Quantitative Cross-Sectional Analyses of Quality-of-Life Outcomes Related to Race, Sex, Age, and Clinical Stage Among Multiple Myeloma Patients at an Urban Center

Abstract Introduction. Multiple myeloma (MM) patients suffer from disease symptoms and impact on quality of life (QoL) - a patient's sense of enjoyment, well-being, and ability to carry out activities of daily living. Reports on QoL in MM have focused on clinical trials that usually involve younger patients with adequate performance status (PS), mostly Caucasians. The median age of MM onset is 69 years; advanced age is associated with multiple comorbidities and deteriorating PS. Blacks have twice the incidence of MM compared to Caucasians; they also have a higher risk of dying due to poor healthcare utilization. Here, we explored the multifactorial nature of race, sex, age, and clinical stage in patient reported QoL outcomes using quantitative cross-sectional analyses from a single center in urban setting. Methods . Participants with a diagnosis of plasma cell disorders at various stages: MGUS, smoldering myeloma (SMM), or MM (newly diagnosed, maintenance, relapsed/refractory) were sequentially enrolled for a one-time measurement of QOL outcomes. Consent and study questionnaire were conducted verbally. Participants simply responded 'yes' or 'no' to nine question prompts outlined in Table 1, followed by verbal reasoning which was transcribed by the interviewer. The questionnaire included three main domains of QoL assessment based on existing literature review and feedback with our patient population. The first is physical symptoms and function (disease-related symptoms, treatment-related adverse events, sexual health and satisfaction with care), the second is mental health (depression, spirituality), and the third is social impact (financial burden, family support). Data were analyzed using chi-square test of independence. Participants will be re-approached for a second interview to determine changes to impact across the same QoL variables over time. The questionnaires validated within the current study will be used for a longitudinal cohort study to investigate whether a greater degradation is observed in one or more QoL domains during a specific time-point of MM disease course. Results. A total of 100 patients (males n=52) were enrolled. Median age was 64 years (IQR 55 - 68); 59 were Caucasian, 34 were Black, and 7 from other racial groups. At the time of interview: 7 were newly diagnosed or receiving induction therapy, 25 were undergoing stem cell transplant (SCT), 22 were on maintenance therapy, 33 were relapsed on salvage therapy, and 13 on no therapy (MGUS/SMM). Regardless of race, age, or sex, patients on therapy felt their QOL was impacted by fatigue (67%), and myeloma symptoms (65%). Black participants reported more fatigue as an impact on their QoL compared to other racial groups, p = .009. Women reported more impact from MM on sexual intimacy, p = .04, and impact from financial burden than male participants, p = .03. Younger patients <60 years old (n=38) reported more impact from treatment-related adverse events, p = .004, disease-related symptoms, p = .02, and dissatisfaction with information received about their disease and/or treatment, p = .004, compared to patients aged >60 years. Not surprisingly, patients with active MM (n=87); newly diagnosed on therapy, those undergoing SCT, or on maintenance, and relapsed disease) reported more MM symptoms p = <.001, and suffered from more fatigue, p = <.02, with higher impact on QoL compared to those with early-stage plasma cell disorders (MGUS, SMM). However, early-stage patients felt more dissatisfaction with information received and uncertainty about what to expect, p = <.001, compared to MM patients receiving therapy. Interestingly, there were no age, sex, race, or clinical stage dependent effects observed from SCT experience, spirituality or religion, and dissatisfaction with cancer care. Conclusions. Patients <60 years were impacted more by disease-related symptoms, treatment-related adverse events, in comparison to patients >60 years. Women felt their QoL was impacted by MM's affect on sexual intimacy and resulting financial burden in comparison to men. Black participants felt greater impact from fatigue in comparison to Caucasian and other races. Active MM patients on treatment were more impacted by disease-related symptoms and fatigue compared to early-stage patients. MGUS/SMM patients not on therapy were more impacted by dissatisfaction of information received compared to patients receiving treatment at time of data collection. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

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A Phase 2 Trial of Imatinib Mesylate As Maintenance Therapy for Patients with Newly Diagnosed C-Kit Positive Acute Myeloid Leukemia (AML)

Blood ◽

10.1182/blood.v120.21.3597.3597 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3597-3597

Author(s):

Anjali Advani ◽

Brenda Cooper ◽

Olumuyiwa Sowunmi ◽

Paul Elson ◽

Francis Ali-Osman ◽

...

Keyword(s):

Gene Expression ◽

Adverse Events ◽

Imatinib Mesylate ◽

Research Funding ◽

Dose Intensity ◽

Multi Drug Resistance ◽

Optimum Dose ◽

High Dose ◽

Newly Diagnosed ◽

Fluorescent Intensity

Abstract Abstract 3597 The c-kit (CD117) receptor is expressed on > 10% blasts in 64% of de novo AMLs and mediates proliferation and anti-apoptotic effects. High c-kit levels correlate with a shorter time to relapse and decreased overall survival (OS). Imatinib mesylate (IM), a c-kit inhibitor, has activity against relapsed/refractory AML. The primary objective of this study was to determine whether adding maintenance IM for 1 yr after completion of standard induction (IT) and post-remission therapy (PRT) in patients (pts) with newly diagnosed c-kit+ AML improves relapse-free survival (RFS) compared to historical controls. Secondary objectives included: (1) assessing the feasibility of this approach; (2) evaluating outcomes based on c-kit expression (c-kit mean fluorescent intensity [MFI]); (3) determining whether c-kit expression correlates with AF1q gene and/or multi-drug resistance (MDR) gene expression. Methods: Pts were treated at Cleveland Clinic, Duke, Roswell Park, and University Hospitals of Cleveland from 2008 to 2012. IM was supplied by Novartis. Eligibility criteria included: pts age ≥ 18 yrs, AML in first complete remission (CR1), ≥ 20% c-kit+ blasts at diagnosis (dx), ECOG performance status 0–2. Cytogenetics (CG) were classified by CALGB 8461. Pts must have received IT (7+3 [continuous infusion cytarabine (C) and an anthracycline] or ADE [C, daunorubicin, etoposide]) and PRT (≥ 1 course for pts > 60 yrs; ≥ 2 courses for pts < 60 yrs). CR status was confirmed by bone marrow analysis prior to study enrollment. MDR expression was analyzed by immunohistochemistry on diagnostic samples (n=19); AF1q gene expression was analyzed by RT-PCR on RNA from available diagnostic pt samples (n=9) as previously described (Tse et al. Blood 2004; 104: 3058–63). C-kit MFI was calculated as the mean channel number (MCN) of the blasts/MCN autofluorescence using a CD45/orthogonal light scatter gate to isolate blasts. All pts received IM 600 mg/day for 12 months (mos) unless they experienced toxicity or disease progression. Dose modifications were made for Grades 2–4 non-hematologic toxicity and Grades 3–4 neutropenia and thrombocytopenia. Pts remaining off IM for > 4 wks were removed from treatment. Cumulative dose intensity was defined as the proportion of the total optimum dose administered over time. Results: Thirty-three pts were enrolled, with 32 pts having complete data. The median age was 54 yrs (range 19–81), median WBC at dx 22.13 K/μL (1.55–98.44), median peripheral blood blasts at dx 23.6% (range 0–85), and 44% were male. CG risk included: 47% (15) good, 31% (10) intermediate, and 22% (7) poor. The median c-kit % was 79.9, and median c-kit MFI 39.8 (range 6.5–120.1). Median AF1q expression was 9.59 (range 1.83–161.8.5). Eighty-four percent of pts had moderate or high levels of MDR expression (GSTP1, MDR1, LRP1, and/or MRP1); almost half (47%) had high expression. The majority of pts (74%, n=20) received PRT with high dose C (3 g/m2/dose × 6 doses/cycle). Pts received IM for a median of 4.0 mos (range 0.1–12.2), and the median daily dose was 600 mg. Twelve pts (38%) were dose reduced to 400 mg. Forty-five percent (13/29) of pts experienced grade 3 reactions possibly related to treatment, with the majority (31%) being myelosuppression. The most commonly reported adverse events were Grade 1/2 nausea and vomiting (72%), edema (59%), and fatigue (41%). Twelve pts (38%) discontinued treatment for adverse events. The median RFS survival is 18.8 mos, with a median follow-up of 19.1 mos (range 6.4–37.2). Estimated 2-yr OS is 62% ± 10%. Predictors of RFS included: age, WBC at dx, % peripheral blasts at dx, and CG risk. Dose intensity of IM did not correlate with outcome. AF1q and MDR expression did not correlate with c-kit MFI; although the number of pts with AF1q data was small. Of note, neither c-kit MFI nor AF1q expression were prognostic in this subset of pts treated with IM. With the exception of LRP1 expression (p=0.03), there was no correlation of MDR expression with RFS. Conclusions: Previous studies have demonstrated that c-kit MFI > 20.3 is an independent adverse prognostic factor for RFS and OS (median RFS 10.7 months). Considering the high c-kit MFI of pts in this study, the outcomes using IM maintenance are encouraging, and suggest that further study of this approach is warranted. Given the toxicities observed, reducing the dose of IM to 400 mg in the maintenance setting may be better tolerated. Disclosures: Advani: Novartis: Research Funding. Rizzieri:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kalaycio:Novartis: Research Funding, Speakers Bureau. Maciejewski:Novartis: Research Funding.

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PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome

Blood ◽

10.1182/blood.v126.23.176.176 ◽

2015 ◽

Vol 126 (23) ◽

pp. 176-176

Author(s):

Margaretha GM Roemer ◽

Ranjana H Advani ◽

Azra H. Ligon ◽

Yasodha Natkunam ◽

Robert A Redd ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Early Stage ◽

Prognostic Significance ◽

Genetic Alterations ◽

Genetic Alteration ◽

Newly Diagnosed ◽

Advisory Committees ◽

Therapy Regimen ◽

Clinical Risk

Abstract Introduction. Classical Hodgkin Lymphomas (cHL) include small numbers of malignant Reed-Sternberg (RS) cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction via JAK2-STAT signaling. PD-1 ligands engage the PD-1 receptor on T-cells and induce PD-1 signaling and T-cell exhaustion. Tumor cells expressing PD-1 ligands on their surface utilize the PD-1 pathway to evade an effective immune response. In recent pilot studies, PD-1 blockade was associated with high response rates and durable remissions in relapsed/refractory cHL. The unique composition of cHL limits its analysis with high throughput genomic assays. Therefore, the precise incidence, nature and prognostic significance of PD-L1 and PD-L2 alterations in cHL remain undefined. Herein, we utilize a recently developed fluorescence in situ hybridization (FISH) assay to characterize 9p24.1/PD-L1/PD-L2 alterations in a cohort of 108 newly diagnosed cHL patients (pts) who were uniformly treated with StanfordV (a combined modality therapy regimen) and have longterm followup. Methods. Pts were characterized as Ann Arbor early stage I/II favorable risk (ES-F), early stage unfavorable risk (bulk ≥ 10cm or ≥ .33 mediastinal dimension and/or B symptoms) (ES-U) or advanced stage III/IV (AS). ES-F pts received 8 weeks of Stanford V and 30 Gy involved field radiation (IFR); ES-U and AS pts received 12 weeks of Stanford V and 36 Gy IFR to initial sites > 5 cm. FISH was performed on formalin-fixed paraffin-embedded diagnostic biopsy specimens using bacterial artificial chromosome probes which covered CD274/PD-L1 (labeled with spectrum orange) and PDCD1LG2/PD-L2 (labeled with spectrum green) and a control centromeric probe (spectrum aqua-labeled CEP9, from 9p11-q11). Malignant RS cells were identified by their nuclear morphologic features and 50 RS cells/case were analyzed. Nuclei with a target:control probe ratio of at least 3:1 were defined as amplified (amp), those with a probe ratio of more than 1:1 but less than 3:1 were classified as relative copy gain, and those with a probe ratio of 1:1 but more than 2 copies of each probe were defined as polysomic for chromosome 9p. In each case, the percent and magnitude of disomy, polysomy, copy gain and amp were noted. In accordance with clinically approved diagnostic criteria, cases were classified by the highest observed level of 9p24.1 alteration. Specifically, cases with polysomy lacked copy gain or amp and cases with copy gain lacked amp. Immunohistochemical staining for PD-L1/PAX5 was performed as previously described and PD-L1 expression in PAX5 dim+ malignant RS cells and PAX5- infiltrating normal cells was assessed separately. Results. Almost all newly diagnosed cHL pts in this series had concordant alterations of the PD-L1 and PD-L2 loci; disomy was found in only 1% (1/108), polysomy in 5% (5/108), copy gain in 56% (61/108) and amp in 36% (39/108) of study pts. There was a correlation between intensity of PD-L1 protein expression and relative genetic alterations in this series. Two additional pts had translocations of PD-L1 or PD-L2 (2%, 2/108). We next assessed the association between specific types of PD-L1/PD-L2 alterations, clinical risk factors and outcome. Overall, the progression-free survival (PFS) was significantly lower for AS pts compared to ES-F/U pts (p=0.017). A model of PFS for the cHL pts by genetic alteration indicated that PFS was also significantly lower for pts with amp (p=0.02). Consistent with these findings, the incidence of 9p24.1 amp increased by clinical risk group: ES-F, 24%; ES-U, 34%; and AS, 50% (p=0.024, Kruskal-Wallis test). Therefore, we fit a full model of clinical and genetic factors including B-symptoms, bulk, stage and amp. Despite the association of amp with increased clinical risk groups, the genetic alteration further delineated PFS in the multivariate model (p=0.075). Conclusions. PD-L1/PD-L2 alterations are a defining feature of cHL with rare polysomy and more frequent copy gain and amp. There is an increased incidence of amp in pts with AS disease and a highly significant association of PD-L1/PD-L2 amp with PFS. These findings underscore the importance of genetically defined PD-1 mediated immune evasion in cHL and provide a rationale for the efficacy of PD-1 blockade in this disease. Disclosures Rodig: Perkin Elmer: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding. Shipp:BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Gilead: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees.

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Bortezomib-Pomalidomide-Dexamethasone (VPD) As Novel Induction Therapy in Newly-Diagnosed Multiple Myeloma: Early Safety Data from an Ongoing Single Arm Phase-II Investigator-Initiated Clinical Trial (PRIME Study)

Blood ◽

10.1182/blood-2021-151718 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2752-2752

Author(s):

Vivek S Radhakrishnan ◽

Naveed Tamboli ◽

Shreya Das ◽

Jeevan Kumar Garg ◽

Arijit Nag ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Board Of Directors ◽

Phase Ii ◽

Research Funding ◽

Safety Data ◽

Bone Lesions ◽

Newly Diagnosed ◽

Advisory Committees ◽

Tertiary Center

Abstract Introduction: Pomalidomide is a third-generation immunomodulatory drug approved for relapsed and/or refractory Multiple Myeloma (RRMM). In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone demonstrated superior efficacy in patients with RRMM. PRIME study (CTRI/2019/10/021618) is testing this combination in Newly Diagnosed Multiple Myeloma (NDMM) Aim: To determine safety of Pomalidomide in combination with Bortezomib and dexamethasone (VPD) in NDMM Study design: A prospective, single arm, phase II study from a tertiary center. Both transplant eligible and ineligible patients with NDMM aged between 18-70 years are being recruited in the study. Patients with Plasma cell leukemia, POEMS and amyloidosis were excluded. The regimen consists of weekly Bortezomib 1.3mg/sq.m (subcutaneous), Tab. Pomalidomide 2-4mg once daily for 21days, and Tab Dexamethasone 20mg twice weekly, with the cycle repeating every 28 days, 9-12 cycles. Here we report the adverse events (AE) by NCI CTCAE v5.0, upon recruiting 26 patients, as predetermined in the study. Results: Of the proposed 45-50 patients, 26 patients were enrolled in the study between April 2020 to May 2021 and 23 (88.4%) have completed 4 cycles of VPD. The median age is 55years (18-70), and gender ratio 1:1. At disease presentation, bone lesions were the commonest (96.2%, n=25), IMWG high risk cytogenetics were seen in 42.4% (n=11), RISS-2 in 69.3% (n=18), IgG kappa paraproteinemia in 54% (n=14) patients and ECOG performance score 2-3 in 57.6%(n=15). Ten (38.5%) patients have completed 9 cycles, and 3 underwent auto-transplant (between Cycle 4 & 6). Protocol adherence was 96.1% (25/26 patients). Table-1 shows drug-induced toxicity, hematological toxicities were the commonest. Two patients withdrew consent in view of bortezomib-induced peripheral neuropathy. Serious adverse events (SAE) were reported in 9 (34.6%) patients and were considered unrelated to the regimen by the safety committee (PSVT=1, Bony pain=2, dyspnea=1, pneumonia=1, constipation=1, diarrhea=1, hypotension=1) and one death due to SARS-CoV2 pneumonia. Treatment delays of 2 weeks in 4 patients (SARS-CoV2 = 3, Syncope = 1) After 4 cycles (n=23), 6 (26%) patients were in stringent Complete Response (sCR), 17(74%) in Very Good partial response (VGPR) and 13 (56.5%) are Measurable Residual Disease (MRD) negative. Of 10 patients who completed cycle 9, 9 were MRD negative and 1 showed disease progression. Conclusion: Safety data from the PRIME study demonstrates that VPD regimen has a favorable tolerance profile in patients with NDMM. Early efficacy signals are encouraging, and recruitment continues. Figure 1 Figure 1. Disclosures Radhakrishnan: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees; Emcure Pharmaceuticals: Research Funding; Intas Pharmaceuticals: Research Funding; Janssen India: Honoraria; NATCO Pharmaceuticals: Research Funding; Novartis India: Membership on an entity's Board of Directors or advisory committees; Roche India: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca India: Honoraria, Speakers Bureau; Bristol-Myers-Squibb India: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cipla Pharmaceuticals India: Research Funding; Aurigene: Speakers Bureau. Garg: Dr Reddys Laboratories: Honoraria, Speakers Bureau. Nair: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intas pharmaceuticals: Honoraria, Speakers Bureau; Mylan pharmaceuticals: Honoraria; Novartis India: Honoraria; Fresenius Kabi India: Honoraria; Cipla Pharmaceuticals: Honoraria, Speakers Bureau; Janssen India: Honoraria, Speakers Bureau. Chandy: Janssen: Honoraria; Pfizer: Honoraria; Intas Pharmaceuticals: Research Funding.

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Treatment Patterns, Adverse Events, and Economic Burden in a Privately Insured Population of Newly Diagnosed Patients with Chronic Lymphocytic Leukemia in the United States

Blood ◽

10.1182/blood-2018-99-114735 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3557-3557 ◽

Cited By ~ 1

Author(s):

Shaum Kabadi ◽

Ravi K Goyal ◽

Saurabh P Nagar ◽

James A Kaye ◽

Keith L Davis ◽

...

Keyword(s):

Health Care ◽

Adverse Events ◽

Systemic Therapy ◽

Research Funding ◽

The United States ◽

Treatment Patterns ◽

Newly Diagnosed ◽

The Us ◽

Privately Insured

Abstract Introduction: Contemporary data describing treatment patterns, adverse events (AEs) and outcomes in CLL patients in clinical practice is lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health care resource use (HCRU), and costs in patients with newly diagnosed CLL. Methods: Using a nationally representative population of privately insured patients in the US, adult patients with CLL were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL-directed treatment. Treatment patterns up to 4 lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per-patient monthly HCRU and costs were assessed overall and by number of unique AEs. Results: Of all patients meeting the selection criteria (n=7,639; median age, 66 years), 18% (n=1,379) received a systemic therapy during study follow-up. The most common systemic therapy regimens, regardless of therapy line, were bendamustine/rituximab (BR) (32%), rituximab monotherapy (24% [including maintenance]), ibrutinib monotherapy (15%), and fludarabine/cyclophosphamide/ rituximab (FCR) (14%). Of these, BR was the most common LOT-1 regimen (28.1%), while ibrutinib was the most common regimen in LOT-2 (20.8%) and in LOT-3 (25.5%). Use of idelalisib was limited to 1.6% of all patients receiving systemic therapy; however, an increasing trend was observed as patients moved from first to fourth LOT (<1% in LOT-1, 3.1% in LOT-2, 4.7% in LOT-3, and 8.6% in LOT-4). AEs identified during the most common treatments for CLL are presented by treatment regimen in Table 1. The mean monthly all-cause and CLL-related costs, among patients treated with a systemic therapy, were $7,943 (SD=$15,757) and $5,185 (SD=$9,935), respectively. Figure 1 depicts mean monthly costs by care setting and number of AEs, among all patients. Mean (SD) monthly all-cause costs during the post-index date follow-up were $905 ($1,865) among those with no AEs, $1,655 ($5,364) among those with 1-2 AEs, $2,883 ($8,483) among those with 3-5 AEs, and $6,032 ($13,290) among those with ≥6 AEs. Conclusions: This population-based study yielded recent real-world evidence on treatment patterns, AEs, HCRU, and costs in patients enrolled in health plans in the US. Immunochemotherapy, particularly BR, remained the preferred frontline therapy for CLL, whereas ibrutinib was the preferred therapy in LOT-2 and LOT-3, during the study period. This study demonstrates that the AE burden associated with current treatment alternatives for CLL is substantial, and the management of AEs occurring during treatments may have a significant impact on the overall health care costs. Disclosures Kabadi: AstraZeneca: Employment. Goyal:RTI Health Solutions: Employment, Research Funding. Nagar:RTI Health Solutions: Employment, Research Funding. Kaye:RTI Health Solutions: Employment, Research Funding. Davis:RTI Health Solutions: Employment, Research Funding. Mato:Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Sunesis: Honoraria, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Honoraria; Acerta: Research Funding; Prime Oncology: Speakers Bureau; Regeneron: Research Funding.

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Cost-Effectiveness of Zoledronic Acid Versus Clodronate In Patients with Multiple Myeloma From a Canadian Healthcare System Perspective.

Blood ◽

10.1182/blood.v116.21.3812.3812 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3812-3812

Author(s):

Thomas E. Delea ◽

Khalid El Ougari ◽

Jason Rotter ◽

Alice Wang ◽

Satyin Kaura ◽

...

Keyword(s):

Multiple Myeloma ◽

Cost Effectiveness ◽

Zoledronic Acid ◽

Adverse Events ◽

Research Funding ◽

Proportional Hazards ◽

Survival Function ◽

Newly Diagnosed ◽

Kaplan Meier ◽

Skeletal Related Events

Abstract Abstract 3812 Background: The Medical Research Council (MRC) Myeloma IX study compared the intravenous (IV) bisphosphonate, zoledronic acid (ZOL) 4 mg q 3–4 wk with the oral bisphosphonate, clodronate (CLO) 1,600 mg/d PO, in 1,970 patients with newly-diagnosed multiple myeloma (MM). After a median follow-up of 3.7 yrs (max. follow-up 6 years), ZOL prolonged OS (median 50.0 vs. 44.5 months; HR=0.842; p=0.0118), increased PFS (median 19.5 vs. 17.5 months; HR=0.883; P=0.0179), and reduced the incidence of skeletal related events (SREs) (27.0% vs. 35.3%; HR=0.74; P=0.0004) compared with CLO. The incidence of acute renal failure (ARF) was similar in the two groups (5.8% vs. 6.1% with ZOL vs. CLO). The incidence of osteonecrosis of the jaw (ONJ) was 3.5% with ZOL and 0.3% with CLO. The objective of this study was to evaluate the cost-effectiveness of ZOL vs. CLO in patients with newly-diagnosed MM based on the reported findings of the MRC Myeloma IX trial. Methods: An economic model was used to project PFS, OS, the incidence of SREs (vertebral and other fractures, radiotherapy, bone surgery, and spinal cord compression) and adverse events (ARF, ONF, thromboembolism, and infection) as well as expected lifetime healthcare costs for patients with newly diagnosed MM who are alternatively assumed to received bishphosphonate therapy with ZOL or CLO. Cost-effectiveness was expressed in terms of the incremental cost per quality-adjusted life-year (QALY) gained with ZOL vs. CLO. Clinical data were based on reported results of the MRC Myeloma IX trial. OS for CLO and ZOL up to 5 years were based on reported Kaplan-Meier survival curves. For CLO, OS after 5 years was projected based on a Weibull survival function fitted to the reported Kaplan-Meier curve. For ZOL, OS after 5 years was obtained by applying the estimated HR for ZOL vs. CLO to the estimated Weibull survival function for CLO. PFS for CLO and ZOL were estimated based on reported medians and the HR for ZOL vs. CLO, assuming proportional hazards Weibull distributions (Kaplan-Meier curves were not reported for PFS). Costs and utility values were obtained from published sources. Costs were in 2009/10 Canadian dollars. Costs and QALY were discounted at 5% annually. Results: Expected lifetime costs of bisphosphonate therapy (including administration and monitoring costs) were $11,967 greater with ZOL vs. CLO ($14,267 vs. $2,301). Expected costs of SREs were reduced by $720 with ZOL ($4,152 vs. $4,872). Expected costs of adverse events were increased by $663 with ZOL ($3,225 vs. $2,562). Expected total lifetime costs were increased by $11,878 ($30,103 vs. $18,225). Life expectancy (undiscounted) was increased by 0.83 years with ZOL (6.43 vs. 5.60). QALYs gained from increased PFS and OS with ZOL vs. CLO were 0.56. QALYs gained from SREs averted with ZOL vs. CLO were <0.01. QALYs lost due to adverse events (predominantly ONJ) were 0.02. Total QALYs gained with ZOL vs. CLO (undiscounted) were 0.56 (4.43 vs. 3.87). On a discounted basis, total QALYs gained were 0.37 (3.51 vs. 3.14). Cost effectiveness with ZOL vs. CLO was $32,210 per QALY gained. In probabilistic sensitivity analyses, the probability that ZOL is preferred to CLO was 85% with a cost-effectiveness threshold of $50,000 per QALY and a 98% with a threshold of $100,000 per QALY. Cost-effectiveness was $43,487 per QALY gained if benefits of ZOL on OS are conservatively assumed to persist for 6 years only (i.e., HR for OS=1.0 after 6 years). Results were sensitive to methods used to estimate PFS and OS (i.e., Kaplan Meier or Weibull models, independent or proportional hazards assumption), and the estimated costs and QALYs lost with ONJ. Conclusions. The cost per QALY gained with ZOL vs. CLO in patients with newly-diagnosed MM is below the commonly-accepted threshold of $50,000 per QALY gained. More precise estimates await release of additional results from the MRC Myeloma IX study. Disclosures: Delea: Novartis: Consultancy, Research Funding. Off Label Use: Zoledronic acid for prevention of skeletal related events in patient with multiple myeloma. Ougari:Novartis: Employment. Rotter:Novartis: Consultancy, Research Funding. Wang:Novartis: Consultancy, Research Funding. Kaura:Novartis: Employment. Morgan:Novartis: Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Pharmion: Research Funding; Celgene: Research Funding; Chugai: Research Funding; Ortho Biotech: Research Funding.

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Deferred Treatment Is Associated with Improved Overall Survival in Patients with Newly Diagnosed Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.2717.2717 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2717-2717

Author(s):

Jonathon B. Cohen ◽

Xuesong Han ◽

Xin Hu ◽

Ahmedin Jemal ◽

Elizabeth Ward ◽

...

Keyword(s):

Overall Survival ◽

Mantle Cell Lymphoma ◽

Research Funding ◽

Cell Lymphoma ◽

Early Stage ◽

Cohort Analysis ◽

Newly Diagnosed ◽

Early Stage Disease ◽

Deferred Treatment ◽

Mantle Cell

Abstract Background: Although mantle cell lymphoma (MCL) has traditionally been considered an aggressive lymphoma with shortened survival, the long-term outcomes and initial presentation can be heterogeneous. Martin et al (JCO 2009) reported that 32% of patients with MCL at an academic referral center deferred therapy for at least 3 months, with a median overall survival (OS) of 64 months for patients treated within 90 days of diagnosis and median OS not reached for those who deferred therapy. We used the National Cancer Database (NCDB) to perform a national cohort analysis of the impact of deferred therapy in MCL. Methods: The NCDB is a nationwide oncology outcomes database sponsored by the Commission on Cancer of the American College of Surgeons and the American Cancer Society, capturing nearly 70% of all newly diagnosed cases of cancer in the United States. We included all patients ≥18 years old who received initial treatment for newly diagnosed MCL in 2004-2011. MCL patients were identified by the International Classification of Diseases for Oncology code 9673 and variables of interest were captured using the Facility Oncology Registry Data Standards. Patients were determined to have received deferred therapy if their time to initial treatment was > 90 days. Chi-square tests were used as appropriate to compare baseline characteristics between immediate and deferred treatment groups, and OS was estimated using the Kaplan-Meier method. Log-binomial regression models were developed to identify characteristics associated with deferred treatment and multivariable Cox proportional hazard models were fit to evaluate the relationship between deferred treatment and OS. Results: Of 8209 patients with MCL, 492 (6.1%) received therapy > 90 days from diagnosis with a median time to treatment for this group of 121 days (range 91-1152). Among all patients, 64% were > 60 years of age, 73% were male, 85% were stage III/IV, and 83% had primarily nodal disease. Additional comorbidities were identified in 22% of patients, and 28% of patients presented with B-symptoms at diagnosis. Approximately 1/3 of patients received therapy in a high volume teaching/research institution. Compared to patients treated within 90 days of diagnosis, patients receiving deferred therapy were more likely to have early stage disease (22% vs 15% p<0.0001), extranodal presentation (24% vs 17%, p<0.0001), to be located in the Northeast region (26% vs 20%, p<0.0001), and to be treated at a high volume teaching/research institution (41% vs 33%, p=0.005). Patients treated within 90 days of diagnosis more commonly had B-symptoms (29% vs 16%, p<0.0001). There were no significant differences between the two groups with regard to gender, age, year of diagnosis, socioeconomic status (based on location of residence), or primary payer. When analyzed in a multivariable model, lack of B-symptoms (RR 1.67, 95% CI 1.38-2.03, p < 0.0001) and extra-nodal status (RR 1.24, 95% CI 1.00-1.53, p = 0.0468) were two strong clinical predictors of deferred therapy. Multivariable analysis demonstrated improved OS for patients who received deferred therapy (HR 0.79: 95% CI 0.67-0.93, p = 0.005; See Figure 1). Additional significant predictors of improved OS included age ≤ 60 years (HR 0.60: 95% CI 0.54-0.66, p < 0.0001), early stage disease (HR 0.66: 95% CI 0.59-0.74, p < 0.0001), lack of B-symptoms (HR 0.75: 95% CI 0.70-0.81, p < 0.0001), and lack of comorbidities (HR 0.63: 95% CI 0.58-0.68, p < 0.0001). Non-Hispanic black patients had inferior OS compared to the other racial/ethnic groups. Among patients who deferred therapy, male gender (p=0.046), age ≤ 60 years (p=0.0002) and lack of comorbidities (p<0.0001) were associated with improved OS, while remaining variables including region, stage, race, B-symptoms, and extranodal presentation were not. Discussion: This national cohort analysis supports prior reports that deferred therapy in MCL is safe for a subgroup of patients with MCL. We found that deferred therapy > 90 days was associated with improved OS and that lack of B-symptoms was a strong predictor for deferred therapy. Predictors of improved survival for patients deferring therapy included young age and lack of comorbidities. These data support use of watchful waiting approach for well-selected newly diagnosed MCL patients. Figure 1. Overall survival for newly diagnosed patients with mantle cell lymphoma based on time to initiation of therapy. Figure 1. Overall survival for newly diagnosed patients with mantle cell lymphoma based on time to initiation of therapy. Disclosures Cohen: BMS: Research Funding; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy; Millennium: Consultancy; Celgene: Consultancy; Janssen: Research Funding. Flowers:Infinity Pharmaceuticals: Research Funding; Acerta: Research Funding; Millennium/Takeda: Research Funding; AbbVie: Research Funding; Gilead Sciences: Research Funding; Acerta: Research Funding; Gilead Sciences: Research Funding; Onyx Pharmaceuticals: Research Funding; Janssen: Research Funding; OptumRx: Consultancy; Spectrum: Research Funding; Seattle Genetics: Consultancy; Infinity Pharmaceuticals: Research Funding; Genentech: Research Funding; Millennium/Takeda: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Onyx Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Spectrum: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding; Seattle Genetics: Consultancy; Celegene: Other: Unpaid consultant, Research Funding; OptumRx: Consultancy.

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Lenalidomide Compared to Ixazomib Maintenance in Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2021-151644 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3776-3776

Author(s):

Eunice Lai ◽

Yu Yang Soon ◽

Ainsley Ryan Yan Bin Lee ◽

Shi Yin Wong ◽

Cinnie Yentia Soekojo ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Maintenance Therapy ◽

Research Funding ◽

Meta Analysis ◽

Proteasome Inhibitors ◽

Progression Free Survival ◽

Risk Of Bias ◽

Newly Diagnosed ◽

Maintenance Strategies

Abstract Background Maintenance therapy is considered a standard of care in transplant eligible (TE) and non transplant eligible (NTE) patients with newly diagnosed multiple myeloma (NDMM). While immunomodulators (IMID) and proteasome inhibitors (PI) have been proposed as maintenance therapy options, there are no randomised trials (RCTs) directly comparing these agents in the maintenance setting. The IMID lenalidomide (Len) and the PI ixazomib (Ixa) have been compared against placebo as maintenance strategies in NDMM. We present a network meta-analysis (NMA) of RCTs comparing the efficacy and safety of Len and Ixa maintenance therapies in NDMM. Methods We searched various biomedical databases for eligible studies evaluating Len or Ixa against placebo/ observation as maintenance therapy in patients with NDMM from date of inception through November 2020. The primary outcome was progression-free survival (PFS). Secondary outcomes include overall survival (OS) and adverse events (AE). The Cochrane risk of bias tool version 2.0 was used to assess trial quality. A Bayesian NMA model was used to assess the relative effects of competing treatments on PFS and OS outcomes. Adverse events were assessed using the synthesis without meta-analysis (SWIM) approach due to variability in the toxicity scoring criteria. The GRADE approach was used to rate the certainty of the evidence. This study is registered with PROSPERO, CRD42021226157. Results We identified eight studies including 3229 transplant eligible (TE) and 1689 non transplant eligible (NTE) patients. All studies were judged to have low risk of bias. Len but not Ixa was associated with statistically significant improvement in PFS when compared to placebo in TE (Len: Hazard Ratio (HR) 0.46, 95% Credible Interval (CrI) 0.35-0.56, high certainty; Ixa: HR 0.72, 95% CrI 0.46-1.13, moderate certainty) and NTE (Len: HR 0.46, 95% CrI 0.29-0.75, high certainty; Ixa: HR 0.69, 95% CrI 0.43-1.18, moderate certainty). Bayesian modelling demonstrated a 97% and 93% probability that Len resulted in superior PFS compared to Ixa in TE and NTE patients respectively. Both Len and Ixa were not associated with statistically significant improvement in OS compared to placebo in TE and NTE patients. There was no significant effect modification on the effect of Len vs placebo and Ixa vs placebo by cytogenetics status, use of proteasome inhibitors for induction or duration of maintenance therapies for PFS and/or OS outcomes. Len were judged to have a higher incidence of second malignancies and grade 3 or 4 neutropenia than Ixa while Ixa was judged to have a higher incidence of thrombocytopenia than Len. Conclusions Maintenance therapy with Len may provide a larger PFS benefit than Ixa regardless of type of induction therapy and cytogenetic risk in patients with NDDM. The differing toxicity profile of these agents is also an important consideration for treatment decisions. RCTs directly comparing these maintenance strategies are warranted. Figure 1 Figure 1. Disclosures Ooi: Jansen: Honoraria; Teva Pharmaceuticals: Honoraria; GSK: Honoraria; Abbvie: Honoraria; Amgen: Honoraria. Chng: Sanofi: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Johnson and Johnson: Honoraria, Research Funding; Pfizer: Honoraria.

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COMPARISON OF CYTHOCROME P450 FAMILY 2 SUBFAMILY A POLYPEPTYDE 6 (CYP2A6) GENE POLYMORPHISM PROPORTION ON EARLY AND ADVANCED STAGE OF UNDIFFERENTIATED TYPE NASOPHARYNGEAL CARCINOMA IN BALINESE

INTERNATIONAL JOURNAL OF NASOPHARYNGEAL CARCINOMA (IJNPC) ◽

10.32734/ijnpc.v1i03.2066 ◽

2019 ◽

Vol 1 (03) ◽

pp. 97-99

Author(s):

I Gde Ardika Nuaba ◽

Komang Andi Dwi Saputra ◽

I Ketut Suanda ◽

I Gusti Ayu Trisna Dewi

Keyword(s):

Nasopharyngeal Carcinoma ◽

Gene Polymorphism ◽

Early Stage ◽

Clinical Stage ◽

P Value ◽

Advanced Stage ◽

Cross Sectional ◽

Pcr Rflp ◽

Undifferentiated Type ◽

Cyp2a6 Gene

Introduction Nasopharyngeal carcinoma (NPC) is a malignancy derived from epithelial cells lining the nasopharynx. The etiology of nasopharyngeal carcinoma is multifactorial. One of the risk factors is CYP2A6 gene polymorphism which causes nitrosamines are not metabolized, leading to DNA change that could trigger cancer. Objectives The purpose of this study is to know the association of CYP2A6 gene polymorphism and clinical stage of undifferentiated type of NPC Material and Method This is a cross sectional analytic study. The sample in this study were 80 nasopharyngeal carcinoma patients whose treated in ENT-HN department of Sanglah General Hospital between 2017 - 2018. The collected data consist of subject’s characteristic and CYP2A6 gene polymorphisms identified by the PCR-RFLP technique. Results The probability of CYP2A6 gene polymorphism in the undifferentiated type of NPC in the Balinese tribe is 3.125 times greater in advanced stage than early stage. Based on multivariate analysis, there was a statistically significant association between CYP2A6 gene polymorphism and clinical stage of undifferentiated type NPC in Balinese with p value = 0,0048 (p < 0,05). Conclusion There is association between CYP2A6 gene polymorphism and clinical stage of undifferentiated type NPC in Balinese tribe.

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Quality-Adjusted Survival for Low-Dose Cytarabine (LDAC) Versus Glasdegib+LDAC Among Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Not Candidates for Intensive Chemotherapy: A Q-TWiST Analysis

Blood ◽

10.1182/blood-2019-126672 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2610-2610 ◽

Cited By ~ 1

Author(s):

Youngmin Kwon ◽

Timothy J Bell ◽

Caitlyn Solem ◽

Joseph C Cappelleri ◽

Courtney Johnson ◽

...

Keyword(s):

Adverse Events ◽

Myeloid Leukemia ◽

Research Funding ◽

Newly Diagnosed ◽

Employment Equity ◽

Equity Ownership ◽

Relative Gains ◽

Mean Time ◽

Low Dose Cytarabine

Introduction: The efficacy and safety of glasdegib (a selective oral inhibitor of hedgehog signaling pathway) in combination with low-dose cytarabine (LDAC) was evaluated in a randomized, phase 2 trial of newly diagnosed acute myeloid leukemia (AML) patients (BRIGHT AML 1003; NCT01546038). Patients receiving glasdegib+LDAC experienced statistically significant and meaningful gains in overall survival (OS) compared with patients receiving LDAC alone (median OS [95% CI]): 8.3 months [4.7-12.2] vs 4.3 months [1.9-5.7]). This analysis examined whether quality-adjusted survival improvements were similarly observed using a quality-adjusted time without symptoms of disease progression or toxicities (Q-TWiST) approach to evaluate possible trade-offs between time with adverse events (toxicities), time in relapse/progression (i.e., with symptoms of disease), and 'good' survival (i.e., time without toxicities or symptoms of progression [TWiST]) when comparing regimens. Methods: OS in BRIGHT AML 1003 data, restricted to a follow-up of 20 months, was partitioned into time with toxicity (TOX: grade 3+ adverse events prior to progression), TWiST, and time post-progression (REL). Progression was defined as treatment discontinuation due to insufficient clinical response or death; patients who discontinued for other reasons (including adverse events) were censored at the date of discontinuation unless death occurred within 28 days of discontinuation. Q-TWiST was calculated by multiplying restricted mean time in each state by respective utilities (U) and then summing up the utility-adjusted time. Base case analysis used U(TOX)=U(REL)=0.5 and U(TWiST)=1.0; threshold analyses were performed varying U(TOX) and U(REL) jointly each from 0 to 1. Relative gains in Q-TWiST (i.e., Q-TWiST difference (combination vs LDAC) / OS in LDAC arm) of ≥15% were considered clearly clinically meaningful per the clinical literature. Sensitivity analysis varied the length of follow-up and AE definitions; subgroup analyses were also performed. 95% confidence intervals were obtained using the bootstrap procedure. Results: At 20 months of follow-up, the survival rate for glasdegib+LDAC and LDAC arm was 28.2% and 7.9%, respectively. Glasdegib+LDAC patients (n=78) compared with LDAC patients (n=38) had significantly longer mean time in TWiST (+3.4 [95% confidence interval: 1.8, 5.2] months) and TOX (+0.8 [0.1, 1.6] months), and longer but non-significant REL (+0.3 [-1.9, 2.3] months). Q-TWiST was 4.0 [2.1, 5.8] months longer for glasdegib+LDAC, translating into a 75% relative improvement in quality-adjusted survival relative to LDAC alone. In threshold analyses, absolute and relative Q-TWiST gains ranged from 3.5 to 4.5 months and 66% to 85%, respectively (Table 1). They exceeded the clinically meaningful threshold for gains in Q-TWiST and were statistically significant across all combinations of U(TOX) and U(REL). Results were robust to length of follow-up 6 to 24 month and remained significant when including all adverse events regardless of grade. Discussions/Conclusions: Glasdegib+LDAC is an add-on therapy that has demonstrated significant survival benefits for newly diagnosed AML patients who are unable to receive intensive chemotherapy. While patients can experience a longer time with toxicities from receiving glasdegib+LDAC (as expected since it is given as an add-on therapy), the trade-off can still be favorable as the treatment provides added time spent in 'good' health (i.e., a significantly longer time in TWiST). In the BRIGHT AML 1003 cohort, the relative gains in OS greatly exceeded previously established thresholds for being clearly clinically meaningful, which suggests that the benefits of glasdegib+LDAC vs LDAC alone outweigh the risks. Table 1 Disclosures Kwon: Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bell:Pfizer Inc.: Employment, Equity Ownership. Solem:Pharmerit International: Employment; Pfizer Inc.: Research Funding. Cappelleri:Pfizer: Employment, Equity Ownership. Johnson:Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bhattacharyya:Pfizer Inc: Employment, Equity Ownership. Hoang:Pfizer Inc.: Employment, Equity Ownership. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; BiolineRx: Consultancy; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

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Long-Term Cardiac, Vascular, and Hypertension Safety of Bosutinib (BOS) Versus Imatinib (IMA) for Newly Diagnosed Chronic Myeloid Leukemia (CML): Results from the Bfore Trial

Blood ◽

10.1182/blood-2020-134912 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Jorge E. Cortes ◽

Philipp D le Coutre ◽

Carlo Gambacorti-Passerini ◽

Henrik Hjorth-Hansen ◽

Pia Raanani ◽

...

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Research Funding ◽

Study Drug ◽

Newly Diagnosed ◽

Cardiac Events ◽

Publicly Traded ◽

Vascular Events ◽

Serious Adverse Events ◽

History Of

Introduction: Tyrosine kinase inhibitor therapy has been associated with cardiovascular (CV) events. BOS is approved for patients (pts) with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) CML and Ph+ CML resistant/intolerant to prior therapy. We analyzed cardiac, vascular and hypertension treatment-emergent adverse events (TEAEs) in pts with newly diagnosed CP CML receiving BOS or IMA after 5 yrs follow-up in BFORE. Methods: In the open-label, phase 3 BFORE trial (NCT02130557), 536 pts with newly diagnosed CP CML were randomized 1:1 to receive first-line 400 mg once-daily BOS (n=268) or IMA (n=268; 3 untreated). The current analysis included all pts who received ≥1 dose of study drug. TEAEs were monitored from first dose of study drug until 28 d after last dose; monitoring of non-serious adverse events (AE) ended at the start of a new cancer treatment. Prespecified MedDRA terms (cardiac, n=133; vascular, n=502) comprised clusters of investigator-assessed TEAEs (Table). Multivariable proportional subdistribution hazard models predicting time to first TEAE included treatment group; baseline demographic information; history of cardiac events, vascular events, hypertension, diabetes, hyperlipidemia, and tobacco use; as well as hypertension, cardiac (for vascular model) and vascular (for cardiac model) TEAEs. CI excluding 1 was considered predictive of outcome. This analysis was based on 17-Apr-20 last pt last visit (12-Jun-20 database lock), 5 y (240 wks) after last enrolled pt. Results: At study completion, 59.7% of BOS pts and 58.1% of IMA pts were still on treatment. Median duration of treatment was 55 mo for pts receiving BOS or IMA; respective median (range) dose intensity was 393.6 (39-583) vs 400.0 (189-765) mg/d. In the BOS vs IMA arm, 57.8% vs 56.2% of pts had ≥1 CV risk factor at baseline; 20.9% vs 17.7% had ≥3 risk factors, respectively. The most common risk factors were a history of hypertension (BOS, 34.0%; IMA, 30.6%), BMI >30 (BOS, 23.1%; IMA, 21.9%), age ≥65 y (BOS, 19.8%; IMA, 17.4%), and history of hyperlipidemia (BOS, 16.8%; IMA, 18.9%). Rates of cardiac, vascular and hypertension TEAEs; serious adverse events (AEs); AEs leading to treatment withdrawal and drug-related TEAEs (per investigator) were low in both arms (Table). Exposure-adjusted rates of cardiac, vascular and hypertension TEAEs were similar between arms (Table). Risk factors for cardiac TEAEs (HR; 95% CI) were age in years (1.04 [1.02-1.07]), race other than Asian or black compared to white (<0.01 [<0.01-<0.01]), a history of tobacco use (6.94 [1.89-25.40]) and cardiac events (3.59 [1.68-7.65]), hypertension (3.07 [1.20-7.84]) and vascular TEAEs (5.27 [1.53-18.18]). Risk factors for vascular TEAEs (HR [95% CI]) were black race compared to white (<0.01 [<0.01-<0.01]), a history of vascular events (4.65 [1.81-11.97]) and cardiac TEAEs (7.73 [2.31-25.84]). In multivariable analyses, treatment group was not predictive of time to initial cardiac (HR 0.87 [95% CI 0.45-1.70]) or vascular (HR 2.17 [95% CI 0.94-45.04) TEAEs. The most common cardiac, vascular, and hypertension TEAEs, respectively, were sinus bradycardia (2.2%), angina pectoris (3.0%) and hypertension (9.7%) with BOS vs electrocardiogram QT prolongation (3.8%), peripheral coldness (1.1%) and hypertension (10.9%) with IMA. One grade 5 cardiac (acute cardiac failure) and one vascular (myocardial ischemia) TEAE were reported with BOS, and one vascular (cerebrovascular accident) TEAE with IMA; none were considered related to study drug. Successful treatment rechallenge was achieved in the majority of pts with dose interruptions due to cardiac (BOS, 85.7%; IMA, 100%) and vascular (BOS, 100%; IMA, not applicable) TEAEs who were readministered study drug. No pts had dose interruptions due to hypertension TEAEs. Cardiac, vascular and hypertension TEAEs resolved in 57.7%, 75.0% and 35.7% of pts receiving BOS and 65.2%, 66.7% and 48.3% receiving IMA. Conclusions: In this final analysis of BFORE, the incidence of cardiac, vascular, and hypertension TEAEs in pts with newly diagnosed CP CML receiving BOS or IMA was low and was similar between treatment groups. These AEs infrequently led to treatment discontinuation. In addition to continued improved efficacy with BOS vs IMA after 5 yrs follow-up (Brümmendorf et al., ASH 2020), these safety results support the use of first-line BOS as a standard of care in pts with CP CML. Disclosures Cortes: Bristol-Myers Squibb: Research Funding; BiolineRx: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Research Funding; Amphivena Therapeutics: Research Funding; Arog: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Telios: Research Funding; Astellas: Research Funding; Sun Pharma: Research Funding; Merus: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Immunogen: Research Funding. le Coutre:Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Gambacorti-Passerini:Bristol-Myers Squibb: Consultancy; Pfizer: Honoraria, Research Funding. Hjorth-Hansen:Pfizer: Honoraria, Research Funding; Austrian Orphan Pharma: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding. Garcia-Gutiérrez:Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding. Kota:Ariad: Honoraria; Incyte: Honoraria; Xcenda: Honoraria; Novartis: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical, Company Ltd, Cambridge, MA, USA: Honoraria; Pfizer: Consultancy, Honoraria. Purcell:Pfizer: Current Employment, Current equity holder in publicly-traded company. Viqueira:Pfizer: Current Employment, Current equity holder in publicly-traded company. Leip:Pfizer: Current Employment, Current equity holder in publicly-traded company. Brümmendorf:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy; Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Novartis: Consultancy, Other: travel, accommodation, expenses, Research Funding.

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