A Ruxolitinib Individual Supply Program for Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Abstract Abstract 5170 Background: There are currently no approved, effective drug therapies for myelofibrosis (MF). Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, has recently demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life in 2 phase 3 studies in patients with MF. Both studies met their primary endpoint of the proportion of patients with ≥35% reduction in spleen volume at 24 weeks (COMFORT-I) and at 48 weeks (COMFORT-II): 41.9% vs 0.7% (ruxolitinib vs placebo, P <.0001) and 28.5% vs 0% (ruxolitinib vs best available therapy, P <.0001), respectively. The most common grade ≥3 hematologic adverse events (AEs) were thrombocytopenia and anemia, which were manageable and rarely led to discontinuation (COMFORT-I: n=1 each; COMFORT-II: thrombocytopenia, n=1; anemia, n=0). Because of the limited available treatment options and medical need, ruxolitinib has been made available through an individual supply program (ISP) outside the United States. Methods: Patients with PMF, PPV-MF or PET-MF who are determined by their physicians to be in need of treatment are considered for eligibility, irrespective of JAK2 mutation status. As in the COMFORT studies, the starting dose of ruxolitinib is determined on the basis of baseline platelet count and can be adjusted for efficacy and safety. Dose changes during treatment are registered, and AEs and serious AEs (SAEs) are monitored throughout the study. Results: To date, 231 patients have been screened at more than 150 study sites in 28 countries, including Canada, Australia, and locations in Europe, Latin America, the Middle East, and Asia. The baseline characteristics for patients whose requests for access were approved/enrolled (n=200) and denied/pending (n=31) are shown below (Table). The patient characteristics are generally similar to those expected in the overall MF patient population. To date, the proportion of patients with the JAK2V617F mutation enrolled in this ISP (68.5%) is higher than that for the general MF population (50–60%) and may reflect the tendency of physicians to include more JAK2V617F-positive patients in the ISP, even though ruxolitinib has demonstrated comparable efficacy in both patient types (Verstovsek S, et al. N Engl J Med. 2010;363(12):1117–1127). Thrombocytopenia and herpes zoster were each reported as an AE in 1 patient, and no SAEs have been reported. Conclusions: Ruxolitinib is currently the only drug to have completed phase 3 studies for the treatment of MF and has garnered a substantial number of requests for access through the individual supply program. Disclosures: Barosi: Novartis: Consultancy. Cervantes:Bristol-Myers-Squibb: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Panagiotidis:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Janssen: Research Funding; GSK: Honoraria. Perez:Novartis: Employment. Orlando-Harper:Novartis: Employment. Martin:Novartis Pharma AG: Employment. Willenbacher:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AESCA: Honoraria, Research Funding. Ojeda:Novartis: Consultancy. Gisslinger:Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau; Aop-Orphan: Speakers Bureau. Knoops:Novartis: Consultancy.

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The Interaction between IPSS Score and JAK2 Mutation Identifies Patients at Different Vascular Risk in Primary Myelofibrosis

Blood ◽

10.1182/blood-2021-145116 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 236-236

Author(s):

Tiziano Barbui ◽

Arianna Ghirardi ◽

Alessandra Carobbio ◽

Arianna Masciulli ◽

Greta Carioli ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Board Of Directors ◽

Research Funding ◽

Primary Myelofibrosis ◽

Vascular Risk ◽

Advisory Committees ◽

Jak2 Mutation ◽

Thrombosis Rate

Abstract BACKGROUND The rate of major arterial and venous thrombosis in primary myelofibrosis (PMF) and post-ET (PET) and post-PV (PPV) secondary myelofibrosis has been evaluated in a limited number of studies. In the present paper we describe the clinical epidemiology of thrombosis in a large series of patients with overt PMF and PPV/PET MF looking at the rate and risk factors. Moreover, we report findings on thrombosis rate in two cohorts of patients treated with Hydroxyurea (HU) or Ruxolitinib (Ruxo). METHODS Patients were registered in the European Registry for Myeloproliferative Neoplasms (ERNEST). This project, promoted by the European LeukemiaNet, is coordinated by FROM - Foundation for Research, Papa Giovanni XXIII Hospital, Bergamo (Italy) and supported by Novartis through a research collaboration . Patients were diagnosed in 6 Centers from Italy, Spain and Sweden, between Jan, 2001 and Dec, 2012, with the required follow-up information. Patients (n= 1010) with PMF (n=584, 59%), PET-MF (n=207, 20%) and PPV-MF (n=219, 21%) were evaluated for incident thrombosis as primary endpoint. Considering death as a competitive event, uni-and multivariate analyses were performed by applying Fine & Gray competing-risk regression models. RESULTS After a median follow-up of 3.8 years (IQR: 1.8-7.1) from diagnosis, 108 thromboses (10.7%) occurred, for an overall incidence rate of 2.0% pts-yr (95% CI: 1.7-2.5). Arterial thromboses were found in 50 patients (46.3%) including cerebral (n=21, 19.4%), myocardial infarction (n=13, 12.0%) and peripheral events (n=9, 8.3%). Venous thromboses were 58 (53.7%), of which 25 (23.0%) were DVT ± PE and 11 (10.2%) were splanchnic. Thrombosis rate was 1.91, 1.60 and 2.79% pts-yr in PMF, PET-MF and PPV-MF, respectively. In univariate analysis, factors significantly associated with an increased thrombotic risk in PMF were age (p=0.013) and the presence of the JAK2 mutation (p=0.003); in addition, a significant higher proportion of PMF patients at low and intermediate-1 vs intermediate-2 or high risk IPSS score, had thrombosis during the follow-up (p=0.008). In multivariate analysis, only JAK2 mutation retained statistical significance (SHR=3.12, 95% CI: 1.40-6.94, p=0.005). Conversely, neither in univariate nor in multivariable analysis, significant risk factors were not found.To investigate the possible interaction of IPSS score and JAK2 mutation we created a model whose results are presented in Fig. 1A: the cumulative incidence function (CIF) of thrombosis was significantly lower in patients with JAK2 wild-type and intermediate-2 or high IPSS score (CIF: 4% projected at 10 years; SHR=1 [reference category]), while patients at the highest risk for thrombosis harbored JAK2 mutation and were categorized at low or intermediate-1 by IPSS score (CIF: 20% projected at 10 years, SHR=7.13, p=0.008). Of note, thrombosis had a significant impact on mortality. After adjusting for sex, age, year of diagnosis, type of MF and IPPS, HR was 1.51, (95% CI. 1.15-1.98, p=0.003).The influence of drug exposure to incident thrombosis was investigated in two cohorts of 559 consecutive patients exposed to HU (n=470) or to Ruxo (n=89), median treatment 2.6 and 3.0 years, respectively. HU- compared to Ruxo-treated patients were older (median age 67 vs. 63 years, p=0.001), more frequently triple negatives (12% vs. 2%, p=0.036), less splenomegalic (spleen length >10 cm: 30% vs. 88%, p <.001) and less symptomatic (49% vs. 79%, p=0.031). Of note, median time from MF diagnosis to therapy start in Ruxo group was 4 years, whereas patients started HU at MF diagnosis. In 56 of 89 Ruxo-treated patients (62.9%), the drug was given after a prior HU therapy. The thrombosis rate from the time of initiation of therapy was 2.40% pts-yr (95% CI 1.78-3.24) under HU and 1.28% pts-yr (95% CI 0.48-3.41) under Ruxo (CIF curves in Fig. 1B). In multivariate analysis corrected for MF type, DIPPS at first drug administration, JAK2 mutation and time from MF diagnosis, exposure to Ruxo showed a non-significant trend towards a protection of approximately 70% compared to HU (SHR=0.33, 95% CI: 0.08-1.32, p=0.117). CONCLUSION IPSS score, in addition to the survival risk assessment, may be useful, if associated with the JAK2 mutation, to recognize patients at vascular risk and to suggest appropriate anti-thrombotic prophylaxis. The trend towards a benefit of Ruxo, compared to HU, warrants a study in larger case series. Figure 1 Figure 1. Disclosures Barbui: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Passamonti: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Speakers Bureau. Vannucchi: Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures.

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An Individual Patient Supply Program for Ruxolitinib for the Treatment of Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF).

Blood ◽

10.1182/blood.v120.21.2844.2844 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2844-2844

Author(s):

Giovanni Barosi ◽

Mohan Agarwal ◽

Sonja Zweegman ◽

Wolfgang Willenbacher ◽

Sima Pakstyte ◽

...

Keyword(s):

Polycythemia Vera ◽

Board Of Directors ◽

Essential Thrombocythemia ◽

Research Funding ◽

Jak2 V617f ◽

Primary Myelofibrosis ◽

Jak2 V617f Mutation ◽

Phase 3 ◽

Advisory Committees ◽

The Us

Abstract Abstract 2844 Background: Myeloproliferative neoplasms, including PMF, PET-MF, and PPV-MF, are a group of clonal stem cell–derived diseases characterized by bone marrow fibrosis, splenomegaly, and debilitating constitutional symptoms. Ruxolitinib (rux), a potent oral JAK1 & 2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life in 2 phase 3 studies (COMFORT-I and -II). Due to unmet medical need, rux has been made available through an individual patient supply program (IPSP) outside the US. Methods: Patients (pts) with PMF, PPV-MF, or PET-MF requiring treatment (as determined by their physician) and classified as high-, intermediate (int)-2–, or int-1–risk with an enlarged spleen were evaluated for eligibility on an individual basis by the sponsor, irrespective of JAK2 mutation status. The starting dose of rux was determined on the basis of baseline platelet count (15 or 20 mg twice daily for pts with platelet counts of 100–200 × 109/L and > 200 × 109/L, respectively) and can be adjusted for efficacy and safety. Dose changes during treatment, adverse events (AEs), and serious AEs (SAEs) are registered throughout the program. Results: To date, 1339 requests have been received from > 800 physicians in 48 countries, including locations in Europe, Latin America, the Middle East, and Asia. The baseline characteristics are shown in the Table for pts whose requests for access were approved (n = 1240). Drug resupply requests are received every ≈ 3 months. Follow-up information, based on the first resupply request, was available for 381/639 (60%) of the pts who were enrolled in the program prior to February 2012; 303 (80%) remain on rux therapy, 37 (10%) have discontinued, 11 (3%) died, and 30 (8%) did not initiate therapy. Spleen response was available for 247 pts (decreased, n = 201; unchanged, n = 39; increased, n = 7). Changes in constitutional symptoms were available for 203 pts (decreased, n = 151; unchanged, n = 49; increased, n = 3). In pts enrolled in the IPSP undergoing rux treatment, most pts who had a decrease in spleen length also had a decrease in symptoms. Dose-modification information was available for 259 pts, of whom 44 had dose increases and 89 had dose decreases. Reasons for dose modifications included efficacy (n = 28), safety (n = 69), and other reasons (n = 36). Safety information was available for 266 pts; 75 reported significant AEs or SAEs as determined by investigators. Enrolled pt characteristics are generally similar to those expected in the overall MF pt population. Thus far, the proportion of pts enrolled in the IPSP with the JAK2 V617F mutation (73%) is higher than that for the general MF population (50%-60%). This may reflect a misconception that JAK inhibition is primarily effective in pts who have the JAK2 V617F mutation, when in fact rux has demonstrated similar efficacy in both pt types in the phase 1/2 251 study and the two phase 3 COMFORT trials. This may also be reflected in the higher proportion of PPV-MF pts in the IPSP than in the general MF population (28% vs 10%-15%), of whom 95% are JAK2 V617 F–positive. Conclusions: Considerable requests for access to rux have been received through the IPSP, highlighting the need for an effective treatment in pts with a range of IPSS risk-assessment scores. The demographics of the IPSP pts are similar to those expected in the overall MF population. Responses and safety patterns observed in the IPSP appear to be comparable to those from the COMFORT trials. Disclosures: Off Label Use: Jakafi™ (ruxolitinib) is indicated in the United States for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis and post–essential thrombocythemia myelofibrosis. In Canada, JAKAVI ® is indicated for the treatment of splenomegaly and/or its associated symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. This abstract reports on a clinical study conducted outside the US including patients of all risk categories. All patients have provided written informed consent. Zweegman:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Willenbacher:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Raymakers:Novartis: Consultancy. Cantoni:CSL Behring Switzerland: Research Funding; Robapharm/Pierre Fabre Oncology Switzerland: Research Funding; Janssen-Cilag Switzerland: Consultancy; Novartis Oncology Switzerland: Consultancy, Research Funding. Modi:Novartis Pharmaceuticals Corporation: Employment. Khan:Novartis: Employment. Perez:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Gisslinger:AOP Orphan Pharmaceuticals AG: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Lavie:Novartis: Membership on an entity's Board of Directors or advisory committees. Harrison:Sanofi Aventis: Honoraria; YM Bioscience: Consultancy, Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Research Funding.

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Evaluation and Comparison of Characteristics and Outcomes Among Frontline Multiple Myeloma (FLMM) Patients with and without Stem Cell Transplant Treatment

Blood ◽

10.1182/blood-2018-99-113176 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4738-4738 ◽

Cited By ~ 1

Author(s):

Ajai Chari ◽

Maneesha Mehra ◽

Mary Slavcev ◽

Annette Lam ◽

Ravi Potluri ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Patient Characteristics ◽

The United States ◽

Cell Transplant ◽

Real World Data ◽

Advisory Committees ◽

World Data

Abstract Background: High-dose therapy with autologous stem cell transplantation (SCT) is a standard treatment option in FLMM patients who are ≤65 years of age. Few studies have examined the real-world patient characteristics and outcomes associated with those who receive an SCT compared with non-SCT patients. Aims: To use real-world data to characterize patients with FLMM who received SCT compared with those who did not receive SCT, and determine their overall survival (OS). Methods: Data were extracted from 3 real-world data sources from the United States: Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked (January 2007 to December 2014), OPTUM™ Commercial Claims (January 2000 to March 2017), and OPTUM™ Electronic Medical Records (EMR; January 2007 to March 2016) databases. Patients with 1) an index MM diagnosis on or after 1 January 2007 who 2) had known gender and medical prescription coverage at the time of diagnosis, 3) had a 1-year look-back period prior to index diagnosis, 4) had no prior cancers in the 1-year period prior to index diagnosis, and 5) had at least 1 line of treatment were included. SCT patients were defined as those who received an SCT at any time during their follow-up. Patient characteristics such as age (at index diagnosis), gender, and comorbidities (180 days before start of first line of therapy [LOT1]) were descriptively compared. OS was evaluated from the start of LOT1 using the Kaplan-Meier method and multivariable Cox regression analyses. Results: A total of 9,323 patients were analyzed, comprising 1,599 SCT (17.2%) and 7,724 (82.8%) non-SCT patients. Patient characteristics and OS are summarized in the Table. Descriptive differences in patient characteristics were observed between SCT and non-SCT patients, including median age at start of frontline treatment, gender, and incidences of baseline comorbidities. In terms of survival outcomes, median OS was not reached (NR; 95% confidence interval [CI], 91.8-not estimable [NE]) for SCT patients compared with 45.1 (95% CI, 43.1-46.8) months for non-SCT patients. Age at index diagnosis, gender, time to and year of treatment initiation, and presence of baseline comorbidities were significantly associated with OS. Accounting for differences in these patient characteristics, the adjusted hazard ratio (HR) for OS in non-SCT versus SCT patients was 2.29 (95% CI, 2.01-2.61; P <0.0001). Among the different age subgroups (<65, 65-74, and ≥75 years of age), the OS benefit for SCT versus non-SCT was maintained across these subgroups (Figure). Conclusions: In a real-world setting, FLMM patients who received SCT were younger and had lower rates of several comorbidities at baseline compared with non-SCT patients. A significant OS benefit was observed among patients who had received SCT, underlying the need for more effective treatment options in patients who do not receive SCT. Disclosures Chari: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array Biopharma: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; The Binding Site: Consultancy. Mehra:Janssen Global Services, LLC: Employment. Slavcev:Janssen Global Services, LLC: Employment. Lam:Janssen Global Services, LLC: Employment. Potluri:SmartAnalyst Inc.: Employment. Kaufman:Abbvie: Consultancy; Roche: Consultancy; BMS: Consultancy; Janssen: Consultancy; Karyopharm: Other: data monitoring committee.

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Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) with Acute Myeloid Leukemia (AML): Princess Margaret Cancer Centre Experience

Blood ◽

10.1182/blood-2019-125449 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2609-2609

Author(s):

Muhned Alhumaid ◽

Georgina S Daher-Reyes ◽

Wilson Lam ◽

Arjun Law ◽

Tracy Murphy ◽

...

Keyword(s):

Board Of Directors ◽

Older Patients ◽

Myeloid Leukemia ◽

Research Funding ◽

Age Groups ◽

Treatment Strategies ◽

Patient Characteristics ◽

Cancer Center ◽

Advisory Committees ◽

Disease Behavior

Introduction: Clinical outcomes of acute myeloid leukemia (AML) in adolescents and young adults (AYA) are rarely reported as an isolated subgroup. Treatments vary little across age groups, and treatment intensity depends upon comorbid conditions and performance status. Optimal treatment strategies focused on disease behavior, biological factors, and the distinct needs of this subset of AML patients remain elusive. The purpose of this retrospective analysis is to determine the characteristics and outcomes of AYA AML patients treated at a specialized adult leukemia cancer center in comparison to older adults with AML (40-60 years). Methods: A retrospective analysis was performed on all patients treated at Princess Margaret Cancer Center from 2008-2018. Patients with acute promyelocytic leukemia were excluded. Clinical characteristics, treatment strategies, and survival outcomes were recorded for all patients. Overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier product-limit method and the impact of covariates were assessed using the Log-rank test. Finally, we compared the outcomes of AYA patients treated at our centre between 2015-2018 with older patients. Results: A total of 175 patients aged 18-39 were identified. Patient characteristics are shown in (Table 1). Cytogenetic were available in 163 patients. Based on MRC criteria, 27 (16%) were favorable risk, intermediate in 95 (54%), adverse in 39 (22%), and missing/failed in 14(8%). NPM1 status was available in 110 patients of whom 38 (35%) were positive. FLT3-ITD was available in 67 patients with 24 (36%) positive. Both mutations were present in 13 (54%) patients. There were no significant differences in terms of risk stratification based on cytogenetic and molecular markers based on age (18-29 vs.30-39) (P= 0.98). Most patients 172 (98%) received induction, 157 (91%) with 3+7, and 15 (9%) with FLAG-IDA. Complete remission (CR) was achieved in 133 (77%) after first induction [120 (76%) after 3+7 and 11 (73%) after FLAG-IDA]. Induction related mortality was low (2%). Of the 39 who did not achieve CR, thirty-four patients received re-induction (13 FLAG-IDA, 16 NOVE-HiDAC, 5 others) with CR in 21 (62%). Overall, 154 (89.5%) achieved CR1. Sixty-four (42%) proceeded to hematopoietic stem cell transplantation (HSCT) in CR1. 59 (38%) patients relapsed in CR1 with 8 (12%) relapsing post HSCT. Fifty-five (5 post HSCT) patients received reinduction with 30 (51%) (2 after HSCT) achieving CR2. Fifteen patients received HSCT in CR2. OS and DFS at 2 years were 62% (95% CI 0.53-0.69) and 50% (95% CI 0.41-0.57), respectively. Stratified by cytogenetic risk, OS was 81% for favorable risk, 61% for intermediate, and 50% for adverse risk (P=0.0001), respectively. DFS in these groups was 85%, 57%, and 46 % (P=0.0025), respectively. We further compared outcomes in the 18-29y and 30-39y age groups. The OS was 61.9% compared to 62.5% (P=0.91) and DFS of 52.1% compared to 47% (P=0.65) respectively. On univariate analysis for OS and DFS, cytogenetic risk stratification was the only significant variable (P=0.0004 and P=0.0042). We then compared the outcomes 67 sequential patients aged I8-39 treated from 2014-2018, with those of 176 sequential patients aged 40-60 treated during the same period (table 2). OS at 2 years was not statistically higher in the younger group compared to the older group (66.7% vs. 61.2%, P=0.372). While relapse rate was lower in older patients (15.5% vs. 22.6%, P=0.093), NRM was higher in older patients (29.7% vs. 18.8%,P=0.094). Conclusion: AYA pts. occupy a unique niche amongst AML as a whole. While treatment responses have improved in general, there may be potential for further gains in these patients. Increased tolerance for more intense treatment strategies as well as the incorporation of novel agents into standard treatment protocols may provide a means to optimize care in AYA patients. Finally, research is needed to elucidate biological mechanisms and predictors of disease behavior instead of arbitrary, age-stratified treatment schema. Disclosures McNamara: Novartis Pharmaceutical Canada Inc.: Consultancy. Schimmer:Jazz Pharmaceuticals: Consultancy; Medivir Pharmaceuticals: Research Funding; Novartis Pharmaceuticals: Consultancy; Otsuka Pharmaceuticals: Consultancy. Schuh:Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva Canada Innovation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Maze:Pfizer Inc: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yee:Astellas: Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Astex: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MedImmune: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffman La Roche: Research Funding. Minden:Trillium Therapetuics: Other: licensing agreement. Gupta:Incyte: Honoraria, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Efficacy and Safety of Ravulizumab in Older Patients Aged >65 Years with Paroxysmal Nocturnal Hemoglobinuria in the 301 and 302 Phase 3 Extension Studies

Blood ◽

10.1182/blood-2020-140777 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 42-43

Author(s):

Regis Peffault De Latour ◽

Jeffrey Szer ◽

Austin Kulasekararaj ◽

Jin Seok Kim ◽

Caroline I. Piatek ◽

...

Keyword(s):

Board Of Directors ◽

Older Patients ◽

Research Funding ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Complement Inhibitor ◽

Efficacy And Safety ◽

Phase 3 ◽

Advisory Committees ◽

Treatment Naïve ◽

Secondary Endpoints

Background: In the two largest phase 3 studies in patients with paroxysmal nocturnal hemoglobinuria (PNH), ravulizumab given every 8 weeks was noninferior to eculizumab given every 2 weeks across all efficacy endpoints. Data on efficacy and safety of ravulizumab in patients aged >65 years with PNH are limited. Aims: To compare the efficacy and safety of ravulizumab in patients with PNH aged >65 years with those aged ≤65 years. Methods: The population included patients from two phase 3 studies that assessed ravulizumab vs eculizumab in complement-inhibitor-naïve (301; NCT02946463) and -experienced (302; NCT03056040) adults with PNH. In study 301, patients were aged ≥18 years with a confirmed PNH diagnosis by flow cytometry and had a lactate dehydrogenase (LDH) level ≥1.5x upper limit of normal (ULN; 246U/L). In study 302, patients were aged ≥18 years with a confirmed PNH diagnosis by flow cytometry, were clinically stable on eculizumab having received ≥6 months of treatment and had a LDH level ≤1.5x ULN. Patients were randomized to either ravulizumab or eculizumab for 26 weeks after which all received ravulizumab up to 52 weeks. This prespecified analysis stratified patients by age: ≤65 or >65 years. Primary endpoints included percentage change in LDH from baseline to weeks 26 and 52, percentage of patients achieving LDH-normalization (LDH-N; LDH levels: ≤1x ULN) at weeks 26 and 52 and transfusion avoidance (TA) from baseline to weeks 26 and 52. Breakthrough hemolysis (BTH), hemoglobin (Hgb) stabilization and FACIT-fatigue score were secondary endpoints. Treatment emergent adverse events (TEAEs) were assessed as an indicator of safety. Results: A total of 58 patients aged >65 years and 383 patients aged ≤65 years were included. Disposition and medical history were similar among subgroups at baseline (Table 1). Results for primary and secondary endpoints for the two subgroups were comparable across studies and efficacy was maintained through 52 weeks. A higher proportion of treatment-experienced patients (>65 years) achieved all endpoints vs -naïve patients (Table 2). The percentage change in LDH levels from baseline to 26 and 52 weeks was similar between subgroups in study 301 (-66.5 to -80.0%) whereas in study 302, LDH levels remained stable in all subgroups up to 52 weeks (-3.7 to 22%). The percentage of patients achieving LDH-N in both studies at 26 and 52 weeks differed; 43.8-63.9% of patients aged ≤65 years achieved LDH-N compared with 21.4-77.8% of patients aged >65 years. A higher proportion of older treatment-experienced patients (57.1‒77.8%) achieved LDH-N compared with older treatment-naive patients (21.4‒50.0%) at 26 and 52 weeks. In patients aged ≤65 years in both studies, 63.7‒89.4% achieved TA. In the >65 years subgroup, 14.3‒50.0% of treatment-naive patients achieved TA whereas in study 302, 54.5‒72.7% of patients achieved TA. The number of BTH events was low, with no events reported in older patients to date. Hgb stabilization was consistent in the ≤65 year subgroup between the studies; a higher proportion of older patients in study 302 (45.5‒71.4%) achieved stabilized Hgb compared with older patients in study 301 (14.3‒35.3%). A clinically significant 3-point change was seen in FACIT-fatigue scores (indicating improvements in fatigue), with higher scores observed for ravulizumab in both subgroups (Figure 1). One patient discontinued the extension of study 301 due to lung cancer onset during the 26-week period and died following discontinuation. Headache was the most frequent TEAE. The incidence of TEAEs reported during ravulizumab treatment up to 52 weeks did not increase vs the 26-week period, with few events (Table 3) and no difference between subgroups. Conclusions: We present clinical outcomes in the largest cohort of patients with PNH (>65 years) on ravulizumab in a clinical trial setting to date. Ravulizumab was associated with similar efficacy and safety in both age subgroups and showed consistent and durable efficacy through 52 weeks of treatment. A higher proportion of patients in study 302 achieved all efficacy endpoints than in study 301, which can be due to patients' prior complement inhibitor experience. This observation was more evident in older patients. There were no BTH events in the older patients to date, and the number of infections in both subgroups was low. Ravulizumab was well tolerated in older patients with no additional safety concerns compared to younger patients. Disclosures Peffault De Latour: Apellis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Szer:Pfizer: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Prevail Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau. Kulasekararaj:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Piatek:Alexion Pharmaceuticals: Consultancy, Research Funding. Kulagin:Alexion Pharmaceuticals Inc.: Consultancy, Research Funding. Hill:Alexion Pharmaceuticals Inc.: Current Employment. Wang:Alexion Pharmaceuticals Inc.: Current Employment. Yu:Alexion Pharmaceuticals Inc.: Current Employment. Ogawa:Alexion Pharmaceuticals Inc.: Current Employment. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Lee:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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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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The Characteristics, Treatment Patterns, and Outcomes of Older Adults with Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-118660 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4463-4463

Author(s):

Mark A. Fiala ◽

Tanya M. Wildes ◽

Mark A. Schroeder ◽

Armin Ghobadi ◽

Keith E. Stockerl-Goldstein ◽

...

Keyword(s):

Older Adults ◽

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Performance Status ◽

Patient Characteristics ◽

Treatment Patterns ◽

Advisory Committees ◽

Improved Outcomes ◽

Immunomodulatory Drug

Abstract Background: Advances in the treatment for multiple myeloma (MM) have dramatically improved outcomes for younger patients. Older adults, particularly those 80 years of age or older at diagnosis, have seen more modest gains. MM incidence increases with age, and as more of the population is living later into life, the segment of the MM population over 80 will continue to grow. In this study, we sought to better understand the characteristics, treatment, and outcomes of older patients with MM. Methods: We identified all patients diagnosed with MM at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2007-2013 to determine incidence and outcomes. Subset analysis was then performed on patients included in the SEER-Medicare linked database who were enrolled in Medicare Parts A, B, and D to further explore patient characteristics and treatment patterns. Results: The incidence of MM increases over age, peaking after age 80. The annual incidence for those aged 65-69, 70-74, 75-79, 80-84 and 85+ was 24.4, 32.7, 39.5, 42.8 and 36.4 per 100,000, respectively. Based on 2010 US population estimates, approximately 4,500 new cases of MM were diagnosed annually 2007-2013 in patients age 80 or older. In that period, 8,093 cases, approximately 1,150 per year, were reported to SEER. The estimated median overall survival (OS) of these patients was 14 months (95% CI 13.2-14.8). The estimated relative 12 month survival was 58.9% (95% CI 57.4-60.4) compared to their peers without cancer. Of the 8,093 cases of MM reported to SEER during the study period, 2,385 were present in the SEER-Medicare linked dataset. Of these, 225 were identified as smoldering MM using a previously established algorithm (Fiala, et al, JCOCCI, 2018) and excluded leaving 2,160 for the analyses. The median age was 84 (range 80-100) and 55% were female. 81% were white, 13% black or African-American, and 6% another race. At disease presentation, 22% had claims indicating hypercalcemia, 61% renal failure or chronic kidney disease, 59% anemia, and 34% MM bone involvement. The estimated median OS was 13.4 months (95% CI 12.2-15.1). Only 52% of patients had claims indicating they received systemic MM treatment within 6 months post-diagnosis. Nearly all that did received novel agents; 38% received bortezomib-based treatment, 41% immunomodulatory drug (IMID)-based, and 14% both. The others received antineoplastic chemotherapies such as melphalan or cyclophosphamide. Interestingly, bortezomib utilization increased incrementally from 25% of patients treated in 2007 to 62% in 2013 while IMID utilization declined from 67% to 49%. The median OS of those receiving treatment was 21 months (95% CI 18.5-23.1) compared to 6.3 months (95% CI 5.3-7.3) for those who did not (p <0.0001). MM treatment was associated with a 26% decrease in hazard for death (aHR 0.74; 95% CI 0.67-0.82; p < 0.0001) independent of age, race, gender, poverty, comorbidities, and proxy measures of performance status. Outcomes improved for patients in more recent years; the hazard for death decreased by 3% (HR 0.97; 95% CI 0.94-0.99; p = 0.0096) each year 2007-2013. This can be attributed to increasing treatment rates. In 2007, only 41% of patients received treatment compared to 61% in 2013. After controlling for MM treatment, the year of diagnosis was no longer a significant predictor of survival. Conclusions: The outcomes of patients with MM over 80 years old are still relatively poor; nearly half of the patients do not receive systemic treatment and for those who do the median OS is just 21 months. The population over 80, when MM incidence peaks, is projected to triple over the next few decades. It is imperative that we improve our understanding of the needs of this vulnerable subgroup of patients of MM. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Efficacy Outcomes of Treatments for Double Relapsed/Refractory Follicular Lymphoma (R/R FL): A Systematic Literature Review

Blood ◽

10.1182/blood-2020-136228 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 42-43

Author(s):

Brad S. Kahl ◽

Anik R. Patel ◽

Omer Zaidi ◽

Sonya J. Snedecor ◽

Anna G. Purdum

Keyword(s):

Clinical Trials ◽

Follicular Lymphoma ◽

Board Of Directors ◽

Clinical Data ◽

Research Funding ◽

Treatment Options ◽

Unmet Need ◽

Progression Free Survival ◽

Disease Stage ◽

Advisory Committees

ABSTRACT Introduction: Patients with indolent non-Hodgkin lymphomas (iNHL), including follicular lymphoma (FL), have high response to first-line treatment. However, retreatment is often required when relapses occur, and those with multiple relapses represent a patient population with an unmet need for effective treatment. Clinical data for several treatment options exist for the general relapsed and refractory (R/R) population; however, there are relatively fewer data specific to FL patients with ≥2 lines of prior treatment. This work systematically identified the available efficacy data in the double R/R FL population. Methods: The MEDLINE and EMBASE databases were searched through February 10, 2020. Studies were limited to interventional clinical trials of R/R FL patients (or mixed histologies with a predominance of FL) and articles published in English. Studies also must have reported one or more efficacy measures, such as overall response rate (ORR), complete response (CR), duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Potential interventions of interest were lenalidomide ± rituximab (R), duvelisib, ibrutinib, venetoclax, polatuzumab vedotin + R, obinutuzumab, copanlisib, umbralisib, idelalisib, and tazemetostat. Results: Of 35 publications examining treatment outcomes in R/R FL patients, only 14 (representing 5 unique clinical trials) were specific to the ≥ 2-line population. These trials were: CHRONOS Part B (copanlisib), DAWN (ibrutinib), DELTA (idelalisib), DYNAMO (duvelisib), and Morschhauser et al. 2019 (tazemetostat) and included a total of 605 participants. All studies used similar inclusion criteria, and patients included were similar in age (median 62-65), disease stage (III/IV), and ECOG score (0-2). Patients in the CHRONOS study had a median number of prior treatments of 2, whereas those in the DELTA study had 5. ORR ranged from 21% (ibrutinib) to 59% (copanlisib) (Table). The DoR ranged from 8.3 months in tazemetostat patients with EZH2 gene mutation to 19.4 months for ibrutinib. PFS ranged from 5.7 months in tazemetostat patients with wild-type EZH2 to 11.2 months for copanlisib. Median TTNT was only reported in the DAWN study (16 months). Conclusions: Very few clinical data exist reporting efficacy outcomes specific to the double R/R FL population. The limited data indicate that current treatments do not produce durable responses for most double R/R FL patients, demonstrating an unmet need. Further research is needed to fully understand the efficacy and safety of other potential interventions for this population. Disclosures Kahl: Genentech:Consultancy;Pharmacyclics LLC:Consultancy;AstraZeneca Pharmaceuticals LP:Consultancy, Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene Corporation:Consultancy;AbbVie:Consultancy;Roche Laboratories Inc:Consultancy;BeiGene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Acerta:Consultancy, Research Funding.Patel:Kite, a Gilead Company:Current Employment.Zaidi:BMS:Consultancy.Snedecor:Pharmerit - an OPEN Health Company:Other: Employment at consultancy paid by Kite Pharma to conduct this work.Purdum:Kite, a Gilead Company:Current Employment.

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Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenia (ITP) Treated with Romiplostim in Two Phase 3 Placebo-Controlled Clinical Trials.

Blood ◽

10.1182/blood.v114.22.891.891 ◽

2009 ◽

Vol 114 (22) ◽

pp. 891-891 ◽

Cited By ~ 1

Author(s):

Ilene Ceil Weitz ◽

Miguel A Sanz ◽

David H. Henry ◽

Martin Schipperus ◽

Bertrand Godeau ◽

...

Keyword(s):

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Rescue Medication ◽

Bleeding Event ◽

Bleeding Events ◽

Phase 3 ◽

Advisory Committees ◽

Platelet Counts ◽

Chronic Itp

Abstract Abstract 891 Background: Chronic Immune thrombocytopenia (ITP) is characterized by low platelet counts and increased risk of bleeding. Rescue medications used to treat or prevent bleeding produce transient increases in platelet counts but may be associated with additional toxicities and costs. Romiplostim, approved for the treatment of adult chronic ITP, is a TPO mimetic peptibody protein that increases platelet production. Previously published data from phase 3 romiplostim trials showed that despite the increased use of rescue medication in the placebo arm, patient (pt) incidence of bleeding was reduced in the romiplostim arm vs placebo arm: 15% vs 34% (p = 0.02) for bleeding of grade ≥2 severity and 7% vs 12% (p=0.36) for grade ≥3 severity. Objective: To evaluate the effects of romiplostim treatment on bleeding outcomes in the phase 3 placebo controlled studies in chronic ITP pts with and without previous splenectomy. Bleeding events were captured as adverse events making it difficult to identify a single event reported multiple times versus persistent or recurrent bleeding. Further, we have developed a composite endpoint, termed bleeding-related episodes (BREs), which combines bleeding events and rescue medication administration to account for use of rescue medications to prevent bleeding. Methods: Adults with chronic ITP and a mean baseline platelet count <30 × 109/L were eligible. The previously published studies were conducted separately in splenectomized and nonsplenectomized populations. Pts were randomized (2:1) to receive romiplostim or placebo by subcutaneous injection once weekly for 24 weeks, with dose adjustments to maintain platelet counts between 50-200 × 109/L. Rescue medications were permitted to treat or prevent bleeding and included immunoglobulins, platelet transfusions, corticosteroids, or an increase in dose or frequency of a concurrent ITP medication. A BRE was defined as an actual bleeding event and/or the use of rescue medication. To collapse related events into episodes, events (bleeding events and/or the use of rescue medication) that occurred concurrently or within 3 days of each other were considered a single BRE. Bleeding events beginning 7 or more days after the start of the initial bleeding event were considered a new BRE. To account for differences in time spent on-study, rates of BRE per 100 pt-weeks were calculated. Results: A total of 125 pts (41 placebo, 84 romiplostim) were enrolled in the two studies. Baseline characteristics were well-balanced between the placebo and romiplostim-treated groups. During the treatment period, the rate of BREs was lower in the romiplostim group than in the placebo group, and results were consistent between splenectomized and nonsplenectomized pts (Table). Across both studies, the rate of BREs was reduced by 55% in pts receiving romiplostim compared to those receiving placebo (95% CI, 41% to 65%). BREs were more frequent at platelet counts <50 × 109/L (Table). BREs associated with hospitalizations were less common among romiplostim- than placebo-treated pts, and occurred at platelet counts <50 × 109/L in 10 of 11 cases. Corticosteroids (58 romiplostim, 38 placebo) and immunoglobulins (30 romiplostim, 73 placebo), were the most commonly used rescue medications and the rate of BREs including immunoglobulins was reduced by 88% in pts receiving romiplostim compared to placebo. Conclusions: In adults with chronic ITP, romiplostim was associated with a significant reduction in BREs compared to placebo. There was a marked reduction in BREs requiring immunoglobulins in the romiplostim arm compared to the placebo arm. Results were comparable in splenectomized and nonsplenectomized populations. The platelet count for a BRE starting ≥1 day after a platelet count measurement was calculated from the 2 proximal weekly measurements. Disclosures: Weitz: Amgen Inc.: Speakers Bureau. Sanz:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Henry:Amgen Inc.: Research Funding, Speakers Bureau; Orthobiotech: Research Funding, Speakers Bureau; Watson Pharma: Research Funding, Speakers Bureau. Schipperus:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees. Godeau:Amgen Inc.: Consultancy, Research Funding; Laboratoire Français de Fractionnement et de Biotechnologies (LFB): Consultancy; Roche: Research Funding. Gleeson:Amgen Inc.: Consultancy, Research Funding. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

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