scholarly journals Quality of Life, Psychological Distress, and Prognostic Awareness in Caregivers of Patients with Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3044-3044
Author(s):  
Elizabeth K. O'Donnell ◽  
Yael Shapiro ◽  
Omar Nadeem ◽  
Andrew J. Yee ◽  
Jacob P. Laubach ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Board Of Directors ◽  
Research Funding ◽  
Ptsd Symptoms ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Significant Depression ◽  
Clinically Significant

Abstract Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Although caregivers of MM patients play a critical role in supporting their loved ones throughout the illness course, studies examining caregiver quality of life (QOL), psychological distress, and prognostic awareness are lacking. Methods: We conducted a cross-sectional, multisite study of patients undergoing treatment with MM (excluding maintenance therapy) and their caregivers between 6/2020-3/2021. Eligible caregivers were identified by the patient as the primary caregiver and enrolled to 1 of 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2-3 lines; 3) ≥4 lines of therapy. Caregivers completed validated questionnaires to assess their QOL, psychological distress, and perceptions of prognosis. Patients also completed validated questions to assess their perception of prognosis. We used descriptive statistics to describe caregiver QOL, psychological distress, and perception of prognosis. We then descriptively compared psychological distress and perception of prognosis between patient and caregiver dyads. Results: We enrolled 127 caregivers of MM patients (newly diagnosed (n=43), 2-3 (n=40), and ≥ 4 lines of therapy (n=44)). Median caregiver age was 61.8 years (range 24.0-81.9); 71.7% (91/127) were female; and 68.5% (87/127) were taking care of their spouse/partner. Caregiver QOL and psychological distress did not differ by lines of therapy. The rate of clinically significant depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms were 15.8% (20/127), 44.1% (56/127), and 24.4% (31/127), respectively. When examining dyads, caregivers reported higher rates of clinically significant anxiety symptoms (44.4% vs. 22.5%) compared to MM patients. Caregivers reported less clinically significant depression symptoms (15.3% vs. 24.2%) and similar rates of clinically significant PTSD symptoms (24.2% vs 25.0%). Overall, 89.6% (112/125) of caregivers reported that it is 'extremely' or 'very' important to know about the patient's prognosis and 55.6% (70/126) stated that they had received adequate information regarding the patient's prognosis. Caregivers reported that prognostic information was 'extremely' or 'very' helpful in making decisions about treatment (94.0%, 109/116), preparing for the future (88.6%, 101/114), and coping with the disease (85.2%, 98/115). Most caregivers (84.2%, 101/120), reported that the oncologist had told them the patient's cancer was incurable. In contrast, only 53.6% (59/110) of caregivers reported that they thought the patient's cancer was incurable and 37.9% (58/114) acknowledged that the patient is terminally ill. Caregiver demographics, line of therapy, QOL, and psychological distress were not associated with their perceptions of the patient's prognosis. When examined in dyads, caregivers were more likely to report that the patient is terminally ill (50.1% vs. 30.1%). There was no difference in caregivers' and patients' report that the oncologist said MM is incurable (83.3% vs. 84.2%). Conclusions: Caregivers of patients undergoing treatment for MM experience substantial psychological distress across the disease continuum, particularly anxiety. Supportive care interventions are needed to improve caregivers' QOL and to reduce their psychological distress. Although the majority of caregivers of MM patients report that knowing the patient's prognosis is extremely important and report that the oncologist told them that the patient was incurable, a significant portion of caregivers report that the patient is curable. Interventions are needed to promote effective coping and to enhance caregiver's perception of the patient's prognosis to facilitate informed-decision making. Disclosures O'Donnell: Janssen: Consultancy; Takeda: Consultancy; Oncopeptide: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Bristol Myer Squibb: Consultancy. Nadeem: Takeda: Consultancy; Bristol Myer Squibb: Consultancy; GSK: Consultancy; Karyopharm: Consultancy; Adaptive: Consultancy. Yee: Karyopharm: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Bristol Myers Squibb: Consultancy; Amgen: Consultancy. Branagan: Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy; CSL Behring: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mo: Janssen: Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Eli Lilly: Consultancy. Munshi: Celgene: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Abbvie: Consultancy; Legend: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Sperling: Adaptive: Consultancy. Richardson: AstraZeneca: Consultancy; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; Karyopharm: Consultancy, Research Funding; Secura Bio: Consultancy; Sanofi: Consultancy; Regeneron: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other.

scholarly journals Psychological Distress in Young Adults with Acute Myeloid Leukemia Undergoing Induction Chemotherapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Bethany Lockwood ◽  
Areej El-Jawahri ◽  
Alison R. Walker ◽  
Deborah Russell ◽  
Jillian Gustin ◽  
...  
Keyword(s):  
Older Adults ◽  
Psychological Distress ◽  
Board Of Directors ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Symptom Burden ◽  
Ptsd Symptoms ◽  
Advisory Committees ◽  
Clinically Significant

Introduction: Young adults (YAs), ages 18-39 years diagnosed with cancer have distinct physical, developmental, and psychosocial needs that are often unmet during oncologic treatment. In acute myeloid leukemia (AML), a disease affecting both younger and older adults, patients navigate several treatment intensity choices, and with intensive induction chemotherapy are often balancing a chance of cure with a risk of death. Furthermore, YAs with AML can have marked life disruptions with this unpredictable illness trajectory and prolonged induction hospitalization, further conflicting with normal development at this stage. Fundamentally different than solid tumors, we lack an understanding of the YA experience in AML induction compared to their older counterparts. This study explores patient-reported outcomes (PROs) including quality of life (QOL) and physical and psychological symptom burden among YAs undergoing induction chemotherapy. Methods: We conducted a secondary analysis of 160 patients with high-risk AML hospitalized to receive intensive chemotherapy who were enrolled in a randomized control trial of palliative care (PC) intervention versus standard oncology care. Patients with newly diagnosed, relapsed, or refractory AML receiving intensive treatment requiring a 4-6 week hospitalization were enrolled in the study. We used the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), the Edmonton Symptom Assessment System (ESAS), the Hospital Anxiety and Depression Scale (HADS), and the Post-Traumatic Stress Disorder (PTSD) Checklist to assess QOL, symptom burden, and psychological distress respectively. Assessments were administered at baseline, week-2, and week-4 following initiation of chemotherapy. We used descriptive statistics to compare PROs at baseline between YAs (< 40 years) and older adults. We used linear regression models controlling for PC intervention effect when examining the association between age (YAs versus older adults) and PROs at week-2. We used linear mixed effect models controlling for randomization to the PC intervention to assess the association between age and PROs longitudinally throughout the hospitalization. Results: Of the 160 patients with high-risk AML enrolled in this study, 14 (8.8%) were YAs < 40 years. Demographic characteristics highlight that the majority of YAs had relapsed AML (n=10, 71.4%) and there was a greater presence of racial and ethnic diversity compared to older adults. The baseline mean QOL score for YAs was 110.5 (SD 34.2). Overall, 57.1% (8/14) reported clinically significant anxiety and 50% (7/14) reported clinically significant PTSD symptoms at baseline. Fewer YA patients, 21.4% (3/14) reported clinically significant depression. Evaluation of PROs at week-2 nadir adjusted for randomization to the PC intervention, highlighted a significant lower QOL (β=-18.27; p=0.036), higher anxiety (β=2.72; p=0.048), and higher PTSD symptoms (β=10.34; p=0.007) for YAs compared to older adults. Longitudinal analyses exploring the impact of age on PROs across induction hospitalization demonstrated that YAs had consistently significant higher anxiety (β=3.66; p=0.024) and PTSD symptoms (β=15.64; p<0.001) compared to older adults [Figure 1]. Conclusions: For YAs with AML undergoing induction chemotherapy, anxiety and PTSD symptoms are highly prevalent both at baseline and longitudinally throughout the induction hospitalization. This demonstrates a continued unmet need of the significant psychological distress and intensified hospitalization experience for YAs compared to their older counterparts. Given that distress during induction hospitalization can be predictive of post-treatment outcomes, it is imperative to tailor integrated supportive care and psychosocial interventions for YAs with AML during induction chemotherapy. Disclosures Walker: Geron: Research Funding; Newave Pharmaceuticals: Research Funding. Bhatnagar:KaryoPharm Therapuetics: Research Funding; Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Quality of Life, Psychological Distress, and Prognostic Awareness in Patients with Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4082-4082
Author(s):  
Elizabeth K. O'Donnell ◽  
Yael Shapiro ◽  
Omar Nadeem ◽  
Andrew J. Yee ◽  
Jacob P. Laubach ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Board Of Directors ◽  
Research Funding ◽  
Terminal Illness ◽  
Symptom Burden ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Line Of Therapy ◽  
Patient’S Perception

Abstract Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and prognostic awareness by line of therapy are lacking. Methods: We conducted a cross-sectional, multi-site study of patients undergoing treatment for MM (excluding maintenance therapy) between 6/2020-1/2021. To capture the full spectrum of treatment, we conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2-3 lines; and 3) ≥ 4 lines. Patients completed validated questionnaires to assess their QOL, symptom burden, fatigue, psychological distress, and perceptions of prognosis. We used multivariate linear regression models to examine the association between lines of therapy, QOL, psychological distress, with patient's perception of their prognosis. Results: We enrolled 180 patients with MM (newly diagnosed (n=60), 2-3 lines (n=60), and ≥4 lines of therapy (n=60)). QOL and fatigue scores did not differ by lines of therapy: (QOL: 116.6 (SD=20.6) vs. 112.3 (SD=28.2) vs. 110.6 (SD=29.6); Fatigue: 36.9 (SD=9.9) vs. 35.4 (SD=11.9) vs. 33.7 (SD=12.5). There were also no statistically significant differences in depression, anxiety, or PTSD symptoms by line of therapy. The rate of clinically significant depression, anxiety, and PTSD symptoms were 23.9% (43/180), 23.9% (43/180), and 24.4% (44/180), respectively. Overall, 84% (147/175) of patients reported that it is 'extremely' or 'very' important to know about their prognosis, and the majority (66.1%, 117/177) stated that they had received adequate information regarding their prognosis. Patients reported that prognostic information was 'extremely' or 'very' helpful in making decisions about treatment (93.4%, 155/166), coping with the disease (87.4%, 145/166), and preparing for the future (86.8%, 144/166). Most patients, 84.7% (149/176) reported that their oncologist told them their cancer was incurable but only 30.6% (53/173) acknowledged that they were terminally ill and only 42.0% (73/174) reported that they thought their cancer was incurable . Patients receiving 2-3 lines of therapy were more likely to acknowledge their terminal illness (36.7% vs. 19.6%, p=0.045) and that their MM was incurable (90.0% vs. 75.9%, p=0.047) compared to those receiving 1 st line therapy. QOL and psychological distress were not associated with patient's perception that their MM was incurable. However, patients who acknowledged their terminal illness reported higher depression (B=1.52, P = 0.009), anxiety (B=1.52, P=0.0037), symptom burden (B=7.42, P=0.007), and lower QOL (B=-14.78, p=0.001). Conclusions: MM patients undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, irrespective of their line of therapy. Although the majority reported that their oncologist had told them that their cancer is incurable, a substantial proportion still reported that they believed they were curable. Acknowledgement of terminal illness was associated with higher rates of psychological distress and symptoms burden and lower QOL. Interventions are needed to improve patients' QOL, reduce their psychological distress, and cultivate adaptive coping strategies that may help improve the patient experience over the MM disease course. Disclosures O'Donnell: Adaptive: Consultancy; Oncopeptide: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Karyopharm: Consultancy. Nadeem: Bristol Myer Squibb: Consultancy; GSK: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy. Yee: Adaptive: Consultancy; Bristol Myers Squibb: Consultancy; GSK: Consultancy; Oncopeptides: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Janssen: Consultancy. Branagan: Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy; CSL Behring: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson: Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mo: Epizyme: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Eli Lilly: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Munshi: Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Legend: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Adaptive Biotechnology: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Sperling: Adaptive: Consultancy. Richardson: AbbVie: Consultancy; Takeda: Consultancy, Research Funding; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; AstraZeneca: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; Regeneron: Consultancy; Secura Bio: Consultancy; Celgene/BMS: Consultancy, Research Funding; Sanofi: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other.

scholarly journals Quality of Life and Psychological Distress in Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2291-2291
Author(s):  
Areej El-Jawahri ◽  
Lauren Waldman ◽  
Joseph Greer ◽  
Gregory A. Abel ◽  
David P. Steensma ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Psychological Distress ◽  
Older Patients ◽  
Research Funding ◽  
Tertiary Care ◽  
Intensive Chemotherapy ◽  
Significant Depression ◽  
Linear Effects ◽  
Clinically Significant

Abstract Background: Older patients with AML face difficult treatment decisions as they can be treated either with multi-drug 'intensive' chemotherapy requiring a prolonged hospitalization, or 'non-intensive' chemotherapy. Although intensive chemotherapy is often perceived by clinicians as more burdensome, studies comparing patients' quality of life (QOL) and psychological distress while receiving these treatments are lacking. Methods: We conducted a longitudinal study of older patients (≥ 60 years) newly diagnosed with AML receiving intensive (i.e. 7+3: cytarabine/anthracycline combination) or non-intensive (i.e. hypomethylating agents) chemotherapy at two tertiary care hospitals. We assessed patient's QOL [Functional Assessment of Cancer Therapy-Leukemia], and psychological distress [Hospital Anxiety and Depression Scale [HADS]] at baseline and 2, 4, 8, 12, and 24 weeks after diagnosis. We compared the proportion of patients in each group reporting clinically significant depression or anxiety (HADS subscale cut off ≥ 7) and used mixed linear effects models to compare QOL and psychological distress longitudinally between groups. Results: We enrolled consecutive patients within 72 hours of initiating intensive (n=50) or non-intensive (n=50) chemotherapy. There were no differences in baseline QOL, depression, or anxiety symptoms between the groups. At baseline, 33.33% (33/100) and 30% (30/100) of the overall cohort reported clinically significant depression and anxiety, respectively, with no differences between groups. At 4 weeks, 41.98% (34/81) of patients in the overall cohort reported clinically significant depression, with no differences between groups. In mixed linear effects models, there were no differences in QOL (β=-0.71, SE=1.12, P=0.527), depression (β=0.24, SE=0.20, P=0.226), or anxiety (β=-0.16, SE=0.19, P=0.386) symptoms between groups over time. Conclusion: Older patients with AML receiving intensive and non-intensive chemotherapy experience similar QOL impairments and high rates of psychological distress. These findings underscore the need to develop supportive care interventions for older patients with AML, regardless of their initial treatment strategy. Disclosures Brunner: Takeda: Research Funding; Novartis: Research Funding; Celgene: Consultancy, Research Funding. Fathi:Celgene: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Boston Biomedical: Consultancy, Honoraria; Astellas: Honoraria; Agios: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. DeAngelo:ARIAD: Consultancy, Research Funding; Takeda: Honoraria; Amgen: Consultancy; Shire: Honoraria; Blueprint Medicines: Honoraria, Research Funding; Pfizer Inc: Consultancy, Honoraria; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; BMS: Consultancy; Glycomimetics: Research Funding; Incyte: Consultancy, Honoraria. Amrein:Takeda: Research Funding.

scholarly journals Comparison of Denosumab Versus Intravenous (IV) Bisphosphonate Use for Hypercalcemia in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-16
Author(s):  
Matthew M Lei ◽  
Erica Tavares ◽  
Uvette Lou ◽  
Evan Buzgo ◽  
Noopur S. Raje ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Dysfunction ◽  
Board Of Directors ◽  
Research Funding ◽  
Additional Dose ◽  
Newly Diagnosed ◽  
Median Dose ◽  
Publicly Traded ◽  
Advisory Committees ◽  
The Past

Background Hypercalcemia (HC) is a frequent complication of multiple myeloma (MM) occurring in 20-30% of patients. This is often associated with renal dysfunction and both features are important myeloma defining events resulting in significant morbidity and mortality. Denosumab, a fully human monoclonal antibody that inhibits RANKL, has been evaluated in the prevention of skeletal related events in patients with newly diagnosed MM, as well as the treatment of bisphosphonate-refractory HC of malignancy (HCM). Cases of denosumab for HCM in MM patients with renal dysfunction have been described. Both denosumab and IV bisphosphonates (IVB) represent treatment options for HC in MM. We describe a comparison of patients with MM with HC who received denosumab vs IVBs. Methods We retrospectively identified patients age ≥18 with a diagnosis of MM with HC (corrected serum calcium level [CSC] >10.5 mg/dL). Patients were included if they received either denosumab or IVB (zoledronic acid [ZA] or pamidronate), between April 2016 and June 2020. The primary endpoint was complete response (CR), defined as normalization of CSC to less than 10.5 mg/dL. Secondary endpoints included HC relapse (CSC >10.5 mg/dL) and safety. Hypocalcemia was graded per CTCAE v5. Acute kidney injury (AKI) was defined using KGIDO criteria. Patients were followed-up for 56 days. Bivariate analyses were performed. Results A total of 40 patients were included with 18 in the denosumab group and 22 in the IVB group, of whom 15 (68%) received ZA and 7 (32%) received pamidronate. Baseline characteristics are described in Table 1. Patients with newly diagnosed MM composed 33% and 55% of the denosumab and IVB groups, respectively. All patients in the denosumab group received 120 mg except one who received 60 mg, while in the IVB group, dose reductions occurred in 5/15 patients who received ZA (median dose, 4 mg; range, 3.3-4) and 4/7 patients who received pamidronate (median dose, 60 mg; range, 30-90). Most patients received HC treatment as an inpatient (58% inpatient vs. 42% outpatient). A minority of patients had received IVBs in the past 90 days. The mean CSC was 12.5 mg/dL (standard deviation [SD], 1.40) and 13.3 mg/dL (SD, 2.39) in the denosumab and IVB groups, respectively. Baseline serum creatinine (SCr) was higher and creatinine clearance (CrCl) was lower in the denosumab group (median SCr, 2.06 vs. 1.24 mg/dL, p=0.048; median CrCl, 33 vs. 48 mL/min, p=0.048). The CR rate by day 3-4 was 92% and 94% in the denosumab and IVB groups, respectively (p=NS). HC relapse occurred in 2 (12%) and 6 (29%) patients in the denosumab and IVB groups, respectively (p=0.257). Incidence of grade 1 hypocalcemia was similar between groups; however, incidence of grade ≥2 hypocalcemia was higher in the denosumab group. Incidence of new AKI was 28% (5/18) in the denosumab group 23% (5/22) in the IVB group (p=0.71). No patients in the denosumab group received an additional dose of denosumab within 14 days of initial dose. Three patients in the IVB group received an additional dose of an IVB within 14 days of initial dose. One patient, who was in the denosumab group, had refractory hypercalcemia and had not achieved CR at day 56. Conclusions We describe our experience with denosumab and IVB for the management of HC in patients with MM. The CR rate at 3-4 days was similar with either agent in our MM only population that was not bisphosphonate refractory. A higher incidence of grade 2 hypocalcemia was noted in the denosumab group. Conclusions on renal safety are limited by the small sample size and that patients in the denosumab group had a higher SCr on presentation. Denosumab and IVB represent acceptable agents for the management of HC in MM patients with further investigation necessary in those with renal dysfunction. Disclosures Lei: Fresenius Kabi USA: Consultancy; Trapelo Health: Consultancy; Bluebird Bio: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current equity holder in publicly-traded company; Clovis Oncology: Current equity holder in publicly-traded company; Blueprint Medicines: Divested equity in a private or publicly-traded company in the past 24 months. Lou:Fresenius Kabi USA: Consultancy. Raje:Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Astrazeneca: Consultancy. Yee:Karyopharm: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Denosumab is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. We describe the use of denosumab for hypercalcemia of malignancy in a multiple myeloma only patient population that is not bisphosphonate refractory. The use of denosumab for these patients was part of normal clinical practice in adherence to institutional policies and guidelines.

scholarly journals Health-Related Quality of Life Outcomes for Patients with Transfusion-Dependent Beta-Thalassemia Treated with Luspatercept in the Believe Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-9
Author(s):  
Maria Domenica Cappellini ◽  
Ali T. Taher ◽  
Antonio Piga ◽  
Farrukh Shah ◽  
Ersi Voskaridou ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Research Funding ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Meaningful Improvement ◽  
Sf 36 ◽  
La Jolla ◽  
Domain Scores

Introduction: Patients (pts) with transfusion-dependent (TD) β-thalassemia may require long-term red blood cell transfusions (RBCT) that can lead to iron overload and associated complications, which impact negatively on health-related quality of life (HRQoL). Administration of RBCT provides transient relief from anemia-related symptoms associated with β-thalassemia; reduction of RBCT may increase anemia-related symptoms and thereby worsen HRQoL. The phase 3 BELIEVE study (NCT02604433) showed that the first-in-class erythroid maturation agent luspatercept provided clinically meaningful reduction in RBCT burden, but the impact of luspatercept on HRQoL is not well understood. This analysis assessed the effect of luspatercept plus best supportive care (BSC, including RBCT, iron chelation therapy) vs placebo (PBO) plus BSC on HRQoL in pts with TD β-thalassemia. Methods: Pts received luspatercept (starting dose 1.0 mg/kg with titration up to 1.25 mg/kg every 3 weeks) or PBO, subcutaneously for ≥ 48 weeks plus BSC. HRQoL was assessed using the generic 36-item Short Form Health Survey (SF-36) and the thalassemia-specific Transfusion-dependent Quality of Life questionnaire (TranQol), at screening (≤ 4 weeks prior to first study dose) and every 12 weeks up to 48 weeks of treatment. The HRQoL evaluable population included all pts who completed the HRQoL assessment at screening and ≥ 1 post-screening assessment visit. The TranQol and SF-36 were considered complete if ≥ 75% and ≥ 50% of items, respectively, were answered at a given time point. The primary analysis assessed changes from baseline between groups up to Week 48. The primary domains of interest were: TranQol total score and Physical Health (PH); and the SF-36 Physical Component Summary (PCS), Physical Functioning (PF), and General Health (GH). Other domains were considered exploratory domains. Changes from baseline were compared using ANCOVA models adjusting for baseline domain scores and geographic region. In exploratory analyses, the proportion of pts achieving a clinically meaningful improvement in domain scores were compared between pts on luspatercept achieving a clinical response (≥ 50% reduction in RBCT burden over 12 weeks; ≥ 33% reduction in RBCT burden over 12 weeks; transfusion independence [TI] any 8 weeks; or TI any 12 weeks), and PBO. Results: 336 pts were randomized to treatment; 224 to luspatercept and 112 to PBO. The HRQoL evaluable population was 212 (94.6%) in the luspatercept arm and 104 (92.9%) in the PBO arm. HRQoL questionnaire compliance rates among pts still on treatment were > 87.5% for both questionnaires at Week 48. Baseline HRQoL scores were similar to the US general population for most SF-36 domains, although GH, Role-Emotional, and Role-Physical domain scores were impaired in the BELIEVE population. Mean scores on all primary and exploratory domains were stable over time in both treatment groups and did not differ between treatment groups at Week 24 and 48. When considering responders to luspatercept, pts receiving luspatercept and achieving a ≥ 50% reduction in RBCT burden over 12 weeks were significantly more likely than pts receiving PBO to have a clinically meaningful improvement in PCS (31.1% vs 16.5%; P = 0.024), and PF (30.0% vs 13.2%; P = 0.007) at Week 48 (Table). Statistically significant differences between luspatercept and PBO were also seen among pts achieving TI for any 8 or any 12 weeks for some SF-36 domains, but no statistical difference was seen in pts achieving a ≥ 33% reduction in RBCT burden for either SF-36 or TranQol domains although the proportion of pts with improved scores was higher with luspatercept, especially at Week 48. Conclusions: Overall, the addition of luspatercept to BSC reduced transfusion burden while sustaining TranQol and SF-36 HRQoL scores over time through Week 48 compared with those receiving PBO. Pts with TD β-thalassemia responding to luspatercept were more likely to achieve clinically meaningful improvements in HRQoL compared with PBO. Disclosures Cappellini: Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics, Novartis, Vifor Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Taher:Silence Therapeutics: Consultancy; Vifor Pharma: Consultancy, Research Funding; Ionis Pharmaceuticals: Consultancy; BMS: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding. Piga:BMS: Research Funding; Novartis: Research Funding. Shah:Novartis, BMS: Consultancy, Honoraria, Speakers Bureau; Bluebird Bio: Consultancy, Honoraria; IQVIA: Consultancy, Membership on an entity's Board of Directors or advisory committees. Voskaridou:ADDMEDICA Company: Consultancy, Research Funding; BMS: Consultancy, Research Funding; ACCELERON Company: Consultancy, Research Funding; PROTAGONIST Company: Research Funding; GENESIS Company: Consultancy, Research Funding; NOVARTIS Company: Research Funding. Viprakasit:Agios Pharmaceuticals, Ionis Pharmaceuticals, La Jolla Pharmaceuticals, Protagonist Therapeutics, Vifor Pharma: Consultancy, Research Funding; BMS, Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Porter:Silence Therapeutics: Honoraria; La Jolla Pharmaceuticals: Honoraria; Vifor Pharmaceuticals: Honoraria; Protagonist Therapeutics: Honoraria; BMS: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy, Honoraria; bluebird bio, Inc.: Consultancy, Honoraria. Hermine:AB Science: Consultancy, Current equity holder in publicly-traded company, Honoraria, Patents & Royalties, Research Funding; BMS, Alexion, Novartis, Inatherys: Research Funding. Neufeld:Takeda: Consultancy; Octapharma: Consultancy; Novo Nordsik: Consultancy; genetech: Consultancy; Bayer: Other: DSMB; Imara Pharma: Other: DSMB service; ApoPharma/Chiezi: Other: DSMB service; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Acceleron Pharma: Consultancy, Other: DSMB. Thompson:BMS: Consultancy, Research Funding; Baxalta: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Biomarin: Research Funding. Tang:BMS: Current Employment, Current equity holder in publicly-traded company. Yu:Evidera: Current Employment. Guo:BMS: Consultancy. Shetty:BMS: Current Employment, Current equity holder in publicly-traded company. Miteva:BMS: Current Employment. Zinger:Celgene, a Bristol Myers Squibb company: Current Employment. Backstrom:Acceleron Pharma: Current Employment, Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company. Oliva:Abbvie: Consultancy; Amgen: Consultancy; Novartis: Consultancy; BMS: Consultancy, Honoraria, Patents & Royalties, Speakers Bureau; Alexion: Consultancy; Apellis: Consultancy.

scholarly journals Post-Traumatic Stress Disorder (PTSD) Symptoms in Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 44-45
Author(s):  
Hermioni L. Amonoo ◽  
Areej El-Jawahri ◽  
Thomas W. LeBlanc ◽  
Alison R. Kavanaugh ◽  
Jason A. Webb ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Research Funding ◽  
Stress Disorder ◽  
Ptsd Symptoms ◽  
Post Traumatic Stress ◽  
Advisory Committees ◽  
Post Traumatic ◽  
Clinically Significant

Background: Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy face a life-threatening illness, experience a prolonged, isolating hospitalization, and endure substantial physical and psychological symptoms. Some patients with AML experience traumatic stress as a result of their diagnosis and illness course. As traumatic stress reactions can negatively impact patients' QOL, mood, and clinical outcomes, it is essential to understand the extent of this trauma, its clinical manifestations, and risk factors to inform targeted management strategies. Post-traumatic stress disorder (PTSD), characterized by experiencing a traumatic event, is a common stress related disorder in cancer populations. Despite the potential link between AML and PTSD, data are limited regarding risk and risk factors of PTSD symptoms in this population. Methods: We conducted a secondary analysis of 160 patients with high-risk AML hospitalized to receive intensive chemotherapy. We used the Post-Traumatic Stress Disorder Checklist-Civilian Version to assess PTSD symptoms at one month after diagnosis of AML. We used the Brief COPE, and Functional Assessment of Cancer Therapy-Leukemia at baseline and week-2 during hospitalization to assess coping and quality of life (QOL), respectively. We then used multivariate regression models to assess the relationship between PTSD symptoms at one month and patient baseline sociodemographic factors, coping, and QOL. Results: Twenty-eight percent of patients reported clinically significant PTSD symptoms, describing high rates of intrusion (92%), avoidance (100%), and hypervigilance (97%). Among those who did not have clinically significant PTSD symptoms, 27%, 26%, and 23% of patients reported clinically significant intrusion, avoidance, and hypervigilance symptoms, respectively. In adjusted analyses, higher baseline QOL (B= -.22, p= <.001) and less decline in QOL during hospitalization (B= -.17, p=.018) were associated with fewer PTSD symptoms. The use of approach-oriented coping (B= -.72; p= .018) was also associated with fewer PTSD symptoms, while the use of avoidant coping was not significantly associated with PTSD symptoms. Conclusion: A substantial proportion of patients with AML report clinically significant PTSD symptoms at one month after initiating intensive chemotherapy. These findings highlight the need to routinely screen, assess, and manage PTSD symptoms in all patients with AML. Patients' baseline QOL, coping strategies, and extent of QOL decline during hospitalization are important risk factors for PTSD symptoms, underscoring potential intervention targets in future studies to reduce the impact of PTSD in this population. Disclosures LeBlanc: Heron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Medtronic: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; American Cancer Society: Research Funding; BMS: Research Funding; Duke University: Research Funding; NINR/NIH: Research Funding; Jazz Pharmaceuticals: Research Funding; UpToDate: Patents & Royalties; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; CareVive: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Flatiron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hobbs:Merck: Research Funding; Incyte: Research Funding; Celgene/BMS: Honoraria; Novartis: Honoraria; Jazz: Honoraria; Bayer: Research Funding; Constellation: Honoraria, Research Funding. Brunner:Novartis: Research Funding; AstraZeneca: Research Funding; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Luger:Daiichi-Sankyo: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Acceleron: Honoraria; Agios: Honoraria; Loxo Oncology: Honoraria; Onconova: Research Funding; Kura: Research Funding; Hoffman La Roche: Research Funding; Ariad: Research Funding; Biosight: Research Funding. Bhatnagar:KITE: Membership on an entity's Board of Directors or advisory committees; KaryoPharm Therapuetics: Research Funding; Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Continuous Mobile Wearable Bio-Monitoring of Newly Diagnosed Multiple Myeloma Patients Undergoing Initial Chemotherapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4751-4751
Author(s):  
Elizabet Tavitian ◽  
Donna Mastey ◽  
Meghan Salcedo ◽  
Andrew Zarski ◽  
Aisara Chansakul ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Baseline Period ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Activity Measurements ◽  
Bio Monitoring

Abstract Introduction The current standard to assess chemotherapy tolerability relies on patient self-reporting. However, as the sole mechanism of managing symptom burden, this may be inconsistent and fraught with bias. Mobile wearable health devices have the ability to monitor and aggregate objective activity and sleep data over long periods of time, but have not been systematically used in the oncology clinic. The aim of the study was to assess whether the use of mobile wearable technology establishes patterns of "sleep" and "wake" states in newly diagnosed Multiple Myeloma (NDMM) patients receiving therapy, and whether these patterns differ over time. Methods Patients presenting to the myeloma clinic at Memorial Sloan Kettering Cancer Center (MSKCC) with a new diagnosis of Multiple Myeloma and smart phone or tablet (iOS or Android) compatible with the Garmin Vivofit device were offered to participate in a mobile wearable bio-monitoring study. All eligible participants were required to receive primary chemotherapy treatment at a MSKCC facility. Treatment was determined by physician. NDMM patients were assigned to one of two cohorts (20 in each; Cohort A - patients <65 years; Cohort B - patients ≥ 65 years). Patients were given Garmin Vivofit devices and asked to download a Garmin Vivofit application and Medidata electronic patient reported outcome (ePRO) application on their phone or tablet. Patients were bio-monitored for physical activity and sleep during baseline period (1-7 days prior to chemotherapy initiation) and continuously up to 6 cycles of chemotherapy. Additionally, patients completed mobile ePRO questionnaires [(EORTC - QLQC30 and MY20) and brief pain inventory scales (BPI)] using the Medidata application at baseline and after each induction cycle. Activity, sleep data, and completed ePRO questionnaire data were automatically synced or transferred to Medidata Rave database through Medidata Sensorlink technology. In this abstract, we report initial results on prospective collection of activity measurements. Additional data from the health-related quality of life questionnaires and clinical outcomes will be presented at later date. Results Between February 2017-March 2018, 37 patients (19 males and 18 females) enrolled onto the study, with 20 in cohort A and 17 in cohort B. The mean age was 55 years (range 41-64) for cohort A and 72 years (range 65-82) for cohort B. Treatment regimens included Carfilzomib/Revlimid/Dexamethasone 14(38%), Velcade/Revlimid/Dexamethasone 10(27%), Daratumumab/Carfilzomib Revlimid/Dexamethasone, 7(19%), Cyclophosphamide/Velcade/Dexamethasone 3(8%), Revlimid/Dexamethasone 2(5%), and Velcade/Revlimid/Dexamethasone-Lite 1(3%). Twenty-four patients have completed the trial, and 7 remain active. Six patients came off-study due to the following reasons: lost devices (n=4), intolerable rash during cycle 3 (n=1), and incompletion of baseline activity (n=1). Three patients were excluded for incomplete data sets with no baseline data collection at the time of analysis. Fifteen patients were available for data review including 10 in cohort A and 5 in cohort B. Mean activity for cohort A was 6,437 steps/24 hr period (1,002 - 12,754) versus for cohort B was 3,218.37 steps/24 hr period (387 - 6,155) (p <0.05). In comparing pre- and post-therapy, overall mean activity for cohort A increased from 5,995 to 6,513 steps/24 hr, 8.6% increase (p=0.78), and for cohort B mean activity increased from 2,249 to 3,420 steps/24 hr, a 52% increase (p=0.2140). We assessed short term effects therapy initiation had on activity for NDMM patients by comparing percent changes in activity (steps/24 hrs) from baseline period to cycle 1 period. We found 3 patients had a >100% increase, 1 patient had 50-100% increase, and 11 patients had within +/- 50% change in activity from baseline. Conclusion Electronic mobile wearable device monitoring in symptomatic NDMM patients may be a useful tool to assess a patient's overall wellness and health as they are receiving chemotherapy. For three patients, we were able to capture a dramatic increase in activity after initiation of treatment. Overall activity in the elderly NDMM patients is decreased compared to younger patients. Mobile wearable monitoring may be an even more useful strategy for tracking elderly and unfit patients that are more prone to side effects, where the balance of response versus quality of life is paramount. Figure. Figure. Disclosures Mailankody: Physician Education Resource: Honoraria; Janssen: Research Funding; Takeda: Research Funding; Juno: Research Funding. Hassoun:Oncopeptides AB: Research Funding. Lesokhin:Squibb: Consultancy, Honoraria; Serametrix, inc.: Patents & Royalties: Royalties; Janssen: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Takeda: Consultancy, Honoraria. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Shah:Amgen: Research Funding; Janssen: Research Funding. Landgren:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Research Funding; Pfizer: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy. Korde:Amgen: Research Funding.

scholarly journals A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Entospletinib in Combination with Intensive Induction and Consolidation Chemotherapy in Adults with Newly Diagnosed N ucleophosmin 1-mutated Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1282-1282
Author(s):  
John C. Byrd ◽  
Jorge E. Cortes ◽  
Mark D. Minden ◽  
Thomas Oellerich ◽  
Eytan M. Stein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Acute Myeloid

Abstract Background: Spleen tyrosine kinase (SYK) is a component of both lymphoid and myeloid cell signaling pathways and has been implicated in the pathogenesis of a subset of acute myeloid leukemia (AML) defined by dysregulated expression of the HOXA9 and MEIS1 transcription factors. Entospletinib (ENTO) is an oral, selective SYK inhibitor that is acceptably tolerated when administered with intensive induction and consolidation in newly diagnosed AML patients. In a phase 2 study, following induction with cytarabine and daunorubicin (7+3) plus ENTO, higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) were observed in patients with rearrangements of the KMT2A (MLL) gene (MLL-r) and mutations of the nucleophosmin 1 (NPM1) gene, both of which are associated with aberrant expression of HOXA9 and MEIS1, as compared to patients without these mutations. In an exploratory analysis, patients with HOXA9/MEIS1 expression levels above the median experienced superior overall survival (OS) as compared to patients with expression levels below the median. In the AGILITY trial, we hypothesize that the addition of ENTO to intensive induction/consolidation in newly diagnosed patients with NPM1-mutated AML will improve the rate of CR without evidence of measurable residual disease (MRD-negative CR) post-induction and duration of event-free survival (EFS). Methods: AGILITY will be a global, multi-center, double-blind, placebo-controlled trial of ENTO in combination with cytarabine plus daunorubicin or idarubicin induction (7+3) and age-adjusted high-dose cytarabine (HiDAC) consolidation in newly diagnosed AML patients aged 18-75 years who are candidates for intensive induction and harbor a documented NPM1 mutation based on local or central mutation testing. Patients with co-mutated FLT3 (internal tandem duplication or tyrosine kinase domain) and for whom midostaurin with 7+3 is indicated are excluded. Patients will be stratified based on age (&lt;60 vs ≥60 years) and anthracycline administered during induction (daunorubicin vs idarubicin). Approximately 180 patients will be randomized to receive 7+3 induction and HiDAC consolidation with ENTO (400 mg orally twice daily) versus 7+3 induction and HiDAC with placebo. Patients with &lt;5% leukemic blasts after 1 cycle of induction will proceed to the first cycle of HiDAC consolidation while patients with ≥5% residual blasts will undergo a second induction cycle. Patients who do not achieve CR after 2 cycles of chemotherapy (either 2 induction cycles or 1 induction and 1 consolidation cycle) plus ENTO or placebo will be designated as induction treatment failures (ITF). Patients who achieve or remain in CR after 2 chemotherapy cycles will be evaluated for MRD in bone marrow based on enumeration of mutant NPM1 alleles using a molecular assay. Patients may receive up to 3 cycles of consolidation with HiDAC and ENTO or placebo beyond chemotherapy cycle 2 per their original randomized treatment assignment. The number of consolidation cycles and timing of hematopoietic stem cell transplant (HSCT) or other post-consolidation therapy (if any) is at the discretion of the investigator. All patients will be followed for relapse and survival. The primary endpoint will be the rate of MRD-negative CR (&lt;0.01% mutant NPM1 alleles). Patients without an evaluation of response and MRD after chemotherapy cycle 2 will be imputed as treatment failures for the analysis. A key secondary endpoint will be EFS, defined as time from randomization to the earliest occurrence of ITF, relapse from CR, or death from any cause. Patients without an event at the time of the EFS analysis will be censored at the last study evaluation they were event-free. EFS will be estimated using the Kaplan-Meier method and summarized by treatment group. Differences between treatment groups will be assessed with the log-rank test stratified by age (&lt;60 vs ≥60 years) and choice of anthracycline in induction (daunorubicin vs idarubicin). OS will be analyzed in a similar manner. Key exploratory endpoints will be the correlation between recurring genomic mutations and response or progression and longitudinal assessment of peripheral blood for detection of NPM1-m alleles among patients who achieve MRD-negative CR post-induction. An independent data-monitoring committee will monitor emerging safety and efficacy data from this trial on an ongoing basis. Disclosures Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Cortes: Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sun Pharma: Consultancy, Research Funding. Minden: Astellas: Consultancy. Oellerich: Roche: Consultancy; Gilead: Research Funding; Kronos Bio, Inc.: Consultancy; Merck KGaA: Consultancy, Research Funding. Stein: Syros Pharmaceuticals, Inc.: Consultancy; Daiichi Sankyo: Consultancy; PinotBio: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Syndax Pharmaceuticals: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy. Elder: PharPoint Research, Inc.: Current Employment. Kumar: Kronos Bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Bray: Kronos Bio, Inc.: Consultancy. DiMartino: Kronos Bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. OffLabel Disclosure: Entospletinib is an investigational therapy

scholarly journals Presence of Extrachromosomal DNA (ecDNA) Impacts Both Progression Free and Overall Survival and Is an Independent Poor Prognostic Marker in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 461-461
Author(s):  
Parth Shah ◽  
Anil Aktas-Samur ◽  
Mariateresa Fulciniti ◽  
Raphael Szalat ◽  
Masood A. Shammas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Board Of Directors ◽  
Copy Number ◽  
Research Funding ◽  
P Value ◽  
Newly Diagnosed ◽  
Extrachromosomal Dna ◽  
Publicly Traded ◽  
Advisory Committees

Abstract Background Focal amplifications and rearrangements drive tumor growth and evolution in cancer. Focally amplified regions often involve the juxtaposition of rearranged segments of DNA from distinct chromosomal loci into a single amplified region and nearly half of these regions can be explained by circular, extrachromosomal DNA (ecDNA) formation. Cancer-associated ecDNA shows a unique circular placing ecDNA at the interface of cancer genomics and epigenetics. As formation of ecDNA represents a manifestation of genomic instability, we have investigated presence and prognostic impact of ecDNA in multiple myeloma (MM). Methods Whole genome (WGS) and transcriptome (RNAseq) sequencing data from CD138 purified MM cells from 191 uniformly-treated newly diagnosed MM patients were used for this analysis. Copy number variants (CNV), single nucleotide variants (SNV) and structural variants (SV) were identified on all WGS samples using Facets, Mutect2 and Manta. Seed data from these CNV results was passed to the AmpliconArchitect tool to determine presence of focally amplified and rearranged segments of DNA. Seed CNV thresholds were set for a minimum CNV size of 100kb and a copy number of equal or greater to 5. Extrachromosomal calls were then annotated using the Amplicon Classifier to determine the presence of ecDNA. Multivariate survival analysis was performed after segregating samples into the conventional myeloma risk classifications including translocations, copy number alterations, ISS, age and mutations associated with risk. Differential expression analysis was performed on transcriptomic data using DEseq2. Results We identified 6.8% of the newly diagnosed patients with ecDNA, 12.5% with complex non-cyclic DNA amplifications and 10.1% with linear amplifications. ecDNA and complex events were targeting MM dependent genes, including MYC/PVT1, IRF4 as well as known driver genes such as CDYL and TRAF2. We further evaluated association between ecDNA, complex rearrangements, linear amplification and patients with none of these amplification types and found that patients with ecDNA had significantly poor PFS (median PFS 22 months vs. 41 months) and OS (median OS 41 months vs. 105 months). Patients having ecDNA in their MM cells did not show any significant enrichment for known translocations, double hit or TP53 mutations. In a multivariate model including ecDNA and all other known MM risk features, ecDNA was found to be an independent predictor of progression free survival.(HR 2.6, CI: 1.26 -5.6, p=0.0082) and overall survival (HR 7.94 CI:3.5-17.9 p &lt; 0.0001). Patients with ecDNA have higher mutational load probability(8798 vs 6982, effect size = 0.64 , probability is 91.1). However, this was not reflected in heterogeneity by using MATH score. We found that patients with ecDNA are likely to have BRAF mutations (OR= 25.07 [2.57 - 330 95% CI], p value = 0.002), however overall RAS/RAF pathway mutations were similar to other patients. Patients with ecDNA showed fragile DNA with more breaks (median segments 197 vs. 125.5, p value = 0.001). Although ecDNA is defined as copy number gain with fragments having 5 or more copies, overall genomic gain between ecDNA and other patients were similar. However, overall genomic loss in patients with ecDNA were higher than others (7% vs. 4.2%, p = 0.06). By differential gene expression analysis we noted 98 differentially expressed genes in MM cells with ecDNA. The downregulated geneset involved pathways responsible for cell death as well as the RAS pathway. Interestingly, CD38 was upregulated in the ecDNA dataset suggesting greater potential for CD38 targeting therapies in these patients. Conclusions ecDNA, as an unique marker of perturbed genomic integrity, is observed in a subset of patients and is an independent prognostic marker in newly diagnosed MM patients. As patients with ecDNA are not fully captured by other risk features its incorporation in an expanded definition of a high risk group of multiple myeloma should be investigated. Future studies will endeavor to explore the biological mechanism through which ecDNA are formed and influences outcomes in myeloma. Figure 1 Figure 1. Disclosures Richardson: Sanofi: Consultancy; GlaxoSmithKline: Consultancy; Karyopharm: Consultancy, Research Funding; AstraZeneca: Consultancy; AbbVie: Consultancy; Oncopeptides: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy; Protocol Intelligence: Consultancy; Celgene/BMS: Consultancy, Research Funding; Secura Bio: Consultancy; Regeneron: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Perrot: Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: 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; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria. Thakurta: Oxford University: Other: Visiting Professor; BMS: Current Employment, Current equity holder in publicly-traded company. Anderson: Gilead: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Munshi: Legend: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Adaptive Biotechnology: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Celgene: Consultancy; Pfizer: Consultancy.

Quality of Life During Early Tyrosine Kinase Inhibitor Treatment As Self-Reported by Chronic Myeloid Leukemia Patients Participating in a Prospective Observational Study (SIMPLICITY)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4435-4435
Author(s):  
Jorge E. Cortes ◽  
Michael J. Mauro ◽  
Stuart L. Goldberg ◽  
Ron Paquette ◽  
H. Jean Khoury ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Treatment Adherence ◽  
Treatment Satisfaction ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
The Impact

Abstract Abstract 4435 Background: Over the past decade, oral BCR-ABL inhibitors including imatinib, dasatinib and nilotinib have revolutionized chronic myeloid leukemia (CML) treatment. Clinical trials have provided evidence of improved outcomes with all three agents in the treatment of CML. However, limited information is available regarding the impact of disease and treatment on quality of life (QoL) in CML patients. Methods: SIMPLICITY is an ongoing 5-year USA/European prospective, observational cohort study (ClinicalTrials.gov ID: NCT01244750). Eligibility criteria include: newly diagnosed CML-CP, age ≥18 years and therapy with 1st-line imatinib, dasatinib or nilotinib at participating medical centers. The study aims to capture information on the use of these agents in clinical practice, including their impact on patient QoL. Through self-administered patient-reported outcomes (PRO) questionnaires, QoL and treatment-adherence data are being collected at 6-month intervals throughout study follow-up. Data from available initial PRO assessments of patients enrolled as of August 2011 are presented: Cancer Treatment Satisfaction Questionnaire (CTSQ), MD Anderson Symptom Inventory - CML (MDASI-CML), FACT-G (Functional Assessment of Cancer Therapy-General) and Morisky Medication Adherence Scale - 8 item (MMAS-8). Results: A total of 74 patients currently enrolled was included in this analysis of which 79.7% (n=59) received imatinib, 10.8% (n=8) received nilotinib and 9.5% (n=7) received dasatinib as 1st-line CML treatment. Median age was 57 years (range 19–94 years); a slightly higher proportion of patients were female (59.5%; n=44); and median time to completion of the PRO questionnaires from initiation of treatment was 383.5 days (range 4-1,225 days). Prior to completion of the PROs, mean treatment exposure was approximately 18 months for imatinib, 5 months for nilotinib and 4 months for dasatinib. Summary scores for the CTSQ, MDASI-CML and FACT-G are presented in Table 1. Due to small sample size, differences in scores between treatments were not statistically tested. At time of enrollment in the study, treatment satisfaction in this cohort was high (SWT score ± standard deviation [SD] =91.2 ±10.3). QoL, as measured by the FACT-G total and sub-scale scores, also indicated positive physical, social, emotional and functional well-being. Mean MDASI scores for Symptom Interference and Symptom Distress suggested the impact of symptoms was mild to moderate. From the MMAS-8, 71.8% (n=51) of patients reported medium/high adherence to their CML medication (scoring between 6–8 on an 8-point scale). Conclusions: Preliminary QoL evaluation suggests that newly diagnosed CML-CP patients are generally satisfied with treatment and report overall good health, although approximately 30% reported low adherence to their CML treatment. Initial assessment of the enrolled cohort suggests variance in treatment adherence patterns, as well as differences in the impact of symptoms by treatment; however, as these differences were not statistically tested, no firm conclusions can be drawn at this time. As patient enrollment continues, comparative effectiveness of these CML treatments and differences in QoL outcomes will be further observed. Disclosures: Cortes: Novartis: Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy. Mauro:BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Ariad: Research Funding. Goldberg:Novartis Pharmaceutical: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Paquette:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Khoury:BMS: Membership on an entity's Board of Directors or advisory committees. Hirji:BMS: Employment. Wagner:BMS: Employment. Joo:BMS: Employment. Davis:BMS: Employment.

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