Patient and Physician Preferences for Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) in Patients Not Candidates for Intensive Chemotherapy

Abstract Background The number of targeted antileukemic therapies for the treatment of AML has increased over the past decade. However, for patients who are not candidates for high intensive chemotherapy (HIC), a better understanding is needed of what treatment attributes patients and physicians value and how their preferences differ to potentially improve treatment satisfaction. Objective To understand the impact of treatment attributes on treatment selection, we quantified the preferences of: a) patients newly diagnosed with AML who are not candidates for HIC; and, b) the physicians who treat them. Methods A discrete choice experiment (DCE) was performed to quantify the extent to which treatment attributes impact patients' and physicians' treatment decisions in various scenarios. A literature review was conducted to identify treatment attributes important to patients with AML. Following the review, one-on-one phone interviews were conducted with patients (United States [US], n=3; United Kingdom [UK], n=3) and physicians (US, n=2; UK, n=2) to finalize the attributes and levels included in the DCE. Patients who were eligible to participate in the online survey were adults with a self-confirmed AML diagnosis, who had not relapsed or been refractory to treatment, had not received a stem cell transplant, and had not received HIC or met one of the following criteria: aged ≥75 years, diagnosis of congestive heart failure, chronic kidney disease, or other types of cancer, or ECOG score of 3 or 4. Physicians included hematologists/ oncologists treating >5 patients with AML over the past year. The web-based DCE included choice cards showing 2 hypothetical treatment profiles with 6 attributes (chance of 2-year overall survival [OS], average quality of life [QoL], risk of serious infections, risk of grade 3/4 nausea, chance of achieving transfusion independence, and duration of hospitalization per year) at varying levels. Participants chose a preferred treatment for each choice card. Conditional logit regression models were used to estimate preference weights and to analyze the impact of treatment attributes on participants' choices. Results The DCE was completed by 77 patients newly diagnosed with AML who had not received HIC (US, n=47; UK, n=30) and 145 physicians (US, n=48; UK, n=52; Canada, n=29; Australia, n=16). Mean patient age was 71.4 years; 51.9% were female. Mean (SD) time since AML diagnosis was 8.3 (8.2) months. Most physicians were hematologists (81.4%) and saw a median of 30 AML patients yearly. For patients, duration of hospitalization (decrease from 6 to 2 weeks/year) was the most important attribute followed by average QoL (increase from 50 to 85 on a 100-point QoL scale) and chance of 2-year OS (increase from 15% to 40%; Figure). Based on these findings, we estimated that patients were willing to accept a decrease in 2-year OS (from 40% to 15%) or an increase in risk of serious infections (from 5% to 20%) to decrease time spent hospitalized (from 6 to 2 weeks per year). For physicians, chance of 2-year OS (from 15% to 40%) was the most important attribute followed by average QoL (increase from 50 to 85 on a 100-point scale), risk of serious infections (from 20% to 5%), and risk of grade 3/4 nausea and vomiting (from 20% to 1%; Figure). Based on these findings, we estimated that physicians were willing to accept an increased risk of grade 3/4 nausea and vomiting (from 10% to 20%) in exchange for decreased time in hospital (from 6 to 2 weeks per year) and increased chance of achieving transfusion independence (from 35% to 55%) when other treatment attributes remained stable. Conclusion Significant differences in treatment attribute importance for patients with newly diagnosed AML who had not received HIC were observed between patients and physicians. Patients most valued treatments that reduced hospitalization duration while physicians most valued treatments that improved chance of 2-year OS. These differences highlight the importance of a shared decision-making process when choosing treatments for patients with AML ineligible for HIC. However, given the variability among individual patients, it may be particularly worthwhile for physicians to initiate a discussion with patients prior to treatment selection to determine what treatment attributes each patient values most. Treatment selection could then be tailored based on attributes most valued by the patient and likely lead to improved treatment satisfaction. Figure 1 Figure 1. Disclosures Zhou: Astellas Pharma, Inc.: Consultancy. Yang: Astellas Pharma, Inc.: Consultancy. Song: Astellas Pharma, Inc.: Consultancy. Marshall: Astellas Pharma, Inc.: Consultancy; Arthur JE Child Chair: Other: Indirectly related salary support. Griffin: Novartis: Patents & Royalties: Post marketing royalties from midostaurin; Astellas Pharma, Inc.: Consultancy. Saini: Astellas Pharma, Inc.: Consultancy, Honoraria. Shah: Astellas Pharma, Inc.: Current Employment; University of Michigan School of Public Health Department of Health Management and Policy Alumni Board: Other: Chair-Elect.

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6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150)

Blood Cancer Journal ◽

10.1038/s41408-021-00555-8 ◽

2021 ◽

Vol 11 (10) ◽

Author(s):

Andrew H. Wei ◽

Panayiotis Panayiotidis ◽

Pau Montesinos ◽

Kamel Laribi ◽

Vladimir Ivanov ◽

...

Keyword(s):

Complete Response ◽

Intensive Chemotherapy ◽

Primary Analysis ◽

Free Survival ◽

Risk Of Death ◽

Transfusion Independence ◽

Frontline Treatment ◽

Grade 3 ◽

Low Dose Cytarabine

AbstractVIALE-C compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine (+LDAC) in patients with untreated AML ineligible for intensive chemotherapy. Overall, 211 patients were enrolled (n = 143, venetoclax; n = 68, placebo). At the primary analysis, the study did not meet its primary endpoint of a statistically significant improvement in overall survival (OS), however, ~60% of patients had been on study for ≤6-months. Here, we present an additional 6-months of follow-up of VIALE-C (median follow-up 17.5 months; range 0.1–23.5). Median OS was (venetoclax +LDAC vs. placebo +LDAC) 8.4 vs. 4.1 months (HR = 0.70, 95% CI 0.50,0.99; P = 0.040); a 30% reduction in the risk of death with venetoclax. Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were 48.3% vs. 13.2%. Transfusion independence rates (RBC) were 43% vs.19% and median event-free survival was 4.9 vs. 2.1 months (HR = 0.61; 95% CI 0.44,0.84; P = 0.002). These results represent improved efficacy over the primary analysis. Incidence of grade ≥3 adverse events were similar between study arms and overall safety profiles were comparable to the primary analysis. These data support venetoclax +LDAC as a frontline treatment option for patients with AML ineligible for intensive chemotherapy.This trial was registered at www.clinicaltrials.gov as #NCT03069352.

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Impact of age on efficacy and safety of daratumumab in combination with lenalidomide and dexamethasone (D-Rd) in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (NDMM): MAIA.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8035 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8035-8035

Author(s):

Saad Zafar Usmani ◽

Thierry Facon ◽

Shaji Kumar ◽

Torben Plesner ◽

Philippe Moreau ◽

...

Keyword(s):

Dose Intensity ◽

Standard Of Care ◽

Newly Diagnosed ◽

Median Dose ◽

Phase 3 ◽

Risk Of Progression ◽

Grade 3 ◽

The Impact ◽

Clinical Trial Information

8035 Background: D-Rd significantly reduced the risk of progression/death by 44% in transplant-ineligible NDMM pts vs Rd in the phase 3 MAIA study. To examine the impact of age on efficacy/safety of D-Rd vs Rd in this population, a subgroup analysis was conducted in pts <75 and ≥75 y of age. Methods: Transplant-ineligible NDMM pts were randomized 1:1 to Rd ± DARA; stratification was based on age (<75 vs ≥75 y), ISS (I, II, III), and region (North America vs Other). Pts received 28-day cycles of either R 25 or 10 mg (based on renal function) PO QD on Days 1-21 and either d 40 or 20 mg (based on age or BMI) PO/IV weekly until progression. In the D-Rd arm, pts received daratumumab 16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter until progression. PFS is the primary endpoint. Results: Among 737 randomized pts (D-Rd, n=368; Rd, n=369), 321 (44%) were ≥75 y of age. For D-Rd vs Rd, relative median dose intensity for R was 79% vs 93% for <75 y subgroup and 66% vs 89% for ≥75 y subgroup, respectively. After median follow-up of 28 mo, significant PFS benefit of D-Rd vs Rd was maintained in both <75 and ≥75 y subgroups (Table). Deeper responses and MRD-negative rate (10-5 threshold) remained higher with D-Rd vs Rd in both subgroups (Table). Most common (≥10%; D-Rd/Rd) grade 3/4 TEAEs in ≥75 y pts were neutropenia (60%/41%), lymphopenia (19%/12%), anemia (16%/22%), pneumonia (15%/10%), leukopenia (12%/6%), and thrombocytopenia (8%/11%). Fewer pts receiving D-Rd vs Rd discontinued treatment due to TEAEs (<75 y: 5% vs 12%; ≥75 y: 10% vs 21%). Conclusions: D-Rd pts received less R vs Rd group regardless of age. Efficacy of D-Rd in <75 and ≥75 y pts was consistent with the ITT population, and D-Rd demonstrated acceptable tolerability regardless of age. Together with the phase 3 ALCYONE study, these studies confirm clinical benefit of daratumumab plus standard-of-care in transplant-ineligible NDMM pts ≥75 y of age. Clinical trial information: NCT02252172. [Table: see text]

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Continued Improvement in Survival in Multiple Myeloma and the Impact of Novel Agents

Blood ◽

10.1182/blood.v120.21.3972.3972 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3972-3972 ◽

Cited By ~ 6

Author(s):

Shaji K. Kumar ◽

Angela Dispenzieri ◽

Morie A Gertz ◽

Martha Q Lacy ◽

John A Lust ◽

...

Keyword(s):

Overall Survival ◽

Research Funding ◽

Initial Therapy ◽

Novel Agents ◽

The Novel ◽

Newly Diagnosed ◽

Entire Cohort ◽

The Past ◽

The Impact

Abstract Abstract 3972 Background: The treatment paradigm for myeloma has undergone a dramatic shift in the past decade with the introduction of the novel agents and their application at every stage of the treatment. We and others had previously shown that survival of patients with myeloma had improved in the earlier half of the last decade and attributed this to a combination of novel therapies as well as increased use of stem cell transplant. It is not clear if this momentum in improving survival has been maintained. We examined the survival trends of patients with newly diagnosed myeloma seen within the past decade to examine this question. Patients and Methods: We studied 1056 patients with newly diagnosed myeloma, who were seen at Mayo Clinic between January 1, 2001 and December 31, 2010; who were seen within 30 days of their diagnosis. For examination of the time trends, we grouped the time interval into two five year periods, 2001–2005 and 2006–2010. Survival was estimated using Kaplan Meier method and survival curves were compared by log rank test. Impact of various prognostic factors was evaluated using Cox proportional hazards test. Results: The median age at diagnosis was 65 (range; 22–92), and 59% were male. The median estimated follow up for the entire cohort was 4.6 years (95% CI; 4.4, 4.9) and 57% of the patients were alive at last follow up. The median overall survival (OS) for the entire cohort was 5.4 years (95% CI; 5, 6.3). The overall survival for patients in the 2001–2005 group was 4.6 years compared with not reached for the 2006–2010 cohort (P< 0.001). The five-year estimated OS was 48% for the earlier group compared with 66% for the latter group. The estimated 1-year survival was 90% for the recent cohort compared with 83% for the earlier cohort, suggesting improvements in the early mortality. Interestingly, the improvement was predominantly seen in the older age group (>65 years; 49%). The 5-year survival of the older patients improved significantly from 31% (2001–2005) to 56% (2006–2010) (P<0.001). In contrast, among younger patients (≤65 years of age), the 5-year survival improved only marginally from 63% (2001–2005) to 73% (2006–2010) (P=NS). One or more novel agents (Lenalidomide, thalidomide or bortezomib) were used as part of initial therapy in 631 (62% of 1021 in whom treatment data was available). The OS among of this group was 7.3 years (95% CI; 5.9, NR) compared with 3.8 years (95% CI; 3.1, 4.6). In a multivariate model that included both use of novel agent and the year group, only the novel agent use was associated with improved survival suggesting that the improvement in the survival is related to the increased use of novel agents in the initial therapy. No significant differences were observed between the groups in terms of conventional prognostic factors. Conclusions: The current results confirm continued improvement in the overall survival of patients, even within the last 10 year period, and highlight the impact of initial therapy with novel agents. Most importantly, we demonstrate that the improved survival has primarily benefited older patients. Our study highlights that urgent need for additional new agents to provide further survival improvement for younger patients, and in order achieve a cure for this disease. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Cephalon: Research Funding; Genzyme: Research Funding. Dispenzieri:Celgene: Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Janssen Research & Development: Research Funding. Gertz:Binding Site: Honoraria.

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Survival trends in patients diagnosed with metastatic prostate cancer: A nationwide analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.171 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 171-171

Author(s):

John Thomas Helgstrand ◽

Nina Klemann ◽

Birgitte Grønkaer Toft ◽

Ben Vainer ◽

Klaus Brasso ◽

...

Keyword(s):

Prostate Cancer ◽

Lead Time ◽

Metastatic Prostate Cancer ◽

Randomized Clinical Trials ◽

Patient Characteristics ◽

Newly Diagnosed ◽

The Past ◽

Specific Mortality ◽

Cox Analysis ◽

The Impact

171 Background: The risk of prostate cancer (PCa)-death in men diagnosed with metastatic (M+) PCa is high. During the past decade, new life-prolonging therapies have been approved for the treatment of advanced PCa. Even though demonstrated in randomized clinical trials, the impact of these advancements on mortality of men with newly diagnosed M+ PCa has not been described in a nation-wide setting. Methods: In the Danish Prostate Cancer Registry (DaPCaR), all men diagnosed with M+ PCa in Denmark from 1995 to 2011 were identified. Patients were grouped according to the year of diagnosis; 1995-2000, 2001-2005 and 2006-2011. In a competing risk setting, the 5-year cumulative incidences of PCa, other-cause, and overall death were calculated. Multivariate cause-specific Cox analysis was performed. Results: A total of 1,892 (1995-2000), 2,329 (2001-2005), and 2,653 (2006-2011) men were included (total: 6,874). Patient characteristics at diagnosis showed essential differences as median age and median PSA decreased by 1.0 year (74.1 to 73.1) and 134 ng/mL (276 to 142), respectively, in the period studied. The 5-year PCa-specific mortality decreased by 17.0% from 72.8% (1995-2000) (95%CI: 70.8% – 74.8%) to 55.8% (2006-2011) (95%CI: 53.9% – 57.7%), p < 0.0001. The 5-year other-cause mortality increased by 5.7% from 11.4% (95%CI: 9.9% – 12.8%) to 17.1% (95%CI: 15.6 – 18.6), p < 0.0001. The risk of PCa-death decreased for patients diagnosed in 2000-2005; HR: 0.69 (95%CI 0.61-0.79) and for patients diagnosed in 2006-2011; HR: 0.53 (95%CI 0.47-0.61) compared to patients diagnosed in 1995-2000, when adjusting for age, PSA, and Gleason score (GS) in the statistical analysis. Conclusions: A significant reduction in 5-year PCa-specific mortality was observed in a nationwide cohort of patients diagnosed with M+ PCa since 1995. Changes in age and PSA at diagnosis suggest that lead-time introduced by increased PSA use may have affected the results. However, in multivariate analysis, a significant reduction in hazard of almost 50% was observed when adjusting for age, PSA, and GS. Only minor changes in other cause mortality were found, which suggests that the improvement to a large extend can be credited to improved management of men with advanced PCa.

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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 ◽

10.1182/blood.v118.21.4435.4435 ◽

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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Transfusion Requirements and Hospitalization during First Line Treatment Among Newly Diagnosed Acute Myeloid Leukemia Patients Who Were Ineligible for Intensive Chemotherapy

Blood ◽

10.1182/blood-2018-99-117247 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4849-4849

Author(s):

Cat N. Bui ◽

Thomas Marshall ◽

Rajesh Kamalakar ◽

Tracey Posadas ◽

Jalaja Potluri

Keyword(s):

Myeloid Leukemia ◽

Transfusion Requirement ◽

Intensive Chemotherapy ◽

Newly Diagnosed ◽

First Line ◽

Employment Equity ◽

Transfusion Independence ◽

Transfusion Requirements ◽

Equity Ownership ◽

The Mean

Abstract Background: Newly diagnosed acute myeloid leukemia (ND AML) patients (pts) ineligible for intensive chemotherapy have limited treatment options. Most commonly used low intensity regimens are azacitidine (AZA), decitabine (DEC), or low-dose cytarabine (LDAC). These patients often have low blood counts that may contribute to poor quality of life (QoL) due to high risk for infections and may require transfusion of blood products. The objective of this study was to describe the patient characteristics, treatment patterns, and quantify the clinical outcomes (i.e., transfusion requirements infections and hospitalizations (hosp) among ND AML pts ineligible for intensive chemotherapy who received currently available therapies as first-line (1L) treatment in a real-world cohort. Methods: Eligible pts were found in the de-identified Optum© Clinformatics® Data Mart between 1/1/2010 and 6/30/2017 and had the following: AML at ≥2 encounters (ICD-9/10 codes) at least 30 days apart, ≥ 60 yrs. at diagnosis (dx), and ≥6 months (mo) benefit coverage before and ≥ 3 mo post dx. 1L treatment date (tx-index) was the date of first monotherapy (AZA, DEC, or LDAC) after AML diagnosis. 1L treatment duration was from tx-index to the end of study (EOS) defined as either end of 1L treatment, end of benefit coverage, relapse, or 12/31/2017. Transfusion independence (TI) during 1L treatment was defined as having neither platelets nor red blood cells (RBC) for ≥56 consecutive days (56-day TI). Patients with < 56 days of observation time from tx-index were not classified as achieving ≥56-day TI. During 1L treatment, transfusion support was defined as patients receiving either platelets and/or RBC regardless whether or not patients achieved ≥56-day TI. Sample selection and creation of analytic variables were performed using the Instant Health Data (IHD) platform (BHE, Boston, MA). Statistical analyses were undertaken with SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). Results: Among 785 eligible pts, 82.0% had Medicare Advantage, 59.2% were male, and the mean (median; range) age was 74.7 (75.0; range 60.0-89.0) yrs. The mean (median; range) baseline comorbidity score (measured by Quan Charlson Comorbidity Index, CCI) was 1.5 (1.0; 0-11), with an available follow-up period of 13.6 (10.6; 3.0-88.5) mo. As1L treatment, majority of pts received AZA (n=422, 53.8%) followed by DEC (n=337, 43.0%) and LDAC (n=26, 3.3%) and the mean (median; range) duration of treatment was 5.6 (3.7; 0.03-52.0) mo. A total of 4.5% (35) patients had major or minor GI hemorrhage, 1.9% (15) brain hemorrhage, and 48.7% (382) had infections of all grades (AZA: 202/422, 47.9%; DEC: 170/337, 50.5%; LDAC: 10/26, 38.5%). Prior to receiving 1L treatment, 48.0% (377/785) of patients required transfusion of either platelets and/or RBC (Table 1). During 1L treatment, 73.3% (575) of pts received transfusion support with a mean (median; range) of 8.5 (5.0; 1-181) transfusions of either platelets and/or RBC. Among 377 patients with transfusion support prior to 1L treatment, 33.7% (127/377) of patients achieved ≥ 56-day TI during 1L treatment (Table 1). Multivariate logistic regression showed pts with baseline transfusion requirement were less likely to achieve ≥56 consecutive day TI during 1L treatment vs. pts without baseline transfusion requirements (33.7% vs. 58.6%; OR = 0.37; 95% CI = 0.27 - 0.50; P < 0.001) with the current treatments. Among 785 patients during 1L treatment, the mean (median; range) number of hospitalizations was 0.91 (1.0; 0-8). A total of 53.1% (417) had ≥ 1 hospitalization; the mean (median; range) length of an inpatient stay was 10.9 (7.0; 1-97) days for these patients; and 49.4% (206), 75.1% (313), and 87.3% (364) of patients were admitted within 30, 60, 90 days of tx-index, respectively. Conclusions: This real-world study in ND AML patients showed transfusion burden on patients with the currently available non-intensive treatment with AZA and DEC being the most commonly used agents. Most (61.5%-80.1%) of the pts required transfusions for platelets and /or RBC and less than 40% (0%-38.6%) of the patients with baseline transfusion requirement achieved ≥56 consecutive days of transfusion independence anytime while receiving their 1L treatment. Additional research is warranted to understand the correlation between response to treatment and transfusion independence and subsequent impact on hospitalization and infections. Disclosures Bui: AbbVie: Employment. Marshall:AbbVie: Employment, Equity Ownership. Kamalakar:AbbVie: Employment. Posadas:AbbVie: Employment. Potluri:AbbVie: Employment, Equity Ownership.

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Oral Arsenic Trioxide in the Frontline Treatment of Newly-Diagnosed Acute Promyelocytic Leukemia: A 5-Year Prospective Cohort Study

Blood ◽

10.1182/blood-2018-99-111801 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3990-3990

Author(s):

Harinder Gill ◽

Cyrus R Kumana ◽

Yok-Lam Kwong

Keyword(s):

High Risk ◽

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Conflicts Of Interest ◽

Reference Value ◽

Promyelocytic Leukemia ◽

Newly Diagnosed ◽

Frontline Treatment ◽

Grade 3 ◽

The Impact

Abstract Introduction and objectives Intravenous arsenic trioxide (As2O3) has been tested in the frontline treatment of newly-diagnosed acute promyelocytic leukemia (APL). We have formulated an oral preparation of As2O3 (oral-As2O3), and shown that it is efficacious for APL in when used in maintenance and re-induction protocol. In this study, we evaluated the use of oral-As2O3 in the frontline treatment of APL. The main objective of the study was to define the impact of upfront use of oral-As2O3 in newly-diagnosed patients. Methods Patients. Patients with newly-diagnosed APL in eight regional hospitals in Hong Kong were identified. Arsenic-induction cohort. Induction comprised oral-As2O3 (10 mg/day, reduced to 5 mg/day in patients with serum creatinine >upper reference value; as 1 mg/ml solution), ATRA (45 mg/m2/day in 2 divided doses) and ascorbic acid (1 g/day) (AAA regimen), administered for six weeks. Three days of daunorubicin (50 mg/m2/day) were administered to patients aged <70 years, and omitted for those aged ≥70 years. For patients not receiving daunorubicin, if the white blood cell count (WBC) rose to >5 x 109/L, hydroxyurea (2-3 g/day) was used for cytoreduction. Consolidation regimen. On confirmation of CR1, two monthly consolidations comprising daunorubicin (50 mg/m2/day x 2) and cytarabine (100 mg/m2/day x 5) were administered to patients aged <70 years. For patients aged ≥70 years, consolidation with two monthly cycles of AAA (2 weeks/cycle) was instead administered. Bone marrow examination was performed two weeks after completion of consolidation. Maintenance regimen. All patients received maintenance AAA, given two weeks every eight weeks for two years. Results In a 5-year period (January 1, 2013-March 31, 2018), there were 104 consecutive cases of newly-diagnosed APL. Five patients died at presentation due to disease complications. Arsenic-induction cohort. 62 newly-diagnosed patients (24 men, 38 women) at a median age of 52 (22-85) years, 36% having high-risk features, consented to and received oral-As2O3 induction. Complete remission (CR) rate was 100%. After a median of 29 (5-69) months, there were no relapses, so that conventional risks (age, leucocyte and platelet counts, FLT3 mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) at 3 years were both 100%. There was no leukemia- or treatment-related mortality. The most common non-hematologic AE was hepatotoxicity, presenting as transaminitis in all cases (grade 1/2, N=19, 30.6%; grade 3/4, N=16, 25.8%). Hyperbilirubinemia did not occur. In the sixteen cases with grade 3/4 transaminitis, oral-As2O3 was temporarily withheld for a median of 2 (1-5) days. With improvement in transaminases, oral-As2O3 was successfully re-administered without recurrence of transaminitis. Three patients developed QTc prolongation to a median maximum of 490 (480-496) ms. It was transient and self-limiting without need for oral-As2O3 dose interruption. Arrhythmias and heart failure were not observed. Headache, nausea and vomiting were other minor and less common AEs, which responded to symptomatic treatment. Non-arsenic-induction cohort. A contemporaneous cohort of 37 newly-diagnosed patients (15 men, 22 women; median age: 51, 23-78 years), 46% having high-risk features, did not consent to oral-As2O3 induction, and received similar induction (without oral-As2O3) and consolidation. CR rate was 100%. Most of them (89%) then received oral-As2O3 maintenance. After a median of 44 (6-69) months, there were three relapses (8%), all achieving remission again with oral-As2O3-containing salvage regimens. Arsenic induction versus non-arsenic induction. To define the role of oral-As2O3 during induction, we selected patients from the arsenic-induction cohort, who received daunorubicin induction, daunorubicin/cytarabine consolidation and AAA maintenance (N=50), and compared them with patients from the non-arsenic-induction cohort, who received the same induction, consolidation and AAA maintenance (N=32). The 5-year OS was comparable (arsenic-induction subgroup, 100% versus non-arsenic-induction subgroup, 96.8%; P=0.25). However, the 5-year LFS of the arsenic-induction subgroup was significantly superior to that of the non-arsenic-induction subgroup (100% versus 89.7%, P=0.04). Conclusion In conclusion, oral-As2O3 induction for newly-diagnosed APL was safe and reduced relapses. Disclosures No relevant conflicts of interest to declare.

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The Impact of Hyperglycemia on Risk of Severe Infections during Early Period of Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma

BioMed Research International ◽

10.1155/2014/413149 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Sung-Hoon Jung ◽

Hee-Chang Jang ◽

Seung-Shin Lee ◽

Jae-Sook Ahn ◽

Deok-Hwan Yang ◽

...

Keyword(s):

Multiple Myeloma ◽

Induction Therapy ◽

Performance Status ◽

Univariate Analysis ◽

Elevated Serum ◽

Poor Performance ◽

Poor Performance Status ◽

Newly Diagnosed ◽

Serious Infections ◽

The Impact

The association between hyperglycemia and infections during induction chemotherapy has been reported in a number of hematologic disorders. This retrospective study evaluated the incidence of hyperglycemia during induction therapy in 155 patients with newly diagnosed multiple myeloma (MM) and its effect on serious infections during the first 60 days of induction. A total of 20 (12.9%) patients developed overt hyperglycemia (≥200 mg/dL) during induction therapy. Serious infections occurred in 28 (18.1%) of 155 patients and infection-related mortality within 2 months after treatment was 0.6% (1 patient). In a univariate analysis, overt hyperglycemia, poor performance status (≥2), International Staging System III, lymphopenia (<500/μL), and elevated serum creatinine (≥2 mg/dL) were found to be associated with serious infections. In multivariate analysis, only overt hyperglycemia (HR 7.846, 95% CI 2.512–24.503,P<0.001) and poor performance status (HR 5.801, 95% CI 1.974–17.050,P=0.001) remained significant. In conclusion, this study demonstrated an association between hyperglycemia and serious infections during induction therapy in patients with MM.

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Evaluation of a Standardized Geriatric Assessment at Diagnosis in a Prospective Cohort of Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2018-99-116400 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2671-2671 ◽

Cited By ~ 1

Author(s):

Colombe Saillard ◽

Frederique Rousseau ◽

Maud Cecile ◽

Cecile Braticevic ◽

Anne Etienne ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Elderly Patients ◽

Geriatric Assessment ◽

Prospective Cohort ◽

Myeloid Leukemia ◽

Global Evaluation ◽

Intensive Chemotherapy ◽

Newly Diagnosed ◽

The Impact

Abstract Introduction: Acute myeloid leukemia (AML) in the elderly is a therapeutic challenge, and global evaluation of comorbidity, performance status, fitness and frailty is crucial for therapeutic decision of treatment intensity. Accurately predicting risks and benefits of available therapies is particularly difficult, as it relies on subjective criteria, no geriatric scores being validated so far. The aim of this study was to evaluate the impact of a standardized geriatric assessment at diagnosis in a prospective cohort of newly diagnosed AML in elderly patients, and to investigate correlations between geriatric scores and overall survival. Methods: All patients aged ≥ 70 years with newly diagnosed AML were prospectively included in this cohort. They all benefited from an exhaustive geriatric assessment in addition to standard AML workup, including ADL, IADL, ECOG, comorbidities, nutritional status (assessed by BMI and mini-MNA), cognitive impairment (mini-COG, mini-GDS), quality of life (QLQ-C30), functional scales (physical, role, emotional, cognitive and social functioning), symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and frailty criteria (physical activity, energy visual scale, mobility, nutrition). Patients were treated according to international guidelines, with intensive chemotherapy, hypomethylating agents, subcutaneous low-dose cytarabine, palliative oral chemotherapy or best supportive care only, according to physician choice. The impact of geriatric scores on 6-months overall survival was analyzed. Results: Between 2010 and 2015, 94 patients were enrolled, including 61.7% of males and 38.3% of females. Median age was 75.5 years (70-96). Initial median leucocytes, neutrophils, hemoglobin, and platelets counts were respectively 4.7 G/L (0.4-174), 1.3 G/L (0.1-5.4), 9.3 g/dL (5.3-13.2), 51 G/L (5-520). Median bone marrow blasts percentage was 55% (20-96). Cytogenetics was favorable, intermediate and adverse in 18%, 62% and 20% respectively. Intensive chemotherapy was chosen in 57.4% of patients, and low intensity or palliative approach in 42.6% of patients. Patients spent a median of 30.5 days in hospital (0-119), received a median of 12 (0-44) red blood cells units and 2 (0-33) platelets units. Global geriatric assessment of patients is reported in Table 1. By univariate analysis, prognostic factors associated with a reduced survival were high dementia risk (HR=3.63, 95% CI=1.4-9.3, p=0.004), high ECOG score (HR=2.1, 95% CI=1.1-4, p=0.02) and high risk of denutrition (HR=3.43, 95% CI=1.33-8.9, p=0.007), while intensive chemotherapy was associated with a better outcome (HR=0.45, 95% CI=0.2-0.9, p=0.014). Multivariate analysis identified high risk of denutrition as independently associated with reduced survival (HR=3.08, 95% CI=1.17-8.11, p=0.02). Intensive chemotherapy treatment tended to impact prognosis but was not statistically significant (HR=0.54, 95% CI=0.27-1.01, p=0.08). Conclusions: In a prospective cohort of newly diagnosed AML elderly patients, an exhaustive standardized geriatric assessment at diagnosis identified high risk patients for mortality. The most relevant prognostic factor was nutritional status, which correlated with overall survival. Other geriatric scores and scales did not impact prognosis, which highlights the difficulty of global evaluation in this population. Patients treated with intensive chemotherapy tended to have a better outcome. Disclosures No relevant conflicts of interest to declare.

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Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis

Cancers ◽

10.3390/cancers11111735 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1735 ◽

Cited By ~ 1

Author(s):

Bonello ◽

Pulini ◽

Ballanti ◽

Gentile ◽

Spada ◽

...

Keyword(s):

Overall Survival ◽

Progression Free Survival ◽

Pooled Analysis ◽

Phase Iii ◽

Newly Diagnosed ◽

Two Phase ◽

Free Survival ◽

Phase Iii Trials ◽

Grade 3 ◽

The Impact

: We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival (73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%, p < 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage.

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