-mail to all providers included in the HTRS core member list. The survey was also sent to those providers included in a list of Haemophilia Treatment Centre (HTC) physicians (with duplicate emails reconciled). Providers needed to self-identify as ones that treat pediatric patients to be included. The survey was developed as a tiered survey with questions presented to each recipient based on their prior responses. Results: Seventy-seven completed surveys were included and analysed. All participants were active providers at a comprehensive HTC and the majority (93.4%) were practicing at an academically affiliated site. In terms of characteristics of those that answered the survey, forty-eight percent of responders reported that 1-20% of their patients had expressed interest in emicizumab. 46% of participants (34/74) reported that they would personally consider emicizumab as their prophylaxis recommendation for the majority (>50%) of their hemophilia A patients without inhibitors. 57% (44/76) reported that 1-10% of their non-inhibitor hemophilia A patients were already prescribed emicizumab prophylaxis. Each participant was then asked about his or her consideration of emicizumab as prophylaxis therapy for a 2 month old PUP. Just over the majority were unsure or said no to this consideration (51.3%) and their concerns were lack of information on safety and efficacy in this young age group and increased risk for inhibitor development. If the 2 month old PUP had a high risk of inhibitor, the majority of providers who initially were hesitant to start emicizumab prophylaxis would remain so. Of note, those providers went on to be asked if the patient had gone on to complete 50 exposure days without inhibitor development, they would then become more likely to initiate emicizumab prophylaxis therapy. Use of concurrent factor replacement was posed to all participants and there were varied responses. Discussion: Overall, our results reflect a widespread practice variation and a not yet well-standardized or defined approach for the use of emicizumab in PUPs with haemophilia A. In this survey, patient preference and individual bleeding risk were the top reasons for which a provider would consider using switching to emicizumab prophylaxis in both severe and mild/moderate haemophilia A patients. This pattern of practice reflects the current era of individualized medicine. Overall, our findings reinforce the need for more studies to investigate the outcomes of a combined treatment approach with FVIII concentrates and emicizumab focusing in the potential benefit of this approach in decreasing the risk for inhibitor development PUPs. Clinicians also feel the need for further data to help clarifying the safety of emicizumab in this population. Figure Disclosures Gupta: Novartis: Honoraria, Speakers Bureau; CSL Behring: Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Davis:Sanofi: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Shire: Consultancy; Spark Therapeutics: Consultancy. Corrales-Medina:Kedrion: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees.

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Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE): First Detailed Report of Primary Treatment

Blood ◽

10.1182/blood.v120.21.1614.1614 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1614-1614 ◽

Cited By ~ 5

Author(s):

Francine M. Foss ◽

Kenneth R. Carson ◽

Lauren Pinter-Brown ◽

Steven M. Horwitz ◽

Steven T. Rosen ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Board Of Directors ◽

Initial Treatment ◽

Research Funding ◽

Cell Lymphoma ◽

Primary Treatment ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Advisory Committees

Abstract 1614 Background: Registries can be invaluable for describing patterns of care for a population of patients. COMPLETE is a registry of peripheral T-cell lymphoma (PTCL) patients designed to identify the lymphoma-directed treatments and supportive care measures that PTCL patients receive. We report here the first detailed findings of initial therapy. Methods: This is a prospective, longitudinal, observational registry that is led by a global steering committee. Patients with newly diagnosed PTCL and providing written informed consent are eligible. Patients are entered into the registry from time of initial diagnosis and followed for up to 5 years. Only locked records are reported. Results: As of July 2012, 330 patients have been enrolled from the United States. The first patient was enrolled in February 2010. Locked baseline and treatment records are available for 124 and 81 patients, respectively. Of the 124 patients with locked baseline records, 67 patients (54%) were male, the mean age was 59 (range: 19–89), and race/ethnicity was recorded as: White (87 patients; 70%), Black (19; 15%), Asian (5; 4%) and other/unknown (13; 11%). Histology was reported as follows: PTCL-not otherwise specified (27%), anaplastic large cell lymphoma-primary systemic type (18%), angioimmunoblastic T-cell lymphoma (17%), transformed mycosis fungoides (7%), T/NK-cell lymphoma-nasal and nasal type (6%), adult T-cell leukemia/lymphoma, HTLV 1+ (6%) and other (19%). 25 patients (20%) had received another diagnosis, including B-cell lymphoma, Hodgkin's disease and other T-cell lymphomas, prior to their current diagnosis of PTCL. 49 patients (40%) had B symptoms, 102 patients (82%) had an Ann Arbor stage of III/IV, 116 patients (94%) had ECOG performance status of 0–1, and international prognostic index (IPI) score was distributed as follows: IPI 0 (7% of patients), 1 (15%), 2 (43%), 3 (26%), and 4 (9%). Of the 81 patients with locked treatment records, details on initial treatment can be found in table below. Conclusions: This first detailed analysis of primary treatment of PTCL indicates that this disease is still largely being treated with regimens derived primarily from studies of B-cell lymphomas and that a single standard of care does not exist. The fact that a meaningful proportion of patients were initially diagnosed with something other than their current diagnosis of PTCL points out the challenges of diagnosing the disease. While the intent of initial treatment for most patients is to affect a cure, more than 20% of patients were noted as deceased at the end of initial treatment, underscoring the need for more effective, disease-specific therapy. Disclosures: Foss: Merck: Study Grant, Study Grant Other; Celgene: Study Grant, Study Grant Other; Eisai: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Allos: Consultancy. Carson:Allos: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Pinter-Brown:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos: Consultancy, Research Funding. Rosen:Allos: Consultancy, Honoraria. Pro:Celgene: Honoraria, Research Funding; Spectrum: Honoraria; Allos: Honoraria; Seattle Genetics: Research Funding. Gisselbrecht:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hsi:Allos: Research Funding; Eli Lilly: Research Funding; Abbott: Research Funding; Cellerant Therapeutics: Research Funding; BD Biosciences: Research Funding; Millenium: Research Funding.

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An Update On The Clinical Activity Of Resimmune, a Targeted Therapy Directed To CD3 Receptor, In Patients With Cutaneous T Cell Lymphomas--CTCL

Blood ◽

10.1182/blood.v122.21.4381.4381 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4381-4381 ◽

Cited By ~ 2

Author(s):

Arthur E. Frankel ◽

Jung H Woo ◽

Jeremy P Mauldin ◽

Francine M. Foss ◽

Madeleine Duvic ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Pichia Pastoris ◽

Cell Line ◽

Board Of Directors ◽

Research Funding ◽

Response Rate ◽

The United States ◽

Advisory Committees ◽

Systemic Therapies

Abstract Cutaneous T cell lymphoma—CTCL is a malignancy of skin-tropic T cells. CTCL cells have ubiquitous overexpression of CD3. Although uncommon, CTCL has been estimated to affect 1,500 patients per year in the United States. There are multiple approved systemic therapies for CTCL, but responses are brief lasting months. Allogeneic stem cell transplantation may provide long-term remissions, but is suitable for only rare CTCL patients. Overall, CTCL has a long clinical course with relentless progression over months to years with estimated median survival of 3-5 years for stage IB-IIB patients. The CD3 targeted agent, Resimmune, was synthesized and prepared for clinical use. It consists of the catalytic and translocation domains of diphtheria toxin fused to two anti-human CD3 Fv fragments. DNA encoding Resimmune protein was integrated into the Pichia pastoris genome, and recombinant protein was produced in Pichia pastoris via the secretory route (Woo, Protein Expr Purif 25, 270, 2002). Protein was purified by anion exchange and size exclusion chromatography. The CD3+ Jurkat cell line incubated with Resimmune yielded an IC50 for protein synthesis inhibition of 0.017pM. The CD3- Vero cell line incubated with Resimmune showed an IC50 >10pM. Mice, rats, and monkeys given total doses of >200mg/kg over four days showed only transient transaminasemia without histopathologic tissue injury or clinical signs or symptoms (Woo, Cancer Immunol Immunother 57, 1225, 2008). In a mouse model with human CD3e transfected lymphocytes, four logs of antigen positive cells were reproducibly depleted from nodes and spleen with 100mg/kg total dose of Resimmune (Thompson, Protein Eng 14, 1035, 2001). Based on these findings, a phase 1 study was initiated and this report serves to update the results of a single cycle of Resimmune given at 2.5-11.25mg/kg 15 min IV infusion twice daily for 8 doses to 18 CTCL patients. There were 10 females and 8 males with ages 20-81 years. Two patients were naïve to systemic therapies, and all others had failed 1-4 prior treatments including interferon, bexarotene, gemcitabine, vorinostat, chlorambucil, etoposide, pralatrexate, doxil, romidepsin, methotrexate, CHOP, and brentuximab vedotin. None of the Resimmune treated CTCL patients had dose-limiting toxicities. Side effects were mild-moderate and transient with fevers, chills, nausea, transaminasemia, hypoalbuminemia, lymphopenia, reactivation of EBV and CMV, and hypophosphatemia. Toxicities responded to antipyretics, anti-emetics, albumin infusions, rituximab treatment and valgancyclovir. Among measured patients, there was a 3 log decline in normal, circulating T cells by day 5 that recovered by day 14. Because of vascular leak syndrome toxicities in non-CTCL patients, the MTD was defined as 7.5mg/kg x 8 doses. Cmax ranged from 1.9-40.7ng/mL and half-life from 5-66min. Pretreatment anti-DT titers were 0.9-251mg/mL and day 30 post-therapy increased to 5-4059 mg/mL. 17 CTCL patients were evaluable for response. There were six responses for a response rate of 35%. There were four CRs (24% CR rate). Three of the CRs are over 4-years duration. Patients with IB or IIB disease and mSWAT<50 had an overall response rate of 86% and CR rate of 56%. The long time required to convert from a PR to a CR in the absence of any additional therapy beyond the four treatment days suggest an additional anti-tumor mechanism beyond immunotoxin-induced killing such as immunomodulation. Accrual of patients with mSWAT scores of 50 or less is ongoing. Disclosures: Woo: Angimmune: Patents & Royalties, Research Funding. Foss:celgene: Honoraria, Research Funding; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees; eisai: Membership on an entity’s Board of Directors or advisory committees; spectrum: Research Funding; merck: Research Funding; seattle genetics: Research Funding. Neville:Angimmune: Employment, Equity Ownership, Patents & Royalties.

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Progression-Free Survival and Overall Survival Among a Patient Cohort of Relapsed/Refractory Mycosis Fungoides in France, Germany, Italy, Spain and the United Kingdom

Blood ◽

10.1182/blood-2019-126246 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5879-5879

Author(s):

Martine Bagot ◽

Timothy Illidge ◽

Nicola Pimpinelli ◽

Mehul Dalal ◽

Athanasios Zomas ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Mycosis Fungoides ◽

Systemic Therapy ◽

Research Funding ◽

Index Date ◽

Progression Free Survival ◽

High Rate ◽

Advisory Committees ◽

Free Survival

Background and Aim: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL) wherein those with advanced stage have a poor prognosis. The objective of this study was to describe clinical characteristics and survival in MF patients who were refractory or had relapsed after a first systemic therapy. Methods: A retrospective chart review study was conducted at 27 sites in Europe. Patients enrolled had a diagnosis of MF and proved to be relapsed/refractory (R/R) prior to 1-Jan-2016 after a first systemic therapy. Overall survival (OS) and progression-free survival (PFS) were estimated from the date of R/R event (defined as the index date) using Kaplan-Meier estimates. PFS was defined as death, progression, second relapse or refractory, or presence of subsequent treatment after index date. Results: This study included 104 advanced R/R MF patients with a median age of 54.5 years (range: 21-82). The median follow-up was 3.5 years (range: 0-20.7) after index date. In total 80% of patients experienced a second R/R, with a median time to second R/R of 15.8 months (range: 0.6-174.6). The median age at death was 65 years (range: 42-85). In total 39 deaths (37.5%) were observed. Among those patients who had a known cause of death (N=35), 18 died of CTCL progression, 11 of CTCL complication or drug toxicity and 7 of other causes. The estimated median OS was 11.5 years (95% CI: 6.5 - not reached). The median PFS was 1.3 years (95% CI: 1.0-2.1). Conclusions: The high rate of R/R and low PFS suggest that the clinical burden of R/R MF is significant in five European countries, and recently approved targeted therapies have the potential of improving outcomes. Disclosures Bagot: Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Illidge:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics, Inc.: Research Funding; Div of Cancer Sciences, Faculty of Biology, Medicine and Health, Univ of Manchester, National Institutes of Health and Research Biomedical Research Center, Manchester Academic Health Sciences, Christie Hospital National Health Service Foundation Trust: Employment. Dalal:Takeda: Employment. Zomas:Takeda: Employment. Trinchese:Takeda: Employment. Little:Takeda: Employment. Bent-Ennakhil:Takeda Pharmaceuticals International AG: Employment. Ortiz-Romero:Actelion: Consultancy, Membership on an entity's Board of Directors or advisory committees; 4SC: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; miRagen: Membership on an entity's Board of Directors or advisory committees; PLCG1: Patents & Royalties; Kyowa: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; MEDA: Research Funding.

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Metformin Restores AMPK Alpha-Mediated Autophagy and Prevents Carfilzomib-Induced Cardiotoxicity In Vivo

Blood ◽

10.1182/blood-2018-99-112351 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3214-3214

Author(s):

Georgios Kremastiotis ◽

Panagiotis Efentakis ◽

Aimilia Varela ◽

Constantinos H. Davos ◽

Maria Tsoumani ◽

...

Keyword(s):

Signaling Pathways ◽

Board Of Directors ◽

Molecular Mechanism ◽

Research Funding ◽

Steering Committee ◽

Control Group ◽

Advisory Committees ◽

Pp2a Activity ◽

Travel Grant

Abstract Introduction: Carfilzomib (Cfz) significantly prolongs progression-free survival in relapsed or refractory multiple myeloma patients, as highlighted in the ENDEAVOR trial. However, Cfz has high incidences of cardiotoxicity and heart failure, leading to treatment cessation. Thus, there is an imperative need for preventive therapies. The study aimed to i) establish an in vivo Cfz cardiotoxicity protocol, ii) investigate the molecular mechanism, identify molecular targets and iii) based on initial results, investigate the potential protective effect and mechanism of Metformin (Met). Methods: Male, C57BL/6 mice, were randomized in groups as following: Acute protocol (6 days): Control (n=7), Cfz (n=8); Sub-chronic protocol (14 days): Control (n=5), Cfz (n=8); Pharmacological intervention protocol (6 days): Control (n=8), Cfz (n=8), Cfz+Met (n=8), Met (n=4). Cfz (8 mg/kg, ip) was administered on alternate days and Met (140 mg/kg, po) daily. Glucose levels were monitored following Met administration. Mice underwent echocardiography on baseline and at the end of treatments. Blood and myocardial tissue samples were obtained for histology, proteasome activity, PP2A activity and signaling pathways focused on PI3K/Akt/eNOS axis, NO homeostasis and AMPKα-mTOR-mediated autophagy. Results: Following acute administration, echocardiography in Cfz group presented a significant reduction in fractional shortening (FS%) vs. Control group (39.87±0.47 vs. 43.03±0.50 respectively, p<0.001), combined with reduced thickness in the left ventricular (LV) posterior wall (LVPW diastole (mm): 0.69±0.01 vs. 0.76±0.01, p<0.01; LVPW systole (mm): 1.17±0.01 vs. 1.24±0.02, p<0.01). Sub-chronic Cfz administration resulted in moderate LV dilation (LV end-diastole diameter (mm): 3.24±0.03 vs. 3.04±0.04, p<0.01; LV end-systole diameter (mm): 1.88±0.02 vs. 1.71±0.02, p<0.01) and borderline FS% reduction (42.07±0.46 vs. 43.52±0.25, p<0.05). Following both protocols, Cfz did not cause major tissue lesions. Signaling pathways were studied in the acute protocol that demonstrated suppressed myocardial contractility. Cfz resulted in significant inhibition of proteasome in both myocardium (55.5% inhibition, p<0.05) and peripheral mononuclear blood cells (PBMCs) (90.6% inhibition, p<0.001) - inhibitory effect was comparable to clinical practice. Cfz, independently of PTEN expression, reduced phospho-PI3K (p<0.05), phospho-Akt (p<0.001) and phospho-eNOS (p<0.001), and increased iNOS expression (p<0.01). Cfz reduced phospho-AMPKα (p<0.001) and phospho-Raptor (p<0.05) leading to inhibition of autophagy, indicated by reduced LC3-II expression (p<0.01), without affecting phospho-mTOR or Beclin 1. Co-administration of Met prevented FS% reduction (Cfz group: 41.55±0.43 vs. 43.24±0.50 and 43.39±0.56, Control and Cfz+Met respectively, p<0.05), without exerting glucose lowering actions. Met did not interfere with Cfz-induced proteasome inhibition; Cfz and Cfz+Met groups had significantly reduced proteasomal activity vs. Control group in myocardium (p<0.05) and PBMCs (p<0.001 and p<0.01 respectively). Histology presented mild to moderate vascular congestion in Cfz+Met and Met vs. Control and Cfz groups (p<0.05), appearing to be non-specific finding that did not collocate with haemorrhage, vascular obstruction or tissue lesions. On a molecular level, Cfz+Met group presented increased phospho-Akt (p<0.01) vs. Cfz group, independently of PTEN, PI3K and eNOS/iNOS. Cfz+Met group restored phospho-AMPKα (p<0.05), phospho-Raptor (p<0.001) and LC3-II expression (p<0.05) vs. Cfz group, without inducing changes in mTOR and Beclin 1. Cfz inactivated Akt and AMPKα through increased PP2A activity (p<0.05), without altering PP2A expression; Met did not interfere with PP2A activity. Conclusions: Cfz exhibits decreased global LV function in vivo, without inducing tissue lesions. The molecular mechanism consists of increased PP2A activity leading to inactivation of AMPKα-mTOR and PI3K/Akt/eNOS pathways - combined with NO homeostasis deregulation. In an intervention approach, Met preserved cardiac function via restoring AMPKα-mediated autophagy. Met administration did not restore NO production and homeostasis; these pathways require further investigation. Met emerges to be a promising preventive therapy for Cfz-induced cardiotoxicity. Disclosures Kastritis: Amgen: Consultancy, Honoraria, Research Funding; Genesis Pahrma: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Honoraria; Prothena: Consultancy, Honoraria. Dimopoulos:Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria. Terpos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; BMS: Consultancy; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding.

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Central Nervous System Involvement By Mantle Cell Lymphoma

Blood ◽

10.1182/blood-2021-148447 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2426-2426

Author(s):

Nicole McLaughlin ◽

Jonas Paludo ◽

Yucai Wang ◽

David J. Inwards ◽

Nora Bennani ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Data Monitoring Committee ◽

Advisory Board ◽

Control Group ◽

Cns Involvement ◽

Extranodal Involvement ◽

Advisory Committees ◽

Scientific Advisory Board ◽

Scientific Advisory

Abstract Background: While extranodal involvement by mantle cell lymphoma (MCL) is relatively common, involvement of the central nervous system (CNS) is rare (<5% of cases), with limited treatment options. We report the outcomes of 36 patients (pts) with CNS involvement compared to 72 matched control MCL pts without CNS involvement. Methods: MCL pts with CNS involvement seen at Mayo Clinic between 1/1995-9/2020 were identified using the Mayo Data Explorer tool. CNS involvement was defined by tissue biopsy confirmed CNS MCL, CSF analysis demonstrating lymphoma cells, and/or neuroimaging findings compatible with CNS involvement. A 2:1 control group of MCL pts without CNS involvement, matched by age (+/- 2 years) and year of diagnosis (+/- 1 year), was selected among all MCL cases. Medical records were reviewed for baseline characteristics, treatment modalities, and outcomes. Kaplan-Meier method was used for time to event analysis. Wilcoxon test was used to compare continuous variables and Chi square test was used for categorical variables. Results: Out of 1,753 pts with MCL, 36 (2%) had evidence of CNS involvement, including 4 pts with CNS involvement at initial MCL diagnosis. Baseline characteristics of pts with CNS involvement (CNS MCL group) and those without CNS involvement (control group) are shown in Table 1. At MCL diagnosis, non-CNS extranodal involvement was seen in 30 (83%) pts in the CNS MCL group (24 pts with 1 site and 6 pts with ≥ 2 sites), with bone marrow being the most common extranodal site of involvement (n=24, 67%). For the control group, 54 (75%) pts had extranodal involvement (44 pts with 1 site and 10 pts with ≥ 2 sites), and bone marrow was also the most common extranodal site of involvement (n=50, 69%). Notably, advanced stage disease (stage 3-4) was more commonly seen in the CNS MCL group (n=32, 97%) than in the control group (n=59, 83%) (p=0.04) at MCL diagnosis. Blastoid variant was present in a higher proportion of pts in the CNS MCL group (n=11, 31%) compared to the control group (n=8, 11%) (p=0.02). The CNS MCL group also presented with a higher median serum LDH at diagnosis (239 U/L [range 153-1901] vs. 187 U/L [range 124-588], p=0.02), and higher Ki-67 (40% [range 15-100] vs. 30% [range 10-90], p=0.04) compared to the control group. The most common frontline treatment regimen was anthracycline-based therapies (i.e. R-CHOP, Nordic regimen, R-hyperCVAD) for both groups (58% in CNS MCL group and 56% in control group). 14 (39%) pts in the CNS MCL group underwent autologous stem cell transplant in CR1 vs. 31 pts (43%) in the control group. Similar use of rituximab maintenance was seen in both groups (31% in CNS MCL group and 25% in control group). Median total lines of therapy from initial MCL diagnosis was 3 (range 1-9) in CNS MCL group and 2 (range 1-9) in the control group. The median follow-up from MCL diagnosis was 134 months (95% CI:119-163) for the entire cohort. Median OS from MCL diagnosis was 50.3 months (95% CI: 20.9-71.1) for the CNS MCL group compared to 97.1 months (95% CI: 82.6-192.7; p=<0.001) for the control group (Figure 1). Median time from MCL diagnosis to CNS involvement was 25 months (range 0-167). Median OS from CNS involvement was 4.7 months (95% CI: 2.3-6.7). At last follow up, 31 (86%) pts were deceased from the CNS MCL group, compared to 38 (52%) pts in the control group. For the CNS MCL group, the causes of death were CNS lymphoma in 10 (32%) pts, systemic lymphoma in 9 (29%) pts, treatment-related complication in 7 (23%) pts, and other/unknown in 5 (16%) pts. For the control group, the causes of death were systemic lymphoma in 15 (39%) pts, treatment-related in 2 (5%) pts, and other/unknown in 21 (55%) pts. Conclusion: In pts with MCL, CNS involvement is associated with worse outcomes as evident by a shorter median OS from initial MCL diagnosis (50 months vs. 97 months). Involvement of the CNS by lymphoma is an important contributor for the shorter OS as suggested by the median OS of only 5 months from CNS involvement. Advanced stage, blastoid variant, elevated LDH, and elevated Ki67 at MCL diagnosis were features more commonly seen in the CNS MCL cohort. Validation of risk factors at initial MCL diagnosis associated with CNS involvement and exploring the role of CNS prophylaxis are important topics for further investigation. Figure 1 Figure 1. Disclosures Paludo: Karyopharm: Research Funding. Wang: Novartis: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Research Funding; InnoCare: Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding. Bennani: Purdue Pharma: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Vividion: Other: Advisory Board; Kymera: Other: Advisory Board; Verastem: Other: Advisory Board. Nowakowski: Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene, NanoString Technologies, MorphoSys: Research Funding. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Habermann: Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Incyte: Other: Scientific Advisory Board; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding.

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Fertility Rates in Young Hodgkin Lymphoma Survivors: A Danish Nationwide Cohort Study of 769 Patients

Blood ◽

10.1182/blood-2019-122642 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2841-2841

Author(s):

Andreas Kiesbye Øvlisen ◽

Lasse H. Jakobsen ◽

Kristian Hay Kragholm ◽

Martin Hutchings ◽

Henrik Frederiksen ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Index Date ◽

Cox Regression ◽

Fertility Rates ◽

Grant Funding ◽

Advisory Committees ◽

First Child ◽

Funding Research

Introduction: The vast majority of young adults with Hodgkin lymphoma (HL) are cured by contemporary first line treatments. Treatment-related long-term toxicities can have a negative impact on survivorship and the risk of infertility may be particularly pertinent to young HL survivors. This study aimed to investigate the fertility rate (rate of first child after index date) over time in patients with HL compared to the matched controls. Methods: All Danish patients with HL, including classical and lymphocyte predominant HL, diagnosed in the period 2000-2015 were identified in the Danish Lymphoma Registry. Patients aged 18-40 years at diagnosis with documented complete remission after first line therapy were included. Patient data were merged with the Danish Fertility Database and the Medical Register of Births and Deaths. For each HL patient, five random Danish citizens alive at the index date of the HL patient were matched on birth date, sex, and parenthood status (categorical; with children vs without children at the index date). Follow-up was measured from 9 months post diagnosis (index date) until the time of first child, relapse, death, or censoring, whichever came first. Patients with progression/relapse within the first 9 months after diagnosis were excluded. Cumulative incidences of first living child after the index date were computed for the entire cohort and stratified on sex using the Aalen-Johansen estimator with death or relapse before first child after index date as competing events. Cox regression was used to compare the rates of first child of HL patients and matched controls by clinical subgroups and estimated for males and females separately. Results: A total of 769 HL patients were included (male:female ratio 1.2, median age 30 years) and median follow-up was 9.9 years. The mean numbers of children per person at start of follow-up were similar in patients and matched controls (female HL patients 0.64 vs matched controls 0.63 children per individual; male HL patients 0.56 vs matched controls 0.54 children per individual). At the end of follow-up, average numbers of children were higher in male and female HL patients (female HL patients 1.22 children per individual; matched control 1.14 children per individual) and males (HL patients 1.00 children per individual; matched controls 0.92 children per individual). The cumulative incidence of first child after index date in female HL patients was lower during the first three years of follow-up compared to the matched controls. However, beyond three years of follow-up the cumulative incidences of first child after index date were similar (Figure 1A). Among male HL patients the cumulative incidence of first child after index date was higher than that of the matched controls throughout the entire follow-up (Figure 1B). Overall, fertility rates were higher in HL patients (males, 36.7 per 1,000 person years; females, 41.7 per 1,000 person years) as compared to the matched controls (males, 24.2 per 1,000 person years; females, 33.0 per 1,000 person years). The Cox regression showed that both male and female patients with HL had higher fertility rates as compared to matched controls (males, HR 1.5, p-value < 0.001; females, HR 1.2, p-value = 0.012; Table 1). This was also observed in specific clinical subgroups, i.e. ages 18-30 years, CCI 0, no children prior to diagnosis, and limited stage disease. Moreover, among patients receiving 6+ cycles of chemotherapy, fertility rates were not lower than expected (Table 1). Conclusion: The fertility rates for long-term HL survivors without progression/relapse were higher than in matched controls, in particular for male HL patients. Elevated fertility rates as compared to the matched controls were observed for lower age (<30 years), limited stage disease, and for patients without children at the time of diagnosis. No clinical subgroup did significantly decrease the fertility rates. Disclosures Hutchings: Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Novartis: Research Funding. Frederiksen:Abbvie: Research Funding; Alexion: Research Funding; Gilead: Research Funding; Novartis: Research Funding; Janssen: Research Funding. Eloranta:Karolinska Institutet: Other: coordinator for a public-private real world evidence; Janssen Pharmaceuticals.: Other: project coordinator for a public-private real world evidence. Glimelius:Janssen Pharmaceuticals: Honoraria. Ekstroem Smedby:Janssen Cilag: Honoraria, Other: Grant funding, Research Funding; Celgene: Honoraria, Other: Grant funding, Research Funding; Takeda: Honoraria, Other: Grant funding, Research Funding. El-Galaly:Roche: Employment, Other: Travel support; Takeda: Other: Travel support.

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