scholarly journals Treatment Decision Making in AML: Factors of Importance to Clinicians, AML Patients and Their Family

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3498-3498
Author(s):  
Thomas W. LeBlanc ◽  
Roland B. Walter ◽  
Loriana Hernandez-Aldama ◽  
Kate Sully ◽  
Timothy J Bell ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Decision Making ◽  
Board Of Directors ◽  
Research Funding ◽  
Treatment Decision ◽  
Employment Equity ◽  
Advisory Committees ◽  
Trade Offs ◽  
Equity Ownership

INTRODUCTION: Acute myeloid leukemia (AML) is a rare hematologic cancer primarily affecting older people, with a median age at diagnosis of 67 years old (Almeida & Ramos, 2016). Heterogeneity in the presentation, functional status and presence of comorbidities among AML patients presents unique challenges for treatment. Intensive chemotherapy (IC), although the best option for prolonging survival, carries a risk of early death and other trade-offs, including significant time spent in the hospital. The toxicity of IC treatment and the requirement for prolonged hospitalizations may negatively affect patients' physical functioning and health-related quality of life (HRQoL). Novel, low-intensity treatments can be administered in the clinic and may pose less risk of immediate toxicities but may be associated with reduced efficacy. Each patient and family will approach these trade-offs differently, yet few studies examine the process of shared decision-making in AML. We aimed to better understand this process by eliciting patient/family and physician narratives about expectations and attitudes towards AML treatments. METHODS: Ten physicians in the US (n=4), UK (n=3) and Canada (n=3) and 12 AML patients (all US) and a member of their family took part in an individual, 60-minute qualitative telephone interview. Further interviews are scheduled and any additional data at the time of presentation will also be reported. The interviews followed a semi-structured guide comprising open-ended questions. The overarching aim of the interviews was to understand the value of living longer for AML patients who are not candidates for standard IC and to explore the treatment decision process from the patient, family and physician perspective. During the interviews, each participant (patient, family member or physician) completed a rating exercise in which they were asked to rate a list of pre-defined factors (9-10 factors) on a scale of 0 (not at all important) to 3 (very important) to determine their importance in AML treatment decisions. As well as providing a numerical rating for each factor, each participant was asked why they selected their rating and which three factors they would consider the most important. RESULTS: Across all three groups, relief in AML symptoms (namely fatigue and pain), longer survival and better QoL were equally considered the three most important factors when making a treatment decision. All three groups described the interaction between QoL and longer survival, explaining that any increase in survival would be important, but only if QoL (time spent with family, maintaining hobbies/interests) was maintained or improved. Physician's advice was also important to AML patients when making decisions regarding treatment. Other treatment-related factors within the rating task were rated as very important for at least a subset of patients, with no factors widely considered to be of limited importance. All participants noted that while relief of AML symptoms, longer survival and quality of life were all important, these had to be considered in light of treatment side effects and risk of infection. Likelihood of being hospitalized was important to family members, as they wanted to spend quality time at home with their loved ones, while patients and physicians considered hospitalization as an inevitable consequence of the disease and treatment. All participants reported that AML patients would consider taking any form of treatment if suitable and effective, regardless of the mode of administration. However, it was acknowledged that oral treatments would be more convenient and less invasive. The relative importance of location of care/treatment delivery was influenced by proximity to resources and whether the participant was based in an urban or rural setting. The ability to receive treatment at home was considered beneficial. CONCLUSIONS: The results from this rating exercise and qualitative interviews showed convergence across all stakeholders, indicating that AML patients, family and physicians have similar priorities regarding treatment decisions, prioritizing symptom relief, survival, and quality of life. The predominant treatment pathways in AML each require trade-offs in these factors, demonstrating the importance of shared decision making in ensuring the most appropriate treatment is selected for a given individual, in accordance with their values, goals, and preferences. Figure Disclosures LeBlanc: Jazz Pharmaceuticals: Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Heron: Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy; Flatiron: Consultancy; NINR/NIH: Research Funding; Duke University: Research Funding; Astra Zeneca: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Medtronic: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; Celgene: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc: Consultancy; American Cancer Society: Research Funding; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CareVive: Consultancy. Walter:Seattle Genetics: Research Funding; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Aptevo Therapeutics: Consultancy, Research Funding; Argenx BVBA: Consultancy; Astellas: Consultancy; BioLineRx: Consultancy; BiVictriX: Consultancy; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding; Race Oncology: Consultancy. Hernandez-Aldama:Pfizer Inc: Consultancy. Sully:Pfizer Inc: Consultancy; Adelphi Values Ltd: Employment. Bell:Pfizer Inc.: Employment, Equity Ownership. Johnson:Pfizer Inc: Consultancy; Adelphi Values Ltd: Employment. Peloquin:Pfizer Inc: Employment, Equity Ownership. Gater:Pfizer Inc: Consultancy; Adelphi Values Ltd: Employment. Welch:Pfizer Inc: Employment, Equity Ownership. O'Hara:Adelphi Values Ltd: Employment; Pfizer Inc: Consultancy. Russell:Astellas: Consultancy, Honoraria, Speakers Bureau; Pfizer Inc: Consultancy, Honoraria, Speakers Bureau; Jazz: Consultancy, Honoraria, Speakers Bureau; DSI: Consultancy, Honoraria, Speakers Bureau. Horikoshi:Pfizer Inc: Consultancy. Maze:Pfizer Inc: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals IPH4102; An Anti-KIR3DL2 Monoclonal Antibody in Refractory Sezary Syndrome: Results from a Multicenter Phase 1 Trial

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 684-684 ◽  
Author(s):  
Martine Bagot ◽  
Pierluigi Porcu ◽  
Basem M. William ◽  
Maxime Battistella ◽  
Maarten Vermeer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Monoclonal Antibody ◽  
Board Of Directors ◽  
Research Funding ◽  
Phase 1 ◽  
Employment Equity ◽  
Advisory Committees ◽  
Multicenter Phase ◽  
Equity Ownership

Abstract Aims: Sezary Syndrome (SS) is the most aggressive form of cutaneous T cell lymphoma (CTCL), characterized with high blood involvement and expression of Killer cell immunoglobulin like receptor 3DL2 (KIR3DL2). IPH4102 is a first-in-class monoclonal antibody that targets KIR3DL2. Very limited effective treatment options are available for SS patients with refractory disease. We conducted a phase 1 study testing IPH4102 in patients with refractory CTCL. Here we report results from the SS subset. Methods: IPH4102-101 study is a multicenter phase I trial composed of a dose escalation and cohort expansion portions that evaluated IPH4102 in patients with refractory CTCL. Key eligibility criteria included failure of ≥ 2 prior systemic therapies. KIR3DL2 testing was performed for all patients at baseline and at different time points throughout the study. IPH4102 was given Q1w x 4 weeks, followed by Q2w x 10 weeks then Q4w until disease progression or unacceptable toxicity. Primary endpoint is safety. Main 2ry endpoints include best global response (BGR) using the Olsen criteria, progression-free survival (PFS), duration of response (DOR), quality of life (QOL) and biomarker analyses. Results: The study included 35 SS patients, 20 in the dose escalation and 15 in the cohort expansion, with a median age of 70 years (37-90). Median time from initial SS diagnosis to starting IPH4012 was 22.8 months. Nineteen patients (54%) received IPH4102 as ≥ 4th line of systemic therapy and 7 (20%) were previously treated with mogamulizumab. Thirteen patients (37%) had lymph node involvement as per investigator assessment and based on radiological examination while 7 patients (20%) had evidence of large cell transformation. KIR3DL2 expression was observed in either skin or blood in 33 patients (94%) and in both in 28 patients (80%). Most common adverse events (AEs) were asthenia (26%), peripheral edema (26%), and fatigue (23%), which were all grade 1-2. Possibly related grade ≥ 3 AEs were observed in 7 patients (20%), and only 2 patients (6%) stopped treatment for an AE. Table 1 shows BGR and response by compartment. Overall response rate was 42.9% [95% CI: 28.0% - 59.1%], with median time to response of 4.8 months. Median DOR and PFS were 5.6 months [95% CI: 3.2-not reached] and 12.8 months [95% CI: 8.1-not reached], respectively. Mogamulizumab pretreated patients showed BGR, median DOR and PFS of 42.9%, 13.8 and 20.9 months, respectively. Quality of life assessment was performed using the Pruritus VAS score andSkinDex29. Patients with CR, PR or SD showed marked improvement overtime of all evaluated parameters including SkinDex29 global, symptoms, emotional, and functional scores. Biomarker analysis showed progressive decrease in CD4/CD8 ratio in responding patients. The decrease of KIR3DL2+ expressing cells in skin evaluated by immunohistochemistry at week 5 and 14 was able to predict BGR (AUC=0.749, 0.714, respectively). Figure 1 shows reduction in KIR3DL2 expressing cells at week 5 and week 14 in a patient who had PR as BGR. To date, 9 patients are still ongoing treatment. Updated clinical and correlative research analyses will be presented at the meeting. Conclusions: IPH4102 is highly effective in patients with refractory SS. It induces meaningful clinical activity and improves quality of life placing it as an encouraging treatment option for these patients. Further development in SS and other T-cell malignancies is underway. Disclosures Bagot: Actelion: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees. Porcu:Innate Pharma: Consultancy. Khodadoust:Innate Pharma: Research Funding. Sicard:Innate Pharma: Employment, Equity Ownership. Azim:Innate Pharma: Employment, Equity Ownership. Kim:miRagen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon Pharma: Consultancy, Research Funding; Galderma: Research Funding; Tetralogic: Research Funding; Neumedicine: Consultancy, Research Funding; Soligenix: Research Funding; Portola: Research Funding; Forty Seven Inc: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Venetoclax Improves Quality of Life for Patients with Elapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4858-4858 ◽  
Author(s):  
Tara Cochrane ◽  
Tatiana Chagorova ◽  
Tadeusz Robak ◽  
Su-Peng Yeh ◽  
Evgeny Nikitin ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Eortc Qlq ◽  
The Impact

Abstract INTRODUCTION: Patients with chronic lymphocytic leukemia (CLL) have significantly decreased health related quality of life (HRQoL), particularly related to severe and progressive fatigue. Side effects of chemotherapies and the emotional burden of living with an often poor prognosis disease also negatively impact patient HRQoL. Venetoclax, an oral agent that targets the anti-apoptotic protein BCL2, has demonstrated high rates of deep and durable response in patients with relapsed/refractory (R/R) CLL, including those with 17p deletions, and has been shown to facilitate clinically relevant improvement in several key aspects of functioning and HRQoL. We evaluated the impact of venetoclax monotherapy on the quality of life of patients with R/R CLL. METHODS: VENICE II is an ongoing open-label, phase 3b, multicenter study (NCT02980731) that assessed patient-reported HRQoL in patients who were ≥18 years old with R/R CLL, including those with 17p deletion, TP53 mutations, and/or prior experience with B-cell receptor pathway inhibitor-containing (BCRi) therapy, treated with venetoclax monotherapy (5-week dose-titration, starting at 20mg once daily, then increased weekly to 50 mg, 100 mg, 200 mg, and 400 mg, followed by 400mg once daily). The primary endpoint was the mean change from baseline to Week 48 in the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) subscale. HRQoL subscales analyzed included: Global Health Status, Role Functioning, Emotional Functioning, Cognitive Functioning, Social Functioning, and Fatigue. The impact on QoL was also assessed on the CLL Module (EORTC QLQ-CLL16). Relevance of mean changes in HRQoL measures from baseline were analyzed based on minimum important difference (MID); a 5-10 point change was defined as MID, and >10 points was considered clinically meaningful.(Osoba, D., et al. J Clin Oncol. 1998;16:139-44. Osoba, D., et al. Qual Life Res. 1994;3:353-64.) Safety and adverse events (AEs) were also monitored. RESULTS: As of the data cutoff, April 30, 2018, the median time on study was 28 weeks (range: 1 - 73) and the median time on therapy was 23 weeks (range: 0.1 - 69) in this ongoing study. Of the 169 treated patients, 70% were male; the median age was 65 years (range: 24 - 86). Among those with available data, 17p deletions and TP53 mutations were confirmed in 34% (41/122) and 38% (19/50) of patients, respectively. Overall, 38%, 20%, and 42% of patients had one, two, and three (or more) prior lines of therapy respectively; 21% of patients had prior BCRi therapy. Clinically meaningful improvements from baseline were observed by week 12 and were sustained through week 48 in the EORTC-QLQ-C30 global health status and the role function, social function, and fatigue subscales (Table and Figure 1A) and EORTC-QLQ-CLL16 future health and disease effect subscales (Table and Figure 1B). Eighty-two percent of patients had at least 1 AE; most commonly observed AEs (≥10% of patients) were neutropenia (35%), diarrhea (17%), thrombocytopenia (15%), anemia (12%), nausea (12%), and upper respiratory infection (11%). Twenty-eight percent of patients had a serious AE, of which the most common were pneumonia (5%), febrile neutropenia (4%) and pyrexia (3%). Five percent of patients discontinued the study due to an AE. CONCLUSIONS: Preliminary data from this ongoing study suggest that patients with R/R CLL experienced improvement in several key aspects of functioning and quality of life with venetoclax monotherapy within the first 12 weeks which is sustained over time. Venetoclax monotherapy was well tolerated in R/R CLL patients. These findings are consistent with previous studies of R/R CLL patients who received venetoclax monotherapy. Disclosures Cochrane: Janssen: Membership on an entity's Board of Directors or advisory committees; Cilag: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Calgene: Honoraria; Amgen: Honoraria; Novartis: Honoraria; MSD: Honoraria. Robak:AbbVie, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Nikitin:AbbVie, Inc: Speakers Bureau. Breuleux:Roche: Employment, Equity Ownership; Gilead: Equity Ownership; Basilea: Patents & Royalties; Novartis: Patents & Royalties. Masud:AbbVie, Inc: Employment, Equity Ownership. Sail:AbbVie, Inc: Employment, Equity Ownership. Komlosi:AbbVie, Inc: Employment, Equity Ownership. Anderson:Walter and Eliza Hall: Employment, Patents & Royalties; AbbVie, Inc: Research Funding; Genentech: Research Funding.

scholarly journals Understanding Clinician and Patient Preferences about Novel Agents in Chronic Lymphocytic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4730-4730
Author(s):  
Hannah Le ◽  
Trudy Pendergraft ◽  
Svea K. Wahlstrom ◽  
Kellie Ryan ◽  
Laura Sarokin ◽  
...  
Keyword(s):  
Decision Making ◽  
Board Of Directors ◽  
Dose Reduction ◽  
Research Funding ◽  
Treatment Decision ◽  
Novel Agents ◽  
Employment Equity ◽  
Advisory Committees ◽  
Treatment Decision Making ◽  
Equity Ownership

Introduction: Chronic lymphocytic leukemia (CLL) is an indolent disease most common in elderly adults. While chemo-immunotherapy is a standard first-line (1L) therapy for physically fit patients, treatment options for all CLL patients have greatly increased with the approval of novel agents. Thus, treatment decision-making in CLL has become more challenging, as physicians and patients must consider the risk-benefit trade-offs inherent to treatment options. Yet, little is known about the attitudes, beliefs, and preferences that underlie treatment decision-making in real-world settings for CLL. We aimed to elucidate oncologist/hematologist (ONC) and patient (PT) preferences about key attributes associated with novel CLL treatments using qualitative methods. Methods: In May 2019, we conducted in-depth interviews with 10 ONCs who each manage ≥20 CLL PTs with systemic therapy, prescribe novel agents for CLL, and spend at least 50% of their time in direct PT care. In addition, we interviewed 10 adult PTs with CLL. A commercial healthcare database was used to recruit ONCs, and PTs were recruited via advocacy groups. A trained moderator used a semi-structured interview guide to facilitate interviews focused on attributes influencing CLL treatment decision-making; for ONCs, interviews also asked about factors used to decide whether to treat a PT (vs. active surveillance [AS]). A standardized qualitative coding procedure (content analysis) was used to identify key themes emerging from interview responses. Descriptive statistics are reported to summarize the results. Results: ONCs had a median of 10.5 (range: 7-30) years in practice; most (n=7, 70%) reported working in an academic setting. The decision on whether or not to initiate treatment (vs. AS) depended on multiple factors, primarily symptoms, with patient motivation, health status, and treatment goals playing a lesser role. All ONCs prioritized efficacy when selecting a CLL treatment; progression-free survival (PFS; n=9) and overall survival (OS; n=7) were the top 2 metrics considered. Shorter treatment duration was considered when preferred by the PT or where adherence was a concern. ONCs perceived novel CLL therapies to be effective and well-tolerated; tumor lysis syndrome (TLS; n=8), atrial fibrillation (n=7), and diarrhea (n=7) were among the adverse events (AEs) most often cited as being a concern. ONCs perceived dose reduction as a way to mitigate certain types of AEs. All non-academic ONCs (n=3, 100%) presented one specific treatment to their PTs, but most academic ONCs (n=5, 71%) also discussed options with PTs, even if one specific treatment was recommended. Among PTs, the median age was 62.5 (range: 54-78) years, and most (n=7, 70%) were female. Four (40%) PTs were in 1L, with 4 (40%) in second/later lines (2L+), of treatment for their CLL; 2 (20%) PTs were in AS. Efficacy (described in terms of long-term remission) and concern about the impact of AEs on quality of life (QoL) were of greatest importance to PTs in choosing a treatment. Half reported that their ONC presented a specific recommendation for 1L treatment. Among 1L and 2L+ PTs (n=8), most (n=6, 75%) reported that ONCs did not provide detailed information about AEs associated with their CLL treatment. Across all PTs, cardiac issues and TLS (each, n=7) were the serious AEs most frequently reported as being of concern; other potential AEs, including joint pain (n=5) and brittle fingernails (n=2), were also cited as being of concern. Most PTs (n=9, 90%) expressed their preference for the convenience of oral over intravenous therapy. PTs who had a dose reduction (n=3) reported less apprehension about the potential impact on treatment efficacy than those who never had a dose reduction (n=7). Conclusions: While there was overlap between ONCs and PTs in the most concerning AEs, some PTs cited additional AEs due to the potential impact to their QoL. Regarding treatment preferences, PTs placed high importance on the impact of AEs on QoL, although this was of less importance to ONCs. Unlike ONCs, who viewed dose reductions as a means of resolving certain AEs, some PTs tended to question whether a dose reduction would diminish treatment efficacy. A better understanding of factors that influence treatment preferences may help facilitate ONC-PT communication when selecting novel CLL therapies. Future research should verify if these findings generalize to a representative PT population. Disclosures Le: AstraZeneca: Employment, Other: Stocks. Pendergraft:AstraZeneca: Employment, Equity Ownership. Wahlstrom:AstraZeneca: Employment, Equity Ownership. Ryan:AstraZeneca: Employment, Equity Ownership. Mulvihill:Kantar: Employment. Campbell:Kantar: Employment. Maculaitis:Kantar: Employment. LeBlanc:Helsinn: Consultancy; Jazz Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Duke University: Research Funding; Flatiron: Consultancy; Celgene: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; CareVive: Consultancy; Astra Zeneca: Consultancy, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; NINR/NIH: Research Funding; Pfizer Inc: Consultancy; American Cancer Society: Research Funding; Heron: Membership on an entity's Board of Directors or advisory committees; Medtronic: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Health-Related Quality of Life Among Patients with Relapsed or Refractory Multiple Myeloma Who Received Pomalidomide, Bortezomib, and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone - Results from the Phase 3 Optimismm Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1960-1960 ◽  
Author(s):  
Katja Weisel ◽  
Meletios A Dimopoulos ◽  
Philippe Moreau ◽  
Munci Yagci ◽  
Alessandra Larocca ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Research Funding ◽  
Low Dose ◽  
Employment Equity ◽  
Phase 3 ◽  
Advisory Committees ◽  
Treatment Groups ◽  
Equity Ownership

Abstract Introduction : A diagnosis of multiple myeloma (MM) has a substantial impact on health-related quality of life (HRQoL) due to associated symptoms, such as bone pain, infection, and fatigue. Furthermore, HRQoL deteriorates with each subsequent line of therapy. The phase 3 OPTIMISMM study (NCT01734928) demonstrated that pomalidomide, bortezomib, and low-dose dexamethasone (PVd) resulted in a significantly longer progression-free survival (PFS) and greater overall response rate (ORR) compared with bortezomib and low-dose dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM), all of whom had received prior treatment with lenalidomide. Given that HRQoL in RRMM is an important consideration, we conducted this analysis to evaluate the effect of PVd versus Vd on HRQoL in patients enrolled in the OPTIMISMM study. Methods : The OPTIMISMM study was a phase 3, multicenter, randomized, open-label study that enrolled adult RRMM patients who had received 1 to 3 prior anti-myeloma regimens including lenalidomide. Patients (N=559) were randomly assigned to receive PVd (n=281) or Vd (n=278) per 21-day treatment cycle until progression or treatment discontinuation. HRQoL was assessed as an exploratory endpoint using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30) questionnaire at Day 1 of each 21-day cycle prior to treatment administration and at the end of treatment. The primary domain of interest was the Global Health Status/QoL domain of the QLQ-C30. Analyses were performed in the HRQoL-evaluable population, which included randomized patients who completed the QLQ-C30 assessment at baseline and at least one post-baseline visit. Key primary analyses of PVd versus Vd on the global QoL domain of the QLQ-C30 included a longitudinal assessment of change from baseline using a mixed-model repeated measure (MMRM) approach; an assessment of the proportion of patients experiencing clinically meaningful deterioration (i.e., ≥10 points worsening from baseline) at pre-selected post-baseline visits; and an analysis of time to first clinically meaningful deterioration. Results : The HRQoL-evaluable population consisted of 240 patients in the PVd group and 209 in the Vd group; baseline characteristics were well-balanced between the treatment groups. HRQoL compliance rates based on the number of patients expected to complete the QLQ-C30 at each given visit exceeded 80% for most visits among both groups. Mean (SD) baseline scores for the global QoL domain of the QLQ-C30 were similar between groups (61.0 [23.2] in the PVd group and 63.5 [21.3] in the Vd group); these scores were maintained over time for both treatment groups, with no clinically meaningful differences observed between the treatment groups at any cycle (Figure 1). The MMRM analyses showed no clinically meaningful difference in global QoL of patients between the PVd group and the Vd group. There was also no significant difference observed in the proportion of patients who experienced clinically meaningful worsening in the global QoL domain between the treatment groups throughout the pre-selected post-baseline visits. The median time to the first clinically meaningful worsening was also similar between treatment groups: 3.0 months for the PVd group and 3.4 months for the Vd group, respectively (hazard ratio: 1.20; 95% confidence interval: 0.9456, 1.5151; p=0.1351; Figure 2 for when death was considered as an event); similar results were observed when death was censored. Conclusions: The results from this analysis of the OPTIMISMM study showed that the triplet regimen of PVd, which consisted of pomalidomide added to the doublet regimen of Vd, did not compromise HRQoL in lenalidomide-treated patients with RRMM. Overall, there were no clinically meaningful differences in the Global Health Status/QoL domain of the QLQ-C30 between treatment groups. These results are meaningful and provide further evidence of the clinical benefits of the addition of pomalidomide to Vd, which include significant improvements in PFS and ORR. Disclosures Weisel: Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria. Dimopoulos:Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Moreau:Amgen: 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; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: 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. Larocca:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria. Rodriguez Otero:Clínica Universidad de Navarra: Employment; Takeda: Consultancy; Bristol Myers Squibb: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Anttila:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hayden:Celgene: Honoraria; Jassen: Honoraria; Amgen: Honoraria. Krauth:Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Guo:Celgene Corporation: Consultancy. Purnomo:Celgene: Employment. Yu:Celgene: Employment, Equity Ownership. Grote:Celgene: Employment. Biyukov:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Richardson:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.

Understanding Treatment Preferences In Patients with Primary Immune Thrombocytopenia Contemplating Splenectomy: A Qualitative Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 392-392
Author(s):  
Karen Wang ◽  
Donald M. Arnold ◽  
Emmy Arnold ◽  
Nancy Heddle ◽  
John G. Kelton ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Decision Making ◽  
Board Of Directors ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Treatment Preferences ◽  
Advisory Committees ◽  
Primary Immune Thrombocytopenia ◽  
Data Saturation

Abstract Abstract 392 Introduction Primary immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder characterized by low platelet counts and an increased risk of bleeding. Recent consensus recommendations on ITP management (Provan, Blood 2010) emphasize the need for individualized treatment strategies based on patient preference; however little is known about which treatments patients prefer and why. Although splenectomy is most likely to induce a durable remission, uptake of splenectomy by patients and physicians is variable and a general tendency towards splenectomy avoidance has recently been observed. The objective of this study was to better understand patient preference and the factors affecting patients' decision for or against splenectomy. Methods We designed an exploratory qualitative interview study. Criterion sampling was used to identify eligible patients 18 years of age or older who were diagnosed with relapsed (lasting 3 – 12 months) or chronic (lasting longer than 12 months) primary ITP and who had been offered splenectomy as a treatment option by their physician, until data saturation was achieved. One to one, semi-structured interviews were conducted using an open-ended interview guide designed to investigate factors impacting splenectomy decision-making. Interview transcripts were coded independently in triplicate and interrater agreement was high. Major themes were identified from the data using a team analytic approach and audit trail. Results. Data saturation was achieved after 15 patients were interviewed; 6 were for splenectomy, 7 were against, and 2 were undecided. Patients were between the ages of 19 and 82 [median 43 years; interquartile range (IQR), 31 – 61] and 9 (60%) were female. Median duration of ITP was 49 months (IQR 13 – 113); patients had received a median of 2 prior treatments (IQR 2 – 3) and median platelet count at the time of the interview was 72 × 109/L (IQR 29 – 106). Four major themes were identified from the data about influences on treatment preferences: 1) patients' understanding of the ITP disease process; 2) patients' perception of the impact of ITP on their quality of life; 3) patients' understanding of the risks and benefits of treatments offered by their physician; and 4) patients' perception of splenectomy as a last resort. Patients were likely to accept splenectomy if their disease was perceived as having a negative impact on their quality of life. In general, patients had limited understanding of the cause of ITP and often misinterpreted the meaning of quoted probabilities of success with splenectomy. Conclusion Increased awareness of influences on patient treatment preferences will help physicians guide ITP patients through the complex decision-making process regarding splenectomy and can inform the design of decision-aids. Disclosures: Arnold: Hoffmann-LaRoche: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Talecris: Honoraria. Kelton:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees.

Ahead Study: A 3 Year Follow-up of 522 Severe and Moderate Hemophilia a Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3786-3786
Author(s):  
Johannes Oldenburg ◽  
Dimitrios Tsakiris ◽  
Cedric R. Hermans ◽  
RI Liesner ◽  
Kate Khair ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Hemophilia A ◽  
Employment Equity ◽  
Advisory Committees ◽  
Prophylaxis Group ◽  
Equity Ownership

Abstract Introduction: Long-term, real-world data on natural history of hemophilia A patients, safety and treatment outcome are still insufficient, particularly as far as the impact of bleeding on patient lives is concerned, as most of clinical trials and PASS studies are limited in study population size and length of follow-up, often no longer than 12 months. Methods: The AHEAD study is a non-interventional, prospective long-term cohort study including severe and moderate hemophilia A patients treated with ADVATE. Study endpoints include long-term joint health outcomes, annualized (joint) bleeding rates (ABR/AJBR), factor consumption, quality of life and safety data. Globally, AHEAD aims to evaluate data on approximately 1,000 patients, with a maximum follow-up period of up to 8 years. This interim data report includes 3 years of follow-up after study start. Results: The interim data report includes 522 patients from 21 countries (German study arm is not included in this analysis), for overall 1160 patient years. Of these, 334 completed year 1, 238 year 2 and 136 year 3 study visits. Median age at screening was 17 years (min-max: 0 - 78) and 57% of patients had severe HA (FVIII<1%); 78% were on prophylaxis, 21% were on demand (OD) and 1% on ITI treatment. The median ABRs in year 1, 2 and 3 were 1.2/1.2/1.9 respectively in patients on prophylaxis and 8.4/10.0/7.2, respectively in patients on OD. Median AJBRs were 0.9/0.9/1.0 in the prophylaxis group and 6.4/5.5/5.9 for patients on OD in the first three years of observation. Very similar data were reported taking only severe hemophilia A patients on prophylaxis into account (ABR: 1.9/1.7/2.5 and AJBR: 1.0/1.0/1.1) Overall, 56% of patients on prophylaxis and 32% of patients OD had an AJBR <1 in the first year, 54% and 33% in the second year and 52% and 22% in the third year. In the OD group about half of the patients had an AJBR ≥ 6, in the 3 years of follow up, while only 10% of patients in the prophylaxis group. Median annualized total dose in the prophylaxis group was consistently approximately 245,000IU while the FVIII consumption in the OD group was ranging from 26,000 to 47,000. Effectiveness of prophylaxis assessed by investigators was excellent/good in 93-96% of cases in the three years of observation. Functionality assessment using the hemophilia activity level (HAL) questionnaire showed a median summary score of 77.3-86.7 for patients on prophylaxis and 67.9-71.3 in patients OD over the 3 year follow up period. Differences of health related quality of life (HRQoL) as assessed by the SF-12 were found in the domain physical functioning (median score of 75-100 vs. 50-75 in patients on prophylaxis and OD, respectively) and role physical (median scores of 75 vs. 62.5-75 in patients on prophylaxis and OD, respectively). There were 7 treatment-related adverse events (AEs): 6 serious AEs (5 transient low titer inhibitors and 1 transient high titer inhibitor). The remaining non serious treatment-related adverse event was a mild allergic cutaneous reaction with rhinitis. All patients continued to receive ADVATE. Conclusion: Interim read-out of 3 year follow-up of patients enrolled in the AHEAD study show a clinically meaningful difference in ABR/AJBR, HAL, HRQoL of patients on prophylaxis or OD treatment. This study represents the largest cohort of hemophilia patients with the longest follow-up period. Disclosures Tsakiris: Baxalta, now part of Shire: Consultancy, Honoraria, Research Funding; Bayer Switzerland GmbH: Consultancy, Honoraria, Research Funding. Hermans:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies. Liesner:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BPL: Research Funding; Cangene: Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees. Khair:Pfizer: Research Funding; NovoNordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Study Investigator, Research Funding; Octapharma: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Study Investigator, Patents & Royalties, Research Funding, Speakers Bureau; Sobi/Biogen: Research Funding. Mazzucconi:Baxalta, now part of Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Speakers Bureau; NovoNordisk: Speakers Bureau; Pfizer: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Shire: Speakers Bureau. Steinitz-Trost:Baxalta, now part of Shire: Employment. Spotts:Shire: Employment. Reininger:Baxalta, now part of Shire: Employment, Equity Ownership. Gringeri:Shire: Employment, Equity Ownership.

scholarly journals Spk-9001: Adeno-Associated Virus Mediated Gene Transfer for Hemophilia B Achieves Sustained Mean Factor IX Activity Levels of >30% without Immunosuppression

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3-3 ◽  
Author(s):  
Lindsey A. George ◽  
Spencer K. Sullivan ◽  
Adam Giermasz ◽  
Jonathan M. Ducore ◽  
Jerome M. Teitel ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Transfer ◽  
Board Of Directors ◽  
Research Funding ◽  
Factor Ix ◽  
Hemophilia B ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background: Earlier data demonstrated long-term expression of factor IX (mean FIX:C ~5.1%) following AAV8-mediated gene transfer at 2 x1012 vg/kg in hemophilia B (Nathwani et al., 2014). While the clinical improvement imparted by stable FIX levels is clear, these levels of expression fall short of trough values obtained by long-acting FIX prophylaxis (Santagostino et al. 2016), and of natural history data suggesting that levels of ~12% are required to eliminate spontaneous hemarthroses (den Uijl et al. 2011). Achieving higher levels of FIX:C with dose escalation has not been possible without eliciting a dose-dependent, capsid-specific immune response that may prevent sustained expression and efficacy (Mingozzi et al. 2007, Monahan et al. 2015). We sought to develop a highly efficient vector capsid and expression cassette that could be administered at low doses to achieve hemostatic FIX expression without need for immunosuppression. Methods: The investigational product, SPK-9001, utilizes a bioengineered AAV capsid (Spark100) with liver specific tropism. The prevalence of neutralizing antibodies (NAb) to Spark100 among sampled hemophilia B sera was 40% (Anguela et al. 2015). The expression cassette is a codon-optimized, single-stranded transgene encoding FIX Padua, a naturally occurring variant with a single amino acid substitution (R338L) that confers ~8-fold greater specific activity compared to wild-type FIX (Simioni et al. 2009). Data on bleeding and factor infusions in the year prior to enrollment were retrospectively compiled. Laboratory values, bleeding frequency, FIX consumption, changes in activity and quality-of-life via Haem-A-QoL were prospectively evaluated after vector infusion. Results: We enrolled 9 subjects, of whom 2 failed screening for liver fibrosis and 7 were infused with SPK-9001 at a dose of 5 x1011 vg/kg. Infused subjects were adult males ages 18-52 years with baseline FIX:C </=2% and Spark100 NAb titer of <1:1 or 1:1. Table 1 outlines infused subject data with a follow up interval of >2-34 weeks after vector infusion. Figure 1 outlines subject vector-derived FIX:C for the first 12 weeks. There have been no vector or procedure related adverse events. Steady-state FIX expression is reached by 12 weeks after vector infusion, resulting in a mean FIX:C of 32.3% ±6.5%. To date, no subjects required immunosuppression or demonstrated evidence of a cytotoxic immune response (characterized by loss of FIX activity, elevation of transaminase values >/=1.5-times the upper limit of normal, and positive IFN-gammaELISPOT response to capsid peptides). No subjects developed a FIX inhibitor or demonstrated ELISPOT reactivity to the FIX (R338L) gene product. Subject 3 infused with FIX concentrate for a suspected ankle bleed 2 days after vector infusion. Beyond this, no subjects required factor or experienced any bleeding events. The 4 subjects previously maintained on prophylaxis safely stopped without break-through bleeding. As of today (cumulative 724 days post vector infusion), total factor consumption was reduced by 543,589 IU, tantamount to a cumulative savings of $1,182,298 USD.Six of 7 subjects report increased physical activity and improved quality of life. Conclusion: As of 8/4/2016, we report the highest and most consistent levels of sustained vector-derived FIX:C following FIX gene transfer. Levels of FIX:C achieved by SPK-9001 permitted termination of prophylaxis, prevention of bleeding, and nearly complete cessation of factor use. Despite the heterogeneity in subjects with respect to presence and extent of hemophilic arthropathy, age, and co-morbidities, consistency of transgene expression and clinical outcomes have been observed in all participants studied to date. A vector dose of 5x1011 vg/kg is the lowest dose currently reported in hemophilia gene transfer trials; the absence of any observed CD8+ T cell immune response supports the hypothesis that lowering the dose can reduce or eliminate the risk of a capsid-specific immune response and maximize efficacy. In summary, preliminary data suggest SPK-9001 safely and consistently produces sustained elevation in FIX:C levels sufficient to prevent spontaneous hemarthroses without the need for factor consumption or immunosuppression. Disclosures Ducore: Octapharama: Membership on an entity's Board of Directors or advisory committees; LFB: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Baxalta (Shire): Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Cuker:Biogen-Idec: Consultancy, Research Funding; T2 Biosystems: Research Funding; Genzyme: Consultancy; Stago: Consultancy; Amgen: Consultancy. McGuinn:Spark: Research Funding; Biogen: Research Funding; Novo Nordisk: Research Funding; Baxalta: Research Funding. Luk:Spark Therapeutics, Inc.: Employment. Wright:Spark Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties: SPK-9001. Chen:Spark Therapeutics, Inc.: Employment. Hui:Spark Therapeutics, Inc.: Employment. Wachtel:Spark Therapeutics, Inc.: Employment. Urich:Spark Therapeutics, Inc.: Employment. Takefman:Spark Therapeutics, Inc.: Employment. Couto:Spark Therapeutics, Inc.: Employment. Carr:Pfizer, Inc.: Research Funding. Anguela:Spark Therapeutics, Inc.: Employment, Patents & Royalties: SPK-9001. High:Spark Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties: SPK-9001.

Effect of Ruxolitinib On the Incidence of Splenectomy in Patients with Myelofibrosis: A Retrospective Analysis of Data From Ruxolitinib Clinical Trials.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2847-2847
Author(s):  
Srdan Verstovsek ◽  
Jean-Jacques Kiladjian ◽  
Ruben A. Mesa ◽  
Alessandro M. Vannucchi ◽  
Jason Gotlib ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Employment Equity ◽  
Massive Splenomegaly ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Phase Iii Studies

Abstract Abstract 2847 Background and Purpose: Myelofibrosis (MF) is a progressive Philadelphia-negative myeloproliferative neoplasm characterized by debilitating symptoms, massive splenomegaly, and anemia, which severely impairs quality of life. When medical therapy is not effective or tolerated, splenectomy may be required to ease symptoms in patients with symptomatic portal hypertension, massive splenomegaly, and/or frequent red blood cell transfusions (Barbui et al. J Clin Oncol. 2011;29:761–770). In a recent study (Tefferi et al. Mayo Clin Proc. 2012;87:25–33) up to 27% of patients diagnosed with MF eventually underwent splenectomy. However, splenectomy is associated with limited duration of symptom response, high rates of perioperative morbidity and mortality, and acceleration of hepatomegaly. Clinical studies in patients with MF have demonstrated that ruxolitinib, an oral JAK1/JAK2 inhibitor, provides significant and durable reductions in splenomegaly, the burden of MF-associated symptoms, and also improved quality of life. In this post hoc analysis of pooled data from these studies, we determined the incidence of splenectomy in patients treated with ruxolitinib and those who received placebo or best available therapy (BAT) to evaluate whether ruxolitinib therapy may affect the need for splenectomy. Methods: This analysis included patients who participated in the ruxolitinib phase I/II trial (N=153; Verstovsek et al. N Engl J Med. 2010;363:1117–1127); COMFORT-I, a phase III, 24-month placebo-controlled trial of ruxolitinib (N=309; Verstovsek et al. N Engl J Med. 2012;366:799–807); and COMFORT-II, a phase III, 48-month randomized trial comparing the effects of ruxolitinib and BAT (N=219; Harrison et al. N Engl J Med. 2012;366:787–798). Incidence of splenectomy while on treatment or during the protocol-specified follow-up period, adjusted for differences in the duration of follow up, was calculated for patients on ruxolitinib, placebo, or BAT. Results: As a result of the crossover rules and a higher discontinuation rate on the comparator arms in the phase III studies, mean follow-up duration for placebo (0.67 years) or BAT (0.95 years) overall was substantially shorter than mean follow-up duration for ruxolitinib (1.78 years). Baseline characteristics of the 14 patients who underwent splenectomy were as follows: median age=63 years; median time since initial diagnosis=7.8 years; median spleen length (n=13): 17.0 cm (range: 0–28.0 cm); median spleen volume (in those with measurement, n=11)=2924 cm3 (range: 1203–6807 cm3); IPSS high risk=50%, intermediate-2 risk=43%, intermediate-1=7%. Among patients originally randomized and treated with ruxolitinib, the incidence of splenectomy was 1.1 events per 100 patient years (Table). For patients treated with placebo or BAT in the phase III studies, the incidence of splenectomy was approximately three times higher at 2.9 events per 100 patient years, despite the fact that patients on placebo or BAT were allowed to crossover to ruxolitinib if they had worsening symptomatic splenomegaly. Conclusions: Although limited by small numbers, results of this analysis suggest that ruxolitinib reduces the need for splenectomy in patients with MF. Because of crossover to ruxolitinib and higher discontinuation rates in placebo and BAT, follow-up duration was shorter in these treatment arms compared with ruxolitinib. Further, ruxolitinib treatment in crossover patients may have prevented progression of symptomatic splenomegaly in some patients who may have otherwise become candidates for splenectomy. Our analysis may underestimate the true incidence of splenectomy among patients not receiving ruxolitinib therapy and therefore, the relative reduction in splenectomy rate in patients receiving this therapy. Longer-term follow up will better define the splenectomy rate in ruxolitinib-treated patients. Disclosures: Verstovsek: Incyte Corporation: Research Funding. Kiladjian:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Gotlib:Incyte Corporation: Consultancy, Honoraria, Support for travel to meeting for the study or other purposes from Incyte Other. Kantarjian:Incyte: grant support Other. Sirulnik:Novartis: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sandor:Incyte Corporation: An employee of Incyte and receiving stock options as part of his compensation Other, Employment. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding.

scholarly journals Rapid and Robust Mobilization of CD34+ HSCs without G-CSF Following Administration of Mgta-145 Alone or in Combination with Plerixafor

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1961-1961
Author(s):  
John F. DiPersio ◽  
Jonathan Hoggatt ◽  
Steven Devine ◽  
Lukasz Biernat ◽  
Haley Howell ◽  
...  
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Board Of Directors ◽  
Preliminary Data ◽  
Research Funding ◽  
Fold Change ◽  
Employment Equity ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Equity Ownership

Background Granulocyte colony-stimulating factor (G-CSF) is the standard of care for mobilization of hematopoietic stem cells (HSCs). G-CSF requires 4-7 days of injections and often multiple aphereses to acquire sufficient CD34+ cells for transplant. The number of CD34+ HSCs mobilized can be variable and patients who fail to mobilize enough CD34+ cells are treated with the combination of G-CSF plus plerixafor. G-CSF use is associated with bone pain, nausea, headaches, fatigue, rare episodes of splenic rupture, and is contraindicated for patients with autoimmune and sickle cell disease. MGTA-145 (GroβT) is a CXCR2 agonist. MGTA-145, in combination with plerixafor, a CXCR4 inhibitor, has the potential to rapidly and reliably mobilize robust numbers of HSCs with a single dose and same-day apheresis for transplant that is free from G-CSF. MGTA-145 plus plerixafor work synergistically to rapidly mobilize HSCs in both mice and non-human primates (Hoggatt, Cell 2018; Goncalves, Blood 2018). Based on these data, Magenta initiated a Phase 1 dose-escalating study to evaluate the safety, PK and PD of MGTA-145 as a single agent and in combination with plerixafor. Methods This study consists of four parts. In Part A, healthy volunteers were dosed with MGTA-145 (0.0075 - 0.3 mg/kg) or placebo. In Part B, MGTA-145 dose levels from Part A were selected for use in combination with a clinically approved dose of plerixafor. In Part C, a single dose MGTA-145 plus plerixafor will be administered on day 1 and day 2. In Part D, MGTA-145 plus plerixafor will be administered followed by apheresis. Results MGTA-145 monotherapy was well tolerated in all subjects dosed (Table 1) with no significant adverse events. Some subjects experienced mild (Grade 1) transient lower back pain that dissipated within minutes. In the ongoing study, the combination of MGTA-145 with plerixafor was well tolerated, with some donors experiencing Grade 1 and 2 gastrointestinal adverse events commonly observed with plerixafor alone. Pharmacokinetic (PK) exposure and maximum plasma concentrations increased dose proportionally and were not affected by plerixafor (Fig 1A). Monotherapy of MGTA-145 resulted in an immediate increase in neutrophils (Fig 1B) and release of plasma MMP-9 (Fig 1C). Neutrophil mobilization plateaued within 1-hour post MGTA-145 at doses greater than 0.03 mg/kg. This plateau was followed by a rebound of neutrophil mobilization which correlated with re-expression of CXCR2 and presence of MGTA-145 at pharmacologically active levels. Markers of neutrophil activation were relatively unchanged (<2-fold vs baseline). A rapid and statistically significant increase in CD34+ cells occurred @ 0.03 and 0.075 mg/kg of MGTA-145 (p < 0.01) relative to placebo with peak mobilization (Fig 1D) 30 minutes post MGTA-145 (7-fold above baseline @ 0.03 mg/kg). To date, the combination of MGTA-145 plus plerixafor mobilized >20/µl CD34s in 92% (11/12) subjects compared to 50% (2/4) subjects receiving plerixafor alone. Preliminary data show that there was a significant increase in fold change relative to baseline in CD34+ cells (27x vs 13x) and phenotypic CD34+CD90+CD45RA- HSCs (38x vs 22x) mobilized by MGTA-145 with plerixafor. Mobilized CD34+ cells were detectable at 15 minutes with peak mobilization shifted 2 - 4 hours earlier for the combination vs plerixafor alone (4 - 6h vs 8 - 12h). Detailed results of single dose administration of MGTA-145 and plerixafor given on one day as well as also on two sequential days will be presented along with fully characterized graft analysis post apheresis from subjects given MGTA-145 and plerixafor. Conclusions MGTA-145 is safe and well tolerated, as a monotherapy and in combination with plerixafor and induced rapid and robust mobilization of significant numbers of HSCs with a single dose in all subjects to date. Kinetics of CD34+ cell mobilization for the combination was immediate (4x increase vs no change for plerixafor alone @ 15 min) suggesting the mechanism of action of MGTA-145 plus plerixafor is different from plerixafor alone. Preliminary data demonstrate that MGTA-145 when combined with plerixafor results in a significant increase in CD34+ fold change relative to plerixafor alone. Magenta Therapeutics intends to develop MGTA-145 as a first line mobilization product for blood cancers, autoimmune and genetic diseases and plans a Phase 2 study in multiple myeloma and non-Hodgkin lymphoma in 2020. Disclosures DiPersio: Magenta Therapeutics: Equity Ownership; NeoImmune Tech: Research Funding; Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Consultancy; Incyte: Consultancy, Research Funding; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; WUGEN: Equity Ownership, Patents & Royalties, Research Funding; Macrogenics: Research Funding, Speakers Bureau; Bioline Rx: Research Funding, Speakers Bureau; Celgene: Consultancy; Amphivena Therapeutics: Consultancy, Research Funding. Hoggatt:Magenta Therapeutics: Consultancy, Equity Ownership, Research Funding. Devine:Kiadis Pharma: Other: Protocol development (via institution); Bristol Myers: Other: Grant for monitoring support & travel support; Magenta Therapeutics: Other: Travel support for advisory board; My employer (National Marrow Donor Program) has equity interest in Magenta. Biernat:Medpace, Inc.: Employment. Howell:Magenta Therapeutics: Employment, Equity Ownership. Schmelmer:Magenta Therapeutics: Employment, Equity Ownership. Neale:Magenta Therapeutics: Employment, Equity Ownership. Boitano:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Cooke:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Goncalves:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Raffel:Magenta Therapeutics: Employment, Equity Ownership. Falahee:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Morrow:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Davis:Magenta Therapeutics: Employment, Equity Ownership.

scholarly journals Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3129-3129
Author(s):  
Hans C. Lee ◽  
Sikander Ailawadhi ◽  
Cristina Gasparetto ◽  
Sundar Jagannath ◽  
Robert M. Rifkin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Causes Of Death ◽  
Age Groups ◽  
Treatment Patterns ◽  
Age Group ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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