Pomalidomide (POM) Plus Low-Dose Dexamethasone (LoDEX) Improves Health-Related Quality Of Life (HRQoL) Vs High-Dose Dexamethasone (HiDEX) In Relapsed Refractory Multiple Myeloma (RRMM) Patients Enrolled In MM-003 Phase 3 Randomized Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2939-2939 ◽  
Author(s):  
Kevin W. Song ◽  
Meletios A. Dimopoulos ◽  
Katja Weisel ◽  
Michel Delforge ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Board Of Directors ◽  
Physical Functioning ◽  
Research Funding ◽  
Emotional Functioning ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background Pronounced symptoms, poor prognosis, and therapy exhaustion each affect HRQoL in RRMM patients. The MM-003, randomized, multicenter, open-label phase 3 trial reported that POM + LoDEX significantly extended median progression-free and overall survival vs HiDEX in RRMM patients who exhausted bortezomib (BORT) and lenalidomide (LEN), and progressed on their last treatment (San Miguel, EHA, 2013). Improved survival outcomes, treatment-related toxicity, and aging populations have placed an emphasis on HRQoL in RRMM. MM-003 is the first study to investigate HRQoL in RRMM patients treated with POM + LoDEX. Methods Patients were randomized 2:1 to receive 28-day cycles (C) of POM 4 mg D1-21 + LoDEX 40 mg (20 mg for patients aged > 75 years) weekly or HiDEX 40 mg (20 mg for patients aged > 75 years) D1-4, 9-12, and 17-20 until disease progression or unacceptable toxicity. HiDEX was chosen as the comparator to isolate the effects of POM as at the time of trial design, it was the standard salvage therapy for heavily pretreated patients. Time to meaningful worsening in HRQoL was analyzed for 5 predefined EORTC QLQ-C30 domains (Global Health Status, Physical Functioning, Fatigue, Emotional Functioning, and Pain) using the Kaplan-Meier method. A meaningful worsening was defined as a reduction in HRQoL equal to or greater than the domain-specific minimally important difference, calculated using the standard error of measurement. HRQoL was also evaluated cross-sectionally and longitudinally through a mixed effect model. Data from the September 7, 2012 data cut are presented below. Results 455 patients were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). 448 patients completed at least 1 QLQ-C30 questionnaire and were included in the HRQoL analysis. The median number of prior treatments was 5 (range, 2-17), and 82% were refractory to LEN and BORT. Median follow-up was 4.2 months. Analyses on time to clinically meaningful worsening showed that POM + LoDEX extended median time to meaningful worsening vs HiDEX for all the preselected domains (Table): Global Health Status (114 vs 85 days, P = .06), Physical Functioning (174 vs 106 days; P = .09), Fatigue (113 vs 60 days; P = .04), Emotional Functioning (190 vs 124 days; P = .02), and Pain (147 vs 113 days; P = .2). In the cross-sectional analysis, HRQoL scores were relatively better for POM + LoDEX vs HiDEX for all domains at every cycle. Statistically or marginally significant (P < .10) treatment differences were observed for Global Health Status (C2 and 4), Physical Functioning (C2, 3, and 4), Emotional Functioning (C3), and Fatigue (C2) domains. No statistically significant deteriorations from baseline were observed in the mean scores for the POM + LoDEX arm for any of the 5 domains at any treatment cycle. Such deteriorations were observed with HiDEX. These results were supported by a mixed effect model analysis. Data from the March 1, 2013 data cut will be presented at the meeting. Conclusions In heavily pretreated patients who exhausted BORT and LEN, POM + LoDEX resulted in better clinical outcomes and favorable HRQoL vs patients treated with HiDEX. POM + LoDEX should become a standard of care in relapsing patients as it has been proven to prolong and enhance the lives of RRMM patients. Disclosures: Song: Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: POM is approved in the US but not in Europe. Dimopoulos:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Weisel:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Delforge:Celgene: Honoraria. Karlin:Celgene: Export board committee Other, Honoraria; Janssen: Honoraria. Goldschmidt:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Moreau:Celgene: Honoraria, Speakers Bureau. Oriol:Celgene: Consultancy. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Knop:Celgene: Honoraria. Renner:Celgene: Consultancy, Honoraria, Travel support Other. Bahlis:Celgene: Consultancy, Honoraria, Research Funding. Amatya:Celgene: Consultancy. Yu:Celgene: Employment, Equity Ownership. Monzini:Celgene: Employment, Equity Ownership. Sternas:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment, Equity Ownership. San Miguel:Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Association of Changes in Transfusion Status with Changes in Health-Related Quality of Life of Real-World Patients with MDS Across Six Months of Treatment with Azacitidine

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2796-2796
Author(s):  
Chris L. Pashos ◽  
David L. Grinblatt ◽  
Mikkael A. Sekeres ◽  
Rami S. Komrokji ◽  
Mohit Narang ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Board Of Directors ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Transfusion Independence ◽  
Related Quality ◽  
Equity Ownership ◽  
Rbc Transfusion

Abstract Abstract 2796 Introduction: The health-related quality of life (HRQOL) of patients with myelodysplastic syndromes (MDS) is worse if they are red blood cell transfusion dependent (RBC TD) than if they are RBC transfusion independent (TI). Little is known whether a change in status from RBC TD to RBC TI is associated with improved HRQOL. This analysis characterized the HRQOL of real-world patients with MDS across 6 months of treatment with Azacitidine (AZA) by their RBC TD/TI status. Methods: Data were collected from AVIDA®, a prospective, US, community-based registry of patients treated with AZA. Patients with MDS who were originally RBC TD at baseline, and who received 56 days or more of AZA were analyzed. RBC TD, defined as having received > 1 RBC transfusion within 56 consecutive days, was determined and verified centrally. Clinicians provided data on patient demographics and clinical characteristics, including RBC transfusions. Patients reported HRQOL by completing the EORTC-QLQ-C30 instrument at baseline and quarterly thereafter. Summary statistics (e.g., mean scores and changes in scores) on global health status, five functional scales, and nine symptom/other scales were analyzed. Statistical significance was ascertained by ANOVA using SAS 9.1. Results: In the full AVIDA cohort, 328 MDS patients received at least 56 days of treatment with AZA, of whom 153 reported HRQOL data at baseline and at six months. At baseline, 85 of the 153 were RBC TD, while the rest were RBC TI. At six months, 41 of the 85 had become RBC TI, while 44 remained RBC TD. Global health status improved among those who became RBC TI, but declined among those who stayed RBC TD. Statistically significant and clinically meaningful (i.e., greater than 7 points) differences in change between baseline and 6 months also were seen in physical and role function, but not in emotional, cognitive or social function. Fatigue was the only symptom score in which changes were statistically significantly different between groups, with RBC TI patients reporting less fatigue, and RBC TD patients reporting more. Conclusions: Findings from AVIDA® indicate that HRQOL among RBC TD MDS patients treated with AZA improves significantly overall and on certain domains if they achieve RBC transfusion independence. The improved global health status; better physical and role functioning; and less fatigue associated with RBC TD patients achieving RBC transfusion independence should be recognized by US clinicians as they manage patients with MDS. Disclosures: Pashos: Celgene: Membership on an entity's Board of Directors or advisory committees. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees. Sekeres:Celgene: Consultancy, Honoraria, Speakers Bureau. Komrokji:Celgene: Honoraria, Research Funding, Speakers Bureau. Narang:Celgene: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership. Khan:Celgene: Employment, Equity Ownership.

Changes in Quality of Life and Disease-Related Symptoms in Patients with Polycythemia Vera Receiving Ruxolitinib or Best Available Therapy: RESPONSE Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 709-709
Author(s):  
Ruben Mesa ◽  
Srdan Verstovsek ◽  
Jean-Jacques Kiladjian ◽  
Martin Griesshammer ◽  
Tamas Masszi ◽  
...  
Keyword(s):  
Global Health ◽  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK/STAT activation and is associated with erythrocytosis and a broad symptom burden that may negatively impact patient quality of life (QoL). Hydroxyurea (HU) is often used as first-line therapy for high-risk patients but may not effectively control or reduce symptom burden. RESPONSE is a phase III trial comparing ruxolitinib (RUX) with best available therapy (BAT) in patients with PV who were intolerant of or resistant to HU according to modified European LeukemiaNet (ELN) criteria. The primary study endpoint (a composite of hematocrit control and ≥35% spleen volume reduction at Week 32) was achieved by 21% of patients in the RUX arm vs 1% in the BAT arm (P<0.0001); 77% of patients in the RUX arm achieved at least one component of the primary endpoint. The current analysis was conducted to evaluate the effect of RUX on PV-related symptoms and QoL measures in the RESPONSE trial. Methods : Patients with PV aged ≥18 years, resistant to or intolerant of HU (modified ELN criteria) with splenomegaly, and who required phlebotomy for hematocrit control were randomized 1:1 to receive open-label RUX 10 mg twice daily (BID) or BAT (administered based on investigator judgment). Dose adjustments were permitted (RUX, 5-mg BID increments [25 mg BID max]; BAT was adjusted per investigator judgment). Objectives of this analysis included assessment of improvement in symptom burden as assessed by patient-reported outcomes using the 14-item modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Patient Global Impression of Change. The 14-item MPN-SAF (graded from 0 [absent] to 10 [worst imaginable]) comprised symptoms related to cytokines (tiredness, itching, muscle ache, night sweats, and sweats while awake), hyperviscosity (vision problems, dizziness, concentration problems, headache, numbness/tingling, ringing in ears, and skin redness), and splenomegaly (abdominal discomfort and early satiety). Changes in total symptom score (TSS; maximum score = 140) and individual symptom scores from baseline to Week 32 were summarized by treatment group. For the EORTC QLQ-C30 Global Health Status/QOL score, the percentage of patients with a minimally important difference (MID) from baseline (10-point change) at Week 32 was summarized. Results : Overall, 222 patients were randomized (RUX, 110; BAT, 112). Median age (range) was similar between arms (RUX, 62.0 [34.0–90.0]; BAT, 60.0 [33.0–84.0]); the RUX and BAT arms were 60% and 71% male, respectively. At Week 32, a higher proportion of patients in the RUX vs the BAT arms had a ≥50% improvement in MPN-SAF TSS (49% vs 5%, respectively) and MPN-SAF symptom cluster scores (cytokine, 64% vs 11%; hyperviscosity, 37% vs 13%; splenomegaly, 62% vs 17%). Median percentage changes in individual symptom scores are presented in the Table. Mean changes from baseline at Week 32 on the 5 items of the PSIS indicated that the severity of pruritus and its interference on daily life improved with RUX (range, −1.5 to −2.2) and was unchanged/worsened with BAT (range, −0.1 to 0.3). Treatment with RUX vs BAT was associated with improved mean changes from baseline at Week 32 on EORTC QLQ-C30 symptom subscales, functional subscales, and Global Health Status/QOL (Table); 46% of RUX patients versus 10% of BAT patients achieved an MID in Global Health Status/QOL (Figure). At Week 32, RUX patients were more likely to rate their global impression of symptom changes as “very much improved” or “much improved” (67%) vs BAT patients (13%). Conclusion : In patients with PV who were resistant to or intolerant of HU, treatment with RUX was associated with greater and clinically meaningful improvements in PV-related symptom burden and QoL measures compared with BAT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Masszi:Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Durrant:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. He:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Côté:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Patient-Reported Quality of Life (QoL) in Elderly, Newly Diagnosed Multiple Myeloma (MM) Patients Receiving Bortezomib-Based Combinations: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1864-1864 ◽  
Author(s):  
Ruben Niesvizky ◽  
Ian W. Flinn ◽  
Robert Rifkin ◽  
Nashat Gabrail ◽  
Veena Charu ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Board Of Directors ◽  
Research Funding ◽  
Global Health Status ◽  
Linear Mixed Effect Model ◽  
Advisory Committees ◽  
Mixed Effect ◽  
Linear Mixed Effect ◽  
Patient Reported

Abstract Abstract 1864 Background: In addition to determining the efficacy and safety of different treatment options for MM, the impact of treatment and associated toxicities on patient-reported QoL should be evaluated. The US community-based phase 3b UPFRONT study compares the efficacy and safety of three bortezomib (VELCADE®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by weekly Vc maintenance, in elderly, newly diagnosed, transplant-ineligible MM patients. Updated efficacy and safety data are reported elsewhere at this meeting; here we present patient-reported QoL results – a secondary endpoint of the trial – from all 502 randomized patients, who received up to a maximum of 13 treatment cycles. Methods: Patients with symptomatic MM were randomized (1:1:1) to receive eight 21-day cycles of VcD (Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]), VcTD (Vc as before; T 100 mg/day, days 1–21; D as before), or VcMP (Vc as before; M 9 mg/m2, and P 60 mg/m2, days 1–4, every other cycle) induction, followed by five 35-day cycles of maintenance with Vc 1.6 mg/m2, days 1, 8, 15, 22. QoL was assessed using the EORTC QLQ-C30 questionnaire, which includes global health status, physical, role, cognitive, emotional, and social functioning, and symptom scales of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Global health status scores combine overall health and QoL scores, with higher scores reflecting better health status. Questionnaires were completed prior to dosing on day 1 of cycle 1 (baseline), prior to dosing on day 1 of every odd-numbered cycle, at the end-of-treatment visit, and every 12 weeks until progressive disease. Patient-reported QoL scores presented herein represent data collected within 1 year of randomization regardless of discontinuation status; for patients who died, missing assessments were assigned the worst possible score of 0. A linear mixed effect model was used to assess QoL changes over time, both within and between treatment arms. Sensitivity analyses were conducted to test the robustness of the primary analysis. Results: Patient baseline characteristics were well balanced across the VcD (n=168), VcTD (n=167), and VcMP (n=167) arms as reported previously (Niesvizky et al, EHA 2011). Median age was 74.5 (VcD), 73.0 (VcTD), and 72.0 (VcMP) years, and 71%, 62%, and 72% of patients had ISS stage II/III disease. QoL assessments were available at baseline and ≥1 post-baseline time point for 78% (VcD), 69% (VcTD), and 78% (VcMP) of patients. Observed data showed a downward trend in mean global health status score until cycle 7 (VcD, VcMP) or 9 (VcTD), followed by a trend to stabilizing/improving score thereafter (Figure). Symptom scores changed very little during induction in all arms, except for nausea/vomiting and diarrhea, with moderate improvements seen during maintenance. After fitting observed data with a linear mixed effect model, a significant decrease in mean global health status score from baseline to cycle 7 (induction period) was evident in all arms (VcD, p=0.0127; VcTD, p<0.0001; VcMP, p=0.0157), but there were no significant inter-arm differences. During cycles 9–13 (maintenance period), mean global health status scores remained decreased from baseline in the VcD and VcTD arms, and there were significant differences between VcTD and VcMP, with lower scores in the VcTD arm. Sensitivity analyses incorporating patients' QoL data collected after discontinuation of treatment (for patients who discontinued within 1 year) and utilizing a last observation carried forward approach, gave similar results to the linear mixed effect model. Conclusions: The observed data, linear mixed model estimates, and sensitivity analyses all show a common trend to a transient decrease in QoL during VcD, VcTD, and VcMP induction followed by a subsequent trend to improvement/stabilization in QoL during single-agent Vc maintenance. The trend to decreasing QoL seen during Vc-based induction may reflect the onset of treatment-related toxicities (particularly for VcTD, which was associated with somewhat higher toxicity rates). Post-induction improvements/stabilization in QoL may reflect the beneficial impact of achieving a response and the limited toxicity profile associated with weekly Vc maintenance. Disclosures: Niesvizky: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Onyx: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Charu:Pfizer: Equity Ownership; Bristol-Myers Squibb: Equity Ownership; Roche: Research Funding; GSK: Research Funding; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Huang:Millennium Pharmaceuticals, Inc: Employment. Choi:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment.

scholarly journals Correlation between MPN-SAF TSS and EORTC QLQ-C30 Scores in Patients with PV: Data from the Reveal Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2259-2259 ◽  
Author(s):  
Ivy Altomare ◽  
Aaron T. Gerds ◽  
David Lessen ◽  
Philomena Colucci ◽  
Shreekant Parasuraman ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Research Funding ◽  
Symptom Burden ◽  
Global Health Status ◽  
Employment Equity ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Introduction Polycythemia vera (PV) is characterized by clonal proliferation of myeloid cells and erythrocytosis. Patients with PV often present with symptoms or develop symptoms that may negatively impact quality of life (QOL). In clinical trials, the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) have both been used to assess symptom burden in patients with PV. This analysis was conducted in patients with PV enrolled in REVEAL, a multicenter, prospective, observational trial, in an attempt to corroborate previous work by Emanuel et al (J Clin Oncol 2012;30:4098), which demonstrated associations between the MPN-SAF TSS and EORTC QLQ-C30. Methods Patients ≥ 18 years of age with PV were enrolled and followed during usual care visits for ≤ 36 months. Patient-reported outcomes, including the MPN-SAF TSS and EORTC QLQ-C30, were collected at enrollment and at approximate 3-month intervals; only the forms completed at the time of enrollment were included in this analysis. MPN-SAF TSS items are scored on a linear analog scale ranging from 0 (absent) to 10 (worst imaginable), and individual symptom scores were added together to calculate a TSS; higher scores represent worse symptom burden. In the EORTC QLQ-C30, 28 questions are scored using a 4-point scale indicating frequency: 1 (not at all), 2 (a little bit), 3 (quite a bit), and 4 (very much); this includes 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Two questions on overall health and QOL are rated on a 1 (very poor) to 7 (excellent) scale. Five multi-item functional scales (physical, role, cognitive, emotional, and social), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), and a multi-item global health status/QOL scale are derived from the 30 questions. Linear transformation to 0-100 was applied to raw scores to obtain scores for each scale or single item. Higher scores for functional scales and global health status represent higher functioning and better health status/QOL, respectively. Higher scores for symptom scales/items represent higher symptom burden. Pearson correlation coefficient was used to assess correlations between MPN-SAF TSS and EORTC QLQ-C30 scales. Results As of data cutoff (April 30, 2018), 2,298 of 2,510 enrolled patients (91.6%) had completed both MPN-SAF TSS and EORTC QLQ-C30 forms at enrollment. Median age was 67 years (range, 22-97 years), 54.0% were male, and 89.7% were Caucasian. Median disease duration at the time of enrollment was 4.1 years. The majority (52.5%) of patients were treated with hydroxyurea (28.7%) or hydroxyurea with phlebotomy (23.8%). The mean MPN-SAF TSS was 18.7 (out of 100) compared to 21.8 reported by Emanuel et al 2012. The 4 symptoms with the highest mean scores were fatigue (3.5), early satiety (2.6), inactivity (2.5), and itching (2.3). The QLQ-C30 mean scores for overall QOL and health were 5.5 and 5.3, respectively. EORTC QLQ-C30 symptom scales were highest for fatigue (29.9), insomnia (28.7), and pain (20.0). Correlation between MPN-SAF TSS and EORTC QLQ-C30 results showed stronger associations between multiple items (Table). Calculated TSS had the strongest association with fatigue (r = 0.72), pain (r = 0.59), cognitive functioning (r = -0.58), and emotional functioning (r = -0.58). Problems with concentration in the MPN-SAF TSS was moderately correlated with cognitive functioning (r = -0.70) in the EORTC QLC-C30. Fatigue assessments were also moderately correlated (r = 0.65) between the MPN-SAF TSS and EORTC QLQ-C30. Conclusions In this analysis of prospectively gathered real-world data, the MPN-SAF TSS results confirm that patients with PV experience a recognizable constellation of symptoms, including fatigue, early satiety, inactivity, and itching. Not surprisingly, PV-related symptoms have a negative impact on QOL. There were moderate correlations (r = 0.5-0.75) between the MPN-SAF TSS and the EORTC QLC-C30 with respect to global health status/QOL, the 5 functional scales, and fatigue, pain, and dyspnea. Consistent with the previous analysis, this analysis provides further evidence that the MPN-SAF TSS represents an accurate, yet simple tool to assess PV-related symptoms and their potential impact on QOL. Disclosures Altomare: Novartis: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Celgene: Other: Advisory Board Member; Ipsen: Other: Advisory Board Member. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Lessen:Abbvie: Honoraria; Teva: Honoraria, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Astellas: Research Funding; Bayer: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Portola: Honoraria, Speakers Bureau; Janssen: Research Funding. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Mesa:Pfizer: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding; Novartis: Consultancy; UT Health San Antonio - Mays Cancer Center: Employment; CTI Biopharma: Research Funding; Genentech: Research Funding.

The Effects of Azacitidine On Quality of Life: A Prospective Longitudinal Assessment

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4938-4938
Author(s):  
Eric Tseng ◽  
Richard A. Wells ◽  
Shabbir MH Alibhai ◽  
Adam Lam ◽  
Alex Mamedov ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Global Health Status ◽  
Advisory Committees ◽  
Over Time

Abstract Abstract 4938 The effect of azacitidine (AZA) on health related quality of life (QOL) compared with best supportive care in MDS patients has been evaluated by Kornblith A. et al (JCO 2002) in a prospective randomized CALGB trial. The study demonstrated improved fatigue, dyspnea, physical functioning and psychological state in patients receiving AZA. One limitation is the relatively short follow up (last QOL measured at 8. 6 months) and the lack of validation in a non-trial setting. We have been conducting prospective assessments of QOL in all patients registered at our MDS clinic using the instruments EORTC QLQ-C30, FACT-Fatigue, EQ-5D and a global fatigue scale. We present longitudinal data on 56 registered patients registered in our program who were treated with AZA, 50 with serial QOLs. Methods: We examined and compared QOL scores at AZA start (baseline) and over time in all patients. We considered the following co-variates' potential impact on QOL scores: age, sex, IPSS, time from diagnosis, being a responder, # cycles and transfusion dependence. We used univariate linear regression analysis for continuous variables and analysis of variance (ANOVA) for categorical variables to determine their relationship with QOL scores at baseline and over time. For time-dependent covariates, linear mixed model was performed with random intercept and unstructured covariance matrix. Clinically significant (CS) score differences were considered 10 points for the QLQ-C30, 4 for the FACT-Fatigue and 0. 08 for the EQ-5D (7 for the visual analog score). The impact of baseline covariates on the QOL scores for global health, fatigue and dyspnea were determined by backward selection procedure of regression analysis using the Bonferroni adjusted P value of <0. 01 for multiple comparisons. Patients provided informed consent for this REB approved study. Results: 56 MDS patients consented to our registry have been treated with AZA between Oct 2008 and July 2012. The median age was 72, 60% were male and 77% had int-2/high risk IPSS MDS. 64 % were transfusion dependent (TD) at baseline. With a median time to death or last follow up of 16 months (range 1. 5–45) a median of 11 cycles of AZA were administered with 34% remaining on drug for a median of 25 cycles (IQR 8–32). The overall response rate (ORR) was 62%: 25% CR; 5% MCR; 4% PR; 28% HI. Stable disease (SD) was seen in 26% and not considered a response. 53% became transfusion independent (TI). 59% have died and 61% developed leukemia or progressed to > 30% blasts at a median time of 13 months. Overall survival was 18 months (95% CI 14. 5–26). 50 were evaluable for HrQOL with a median time between each serial QOL of 13 weeks (IQR 10–18). QOL was assessed at baseline (within 12 weeks pre-AZA start) in 50 patients, 2x in 44, 3x in 32, 4x in 22 and 5x in 14 patients (exceeding 52 weeks follow up). Looking at all 50 patients, overall, function and symptom domains remained stable over time in all instruments. At baseline, there were no statistically significant differences in QOL scores between responders and non responders. Nevertheless, clinically important differences were seen in physical, role, cognitive and social functioning, global health status (all higher in responders). Assessing QOL changes over time and considering baseline and time-dependent predictive factors in multivariate analysis, responders had significantly superior global health status (p=. 001) and EQ-5D scores (p=. 0002) and lower levels of fatigue (p<. 0001). If transfusion dependence status at time of QOL was included in the model, this often supplanted response as predictive of higher scores over time, likely representing the strong relationship between response and transfusion dependence. Conclusions: In addition to validating the clinical outcomes of AZA-001 study, we validate the importance of clinical response on QOL in MDS patients treated with AZA. Unlike the CALGB study, we observed relative stability in global health status and fatigue scores in responding patients and overall declines in non-responding patients. The higher scores at baseline in the patients destined for response raises the intriguing possibility that QOL at AZA start may be independently predictive of response perhaps because of improved tolerability and ability to remain on drug for the requisite number of cycles to achieve response. Disclosures: Wells: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: 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. Buckstein:Celgene: 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.

scholarly journals Impact of Modified Thalidomide Dosing in Bortezomib/Thalidomide/Dexamethasone for Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant-Eligible: A Matching-Adjusted Indirect Comparison

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4739-4739
Author(s):  
Pieter Sonneveld ◽  
Maria-Victoria Mateos ◽  
Adrián Alegre ◽  
Thierry Facon ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Board Of Directors ◽  
Research Funding ◽  
Indirect Comparison ◽  
Employment Equity ◽  
Advisory Committees ◽  
Post Transplant ◽  
Post Induction ◽  
Adjusted Indirect Comparison ◽  
Equity Ownership

Introduction: For patients with newly diagnosed multiple myeloma (NDMM) who are transplant-eligible, bortezomib/thalidomide/dexamethasone (VTd) is a standard of care (SoC) for induction and consolidation therapy. Clinical practice has evolved to use a modified VTd dose (VTd-mod; 100 mg thalidomide daily), which is reflected in recent treatment guidelines. As VTd-mod has become a real-world SoC, a matching-adjusted indirect comparison (MAIC) of the VTd-mod dose from recent clinical trials versus the dose included in the label (VTd-label; ramp up to 200 mg thalidomide daily) was performed to understand the effect on efficacy of modified VTd dosing for patients with NDMM who are transplant-eligible. Methods: For each outcome (overall survival [OS], progression-free survival [PFS], overall response rates [ORR] post-induction and post-transplant, and rate of peripheral neuropathy), a naïve comparison and a MAIC were performed. Data for VTd-label were obtained from the phase 3 PETHEMA/GEM study (Rosiñol L, et al. Blood. 2012;120[8]:1589-1596). Data for VTd-mod were pooled from the phase 3 CASSIOPEIA study (Moreau P, et al. Lancet. 2019;394[10192]:29-38) and the phase 2 NCT00531453 study (Ludwig H, et al. J Clin Oncol. 2013;31[2]:247-255). Patient-level data for PETHEMA/GEM and CASSIOPEIA were used to generate outcomes of interest and were validated against their respective clinical study reports; aggregate data for NCT00531453 were extracted from the primary publication. Matched baseline characteristics were age, sex, ECOG performance status, myeloma type, International Staging System (ISS) stage, baseline creatinine clearance, hemoglobin level, and platelet count. Results: Patients received VTd-mod (n = 591) or VTd-label (n = 130). After matching, baseline characteristics were similar across groups. For OS, the naïve comparison and the MAIC showed that VTd-mod was non-inferior to VTd-label (MAIC HR, 0.640 [95% CI: 0.363-1.129], P = 0.121; Figure 1A). VTd-mod significantly improved PFS versus VTd-label in the naïve comparison and MAIC (MAIC HR, 0.672 [95% CI: 0.467-0.966], P = 0.031; Figure 1B). Post-induction ORR was non-inferior for VTd-mod versus VTd-label (MAIC odds ratio, 1.781 [95% CI: 1.004-3.16], P = 0.065). Post-transplant, VTd-mod demonstrated superior ORR in both the naïve comparison and MAIC (MAIC odds ratio, 2.661 [95% CI: 1.579-4.484], P = 0.001). For rates of grade 3 or 4 peripheral neuropathy, the naïve comparison and MAIC both demonstrated that VTd-mod was non-inferior to VTd-label (MAIC rate difference, 2.4 [⁻1.7-6.49], P = 0.409). Conclusions: As naïve, indirect comparisons are prone to bias due to patient heterogeneity between studies, a MAIC can provide useful insights for clinicians and reimbursement decision-makers regarding the relative efficacy and safety of different treatments. In this MAIC, non-inferiority of VTd-mod versus VTd-label was demonstrated for OS, post-induction ORR, and peripheral neuropathy. This analysis also showed that VTd-mod significantly improved PFS and ORR post-transplant compared with VTd-label for patients with NDMM who are transplant-eligible. A limitation of this analysis is that unreported or unobserved confounding factors could not be adjusted for. Disclosures Sonneveld: Takeda: Honoraria, Research Funding; SkylineDx: Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding. Mateos:Janssen, Celgene, Takeda, Amgen, Adaptive: Honoraria; AbbVie Inc, Amgen Inc, Celgene Corporation, Genentech, GlaxoSmithKline, Janssen Biotech Inc, Mundipharma EDO, PharmaMar, Roche Laboratories Inc, Takeda Oncology: Other: Advisory Committee; Janssen, Celgene, Takeda, Amgen, GSK, Abbvie, EDO, Pharmar: Membership on an entity's Board of Directors or advisory committees; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Takeda Oncology.: Speakers Bureau; Amgen Inc, Janssen Biotech Inc: Other: Data and Monitoring Committee. Alegre:Celgene, Amgen, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees. Facon:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: 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. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria. Hashim:Ingress-Health: Employment. Vincken:Janssen: Employment, Equity Ownership. Kampfenkel:Janssen: Employment, Equity Ownership. Cote:Janssen: Employment, Equity Ownership. Moreau:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.

scholarly journals A Phase I Trial of Janus Kinase (JAK) Inhibition with INCB039110 in Acute Graft-Versus-Host Disease (aGVHD)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 390-390 ◽  
Author(s):  
Mark A. Schroeder ◽  
H. Jean Khoury ◽  
Madan Jagasia ◽  
Haris Ali ◽  
Gary J. Schiller ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Janus Kinase ◽  
Cell Transplant ◽  
Employment Equity ◽  
Advisory Committees ◽  
Daily Dose ◽  
Equity Ownership ◽  
Grade 3 ◽  
Steroid Refractory

Abstract Background: Corticosteroids are considered standard first-line systemic therapy for patients with aGVHD, but this approach is effective in only approximately half of all cases. For patients who progress or do not respond to corticosteroids, no specific agent has been identified as standard, and regimens are typically selected based on investigator experience and patient co-morbidities. In preclinical models, JAK inhibition has been shown to impair production of cytokines as well as the differentiation and trafficking of T cells implicated in the pathogenesis of aGVHD. Retrospective studies have suggested that JAK1/JAK2 inhibition with ruxolitinib treatment provides clinical benefit in patients with steroid-refractory GVHD (Zeiser et al, Leukemia 2015;29:2062-2068). Herein, we report preliminary safety results from a prospective randomized, parallel-cohort, open-label phase 1 trial evaluating the potent and selective JAK 1 inhibitor INCB039110 in patients with aGVHD. Methods: Male or female patients 18 years or older who underwent their first allo-hematopoietic stem cell transplant (HSCT) from any donor source and developed grades IIB-IVD aGVHD were eligible for the study. Patients were randomized 1:1 to either a 200 or 300 mg oral daily dose of INCB039110 in combination with corticosteroids, and were stratified based on prior treatment status (treatment-naive [TN] versus steroid-refractory [SR]). The primary endpoint of the study was safety and tolerability; secondary endpoints included overall response rate at Days 14, 28, 56, and 100, non-relapse mortality, and pharmacokinetic (PK) evaluations. Patients were assessed through Day 28 for dose-limiting toxicities (DLTs) and response. A Bayesian approach was used for continuous monitoring of DLTs from Days 1-28. Treatment continued until GVHD progression, unacceptable toxicity, or withdrawal from the study. Acute GVHD was graded according to MN-CIBMTR criteria; adverse events (AEs) were graded according to NCICTCAE v 4.03. Results: Between January and June 2016, 31 patients (TN, n=14; SR, n= 17) were randomized. As of July 25, 2016, data were available from 30 patients who received an oral daily dose of 200 mg (n=14) or 300 mg (n=16) INCB039110 in combination with 2 mg/kg methylprednisolone (or equivalent dose of prednisone). The median durations of treatment were 60.8 days and 56.5 days for patients receiving a daily dose of 200 mg and 300 mg INCB039110, respectively. One DLT of Grade 3 thrombocytopenia was reported. The most frequently reported AEs included thrombocytopenia/platelet count decrease (26.7%), diarrhea (23.3%), peripheral edema (20%), fatigue (16.7%), and hyperglycemia (16.7%). Grade 3 or 4 AEs occurred in 77% of patients and with similar frequency across dose groups and included cytomegalovirus infections (n=3), gastrointestinal hemorrhage (n=3), and sepsis (n=3). Five patients had AEs leading to a fatal outcome, including multi-organ failure (n=2), sepsis (n=1), disease progression (n=1), and bibasilar atelectasis, cardiopulmonary arrest, and respiratory distress (n=1); none of the fatal events was attributed to INCB039110. Efficacy and PK evaluations are ongoing and will be updated at the time of presentation. Conclusion: The oral, selective JAK1 inhibitor INCB039110 can be given safely to steroid-naive or steroid-refractory aGVHD patients. The safety profile was generally consistent in both dose groups. Biomarker evaluation, PK, and cellular phenotyping studies are ongoing. The recommended phase 2 dose will be selected and reported based on PK studies and final safety data. Disclosures Schroeder: Incyte Corporation: Honoraria, Research Funding. Khoury:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jagasia:Incyte Corporation: Research Funding; Therakos: Research Funding; Janssen: Research Funding. Ali:Incyte Corporation: Research Funding. Schiller:Incyte Corporation: Research Funding. Arbushites:Incyte Corporation: Employment, Equity Ownership. Delaite:Incyte Corporation: Employment, Equity Ownership. Yan:Incyte Corporation: Employment, Equity Ownership. Rhein:Incyte Corporation: Employment, Equity Ownership. Perales:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chen:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. DiPersio:Incyte Corporation: Research Funding.

scholarly journals Role of Remission Status and Prior Transplant in Optimizing Survival Outcomes Following Allogeneic Hematopoietic Stem Transplantation (HSCT) in Patients Who Received Inotuzumab Ozogamicin (INO) for Relapsed / Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 886-886
Author(s):  
Partow Kebriaei ◽  
Matthias Stelljes ◽  
Daniel J. DeAngelo ◽  
Nicola Goekbuget ◽  
Hagop M. Kantarjian ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Survival Probability ◽  
Research Funding ◽  
Employment Equity ◽  
Inotuzumab Ozogamicin ◽  
Advisory Committees ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Equity Ownership

Abstract Introduction: Attaining complete remission (CR) prior to HSCT is associated with better outcomes post-HSCT. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, has shown significantly higher remission rates (CR/CRi and MRD negativity) compared with standard chemotherapy (SC) in patients (pts) with R/R ALL (Kantarjian et al. N Engl J Med. 2016). Pts treated with INO were more likely to proceed to HSCT than SC, which allowed for a higher 2-yr probability of overall survival (OS) than patients receiving SC (39% vs 29%). We investigated the role of prior transplant and proceeding directly to HSCT after attaining remission from INO administration as potential factors in determining post-HSCT survival to inform when best to use INO in R/R ALL patients. Methods: The analysis population consisted of R/R ALL pts who were enrolled and treated with INO and proceeded to allogeneic HSCT as part of two clinical trials: Study 1010 is a Phase 1/2 trial (NCT01363297), while Study 1022 is the pivotal randomized Phase 3 (NCT01564784) trial. Full details of methods for both studies have been previously published (DeAngelo et al. Blood Adv. 2017). All reference to OS pertains to post-HSCT survival defined as time from HSCT to death from any cause. Results: As of March 2016, out of 236 pts administered INO in the two studies (Study 1010, n=72; Study 1022, n=164), 101 (43%) proceeded to allogeneic HSCT and were included in this analysis. Median age was 37 y (range 20-71) with 55% males. The majority of pts received INO as first salvage treatment (62%) and 85% had no prior SCT. Most pts received matched HSCTs (related = 25%; unrelated = 45%) with peripheral blood as the predominant cell source (62%). The conditioning regimens were mainly myeloablative regimens (60%) and predominantly TBI-based (62%). Dual alkylators were used in 13% of pts, while thiotepa was used in 8%. The Figure shows post-transplant survival in the different INO populations: The median OS post-HSCT for all pts (n=101) who received INO and proceeded to HSCT was 9.2 mos with a 2-yr survival probability of 41% (95% confidence interval [CI] 31-51%). In patients with first HSCT (n=86) the median OS post-HSCT was 11.8 mos with a 2-yr survival probability of 46% (95% CI 35-56%). Of note, some patients lost CR while waiting for HSCT and had to receive additional treatments before proceeding to HSCT (n=28). Those pts who went directly to first HSCT after attaining remission with no intervening additional treatment (n=73) fared best, with median OS post-HSCT not reached with a 2-yr survival probability of 51% (95% CI 39-62%). In the latter group, 59/73 (80%) attained MRD negativity, and 49/73 (67%) were in first salvage therapy. Of note, the post-HSCT 100-day survival probability was similar among the 3 groups, as shown in the Table. Multivariate analyses using Cox regression modelling confirmed that MRD negativity during INO treatment and no prior HSCT were associated with lower risk of mortality post-HSCT. Other prognostic factors associated with worse OS included older age, higher baseline LDH, higher last bilirubin measurement prior to HSCT, and use of thiotepa. Veno-occlusive disease post-transplant was noted in 19 of the 101 pts who received INO. Conclusion: Administration of INO in R/R ALL pts followed with allogeneic HSCT provided the best long-term survival benefit among those who went directly to HSCT after attaining remission and had no prior HSCT. Disclosures DeAngelo: Glycomimetics: Research Funding; Incyte: Consultancy, Honoraria; Blueprint Medicines: Honoraria, Research Funding; Takeda Pharmaceuticals U.S.A., Inc.: Honoraria; Shire: Honoraria; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding; BMS: Consultancy; ARIAD: Consultancy, Research Funding; Immunogen: Honoraria, Research Funding; Celgene: Research Funding; Amgen: Consultancy, Research Funding. Kantarjian: Novartis: Research Funding; Amgen: Research Funding; Delta-Fly Pharma: Research Funding; Bristol-Meyers Squibb: Research Funding; Pfizer: Research Funding; ARIAD: Research Funding. Advani: Takeda/ Millenium: Research Funding; Pfizer: Consultancy. Merchant: Pfizer: Consultancy, Research Funding. Stock: Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang: Pfizer: Employment, Equity Ownership. Zhang: Pfizer: Employment, Equity Ownership. Loberiza: Pfizer: Employment, Equity Ownership. Vandendries: Pfizer: Employment, Equity Ownership. Marks: Pfizer: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau.

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