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In: Cancer, Wiley, Vol. 127, No. 7 ( 2021-04), p. 1039-1048

Abstract: Blinatumomab and inotuzumab ozogamicin have comparable efficacy as a first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia. The sequencing of these novel agents should be tailored according to individual patient needs.

Type of Medium: Online Resource

ISSN: 0008-543X , 1097-0142

URL: Issue

URL: Article

DOI: 10.1002/cncr.v127.7

DOI: 10.1002/cncr.33340

Language: English

Publisher: Wiley

Publication Date: 2021

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detail.hit.zdb_id: 2599218-1

detail.hit.zdb_id: 2594979-2

detail.hit.zdb_id: 1429-1

In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 2, No. suppl_1 ( 2015-12-09)

Type of Medium: Online Resource

ISSN: 2328-8957

URL: Article

DOI: 10.1093/ofid/ofv133.525

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2015

detail.hit.zdb_id: 2757767-3

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4806-4806

Abstract: Background: Patients (pts) with hematologic malignancies have an increased risk of venous thromboembolism (VTE) events, driven by both the underlying cancer and cancer treatment. This risk exists even in acute leukemia (AL) in the setting of profound thrombocytopenia and coagulopathies, which can delay VTE diagnosis and complicate management. We evaluated the incidence of VTE in AL pts during an admission for chemotherapy and determined its effect on the duration of hospital stay and likelihood of intensive care unit (ICU) admission. Methods: All pts admitted to the Cleveland Clinic inpatient leukemia service with a diagnosis of acute myeloid (AML), lymphoblastic (ALL), or promyelocytic leukemia (APL) between January 1, 2013 and March 31, 2018 and treated with high-intensity chemotherapy were included. High intensity regimens for AML and APL included infusional cytarabine and an anthracycline with the addition of ATRA for latter and for ALL included Hyper-CVAD and CALBG regimens. Pts were excluded if they were admitted directly to the ICU or were transferred after initiating chemotherapy from another institution. Cases with VTE were defined using specific ICD-9-CM codes [451.1x, 451.2; 451.81, 453.1, 453.2, 453.8, 453.9, 415.1x; and, in addition, 997.2 or 997.3 when coupled with a secondary diagnosis of VTE]. All VTE cases identified through this strategy via an electronic medical record query were additionally validated on subsequent chart review. Pts with a diagnosis of VTE were matched 1:3 based on age, sex, race, and leukemia subtype to pts who did not experience VTE during the incident admission. Pts were also assessed for administration of prothrombotic agents, including: PEG-asparaginase, oral contraceptives, and tyrosine kinase inhibitors. The length of stay for the incident hospitalization and incidence of ICU admission were compared between pts who did and who did not experience VTE. Results: Of the 400 AL pts admitted to the inpatient leukemia service during the study period to receive high-intensity chemotherapy, 10 (2.5%) had a documented VTE during the admission. Baseline characteristics of the 1:3 matched cohorts (AL with and without VTE) are shown in Table 3. The median age of the AL pts who developed VTE was 54.5 years (range, 20-78 yrs), 60% were females, median platelet count at the time of VTE diagnosis was 117,900/mL [(range, 29-476,000/mL); 4 pts had platelet (plt) counts below 50,000/mL, 8 pts had plt below 100,000/mL; 2 pts had normal plt counts], and four pts had bloodstream infections within 7 days of VTE occurrence. By disease breakdown, four had AML, 3 had APL and 3 had ALL. By treatment course, 9 pts were receiving initial chemotherapy 1 pt was receiving salvage therapy. By VTE site, 8 patients had line associated VTE and 2 patients had pulmonary embolism. Five VTE pts were treated with either unfractionated or low molecular weight heparin, 2 underwent IVC filter placement and 3 were untreated. Pts in the VTE group experienced a longer duration of hospitalization compared to those who did not have a VTE event (29.81 vs 23.13 days, respectively, P=.027), and were more likely to be admitted to the ICU compared to those who did not experience VTE (66.7% vs 14.8%, respectively, P=.010). VTE risk was not associated with use of prothrombotic agents (p=.430). Summary and Conclusion: While the incidence of VTE in our patient population was lower than what has been previously reported, it was associated with a prolonged hospitalization and increased risk of ICU admission. The incidence of VTE was not associated with use of thrombotic agents and VTE events occurred in patients with normal plt counts and even in the setting of moderate or severe thrombocytopenia. While it is unclear if early intervention after the diagnosis of VTE affects clinical outcome, the association with increased length of stay and ICU admission can increase healthcare-associated costs in the current environment with increasing focus on value. Further studies are warranted to characterize the risk factors for VTE in AL population. Disclosures Carraway: Novartis: Speakers Bureau; FibroGen: Consultancy; Jazz: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Advani:Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy; Pfizer: Honoraria, Research Funding. Nazha:MEI: Consultancy. Gerds:Incyte: Consultancy; CTI Biopharma: Consultancy; Apexx Oncology: Consultancy; Celgene: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-115257

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3433-3433

Abstract: Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128807

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Mycoses, Wiley, Vol. 60, No. 4 ( 2017-04), p. 241-243

Abstract: It is unclear if the prophylaxis dose of 300 mg/day is sufficient for achieving serum concentrations targeting the treatment of invasive fungal infections. To evaluate differences between PCZ serum concentrations in patients receiving the DRT vs the OS and in patients receiving higher doses than 300 mg/day of the DRT , a retrospective review was conducted on inpatients who received PCZ for either treatment or prophylaxis. Baseline demographics including comorbid conditions, indication and dose of therapy were collected. Serum trough concentrations were collected at steady state. Fifty‐seven patients received PCZ during the study period. A total of 35 levels were collected ( DRT n = 18, OS n = 17). Patients receiving the DRT had levels 〉 0.7 mcg/mL 100% of the time compared to 58.8% in those receiving the OS . No significant difference was seen in serum concentrations at 300 mg/day (n = 14) vs 400 mg/day (n = 8) of the DRT (1.55 mcg/mL (1.08‐2.50) vs 2.5 mcg/mL (1.85‐2.70), P  = .19). The DRT leads to more consistent levels in the therapeutic range than the OS . Standard dosing of 300 mg/day with DRT achieves adequate concentrations for prophylaxis and treatment of IFI s, although further data are needed to determine optimal serum concentrations for treatment.

Type of Medium: Online Resource

ISSN: 0933-7407 , 1439-0507

URL: Issue

URL: Article

DOI: 10.1111/myc.2017.60.issue-4

DOI: 10.1111/myc.12587

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2020780-3

In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 56, No. 8 ( 2021-08), p. 1998-2004

Type of Medium: Online Resource

ISSN: 0268-3369 , 1476-5365

URL: Article

DOI: 10.1038/s41409-021-01279-w

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2004030-1

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 16-16

Abstract: Background: Clinical trial recruitment is hindered by patient (pt), provider, and organizational barriers. The prohibitory impact of specific comorbidity/organ function criteria, however, has not been studied in the AML pt population. While intended to protect pts, trial eligibility criteria, when excessive, exclude pts irrespective of expected toxicities (Statler et al. Leukemia 2017). Yet, research demonstrates adverse events and outcomes are similar among eligible and ineligible AML pts (Statler et al. Blood 2018). We characterized the multi-morbidity prolife of AML pts prior to induction chemotherapy and compared outcomes among those with and without baseline comorbidities/organ dysfunction that have been used in clinical trial eligibility criteria. Methods: Adult (≥18 years) AML pts who received chemotherapy at Cleveland Clinic from 2003 to 2019 were included. The following characteristics were analyzed: age, sex, self-reported race, insurance, etiology of AML, comorbidities, hepatic/renal function tests, left ventricular ejection fraction (LVEF), and corrected QT interval (QTc). AML risk was categorized according to the 2017 European LeukemiaNet (ELN) risk stratification. Univariate associations between dose modifications and pt characteristics were tested using logistic regression. Cox proportional hazards and logistic regression were used to identify significant prognostic factors for overall survival (OS) and complete remission (CR) status per International Working Group criteria. Kaplan-Meier method was used to estimate median OS. Results: Of 1,082 AML pts analyzed, the median age was 60.6 years (IQR: 50.2, 69.1), 53.1% (n=574) were male, 86.8% (n=939) were white, and 45.7% (n=494) had Medicare insurance. A majority (n=680, [62.9%]) had de novo AML, and 55.3% (n=598) had intermediate-risk disease. Pts were treated with: intensive cytarabine-based (n=901 [83.3%] ), or non-intensive (low-dose cytarabine or hypomethylating agents (n=181 [16.7%]). Of those with comorbidities, the most common were vascular (n=540 [49.9%] ), endocrine (n=272 [25.1%]), and neurological (n=220, [20.3%] ) (Tables 1 and 2). With a median follow-up of 12.9 (IQR: 4.67-43.13) months, the median OS for the cohort was 15.1 months (range 0.03-189.25). In multivariate analyses controlling for treatment, age, sex, insurance, number of comorbidities, AML etiology, and ELN risk, the only comorbidity associated with OS was liver disease (HR=1.90, P=.004). However, baseline AST (3xULN vs. normal: HR=1.02, P=.94; & gt;3-5x ULN vs. normal: HR=1.42, P=.30.), ALT (3xULN vs. normal: HR=0.76, p=0.45, & gt;3-5xULN vs. normal: HR=1.58, P=.23) and bilirubin (1.5xULN vs. normal: HR=1.34, P=.08) were not associated with a worse OS. Minor renal dysfunction was also not associated with OS, when measured by creatinine (1.5xULN vs. normal: HR=1.06, P=.52) or creatinine clearance by Cockcroft-Gault (CrCl 84-60 ml/min: HR=0.95, P=.62). Baseline LVEF abnormalities, though, were associated with increased mortality, and as severity increased the effect size increased in a dose-response fashion (50-40%: HR=1.38, P=.04; & lt;40%: HR=1.66, P=.009). The pattern for baseline prolonged QTc was similar; increasing values of QTc was associated with increased mortality ( & gt;480ms: HR=1.36, P=.04; ≥501: HR=1.72, 95%, P=.001). With the exception of liver comorbidities (OR=0.26, P=.03), our analysis failed to identify significant evidence of association between response and comorbidities/organ dysfunction. Comorbidities and liver function abnormalities were also not associated with dose modifications during AML treatment, while pts with clinically significant renal (CrCl ≤ 30 ml/min) and/or cardiac (LVEF ≤50%) abnormalities at baseline did have a higher odds of a dose reduction in univariate analysis. Conclusions: The majority of AML pts within this cohort (n=953 [88.1%]) presented with at least 1 comorbidity and/or 1 clinically insignificant liver or renal abnormality that could have excluded them from clinical trials. Yet, survival, response, and dose modification outcomes did not significantly differ between pts with and without comorbid conditions or minor liver/renal abnormalities. These results suggest future AML trials may liberalize comorbidity and organ function eligibility criteria, which will likely improve recruitment rates and provide equitable access to investigational products. Disclosures Hobbs: SimulStat Inc.: Consultancy; Amgen: Research Funding. Mukherjee:Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor. Advani:Abbvie: Research Funding; Macrogenics: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Kite Pharmaceuticals: Consultancy; Glycomimetics: Consultancy, Research Funding. Gerds:Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Roche: Research Funding; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy; Celgene Corporation: Consultancy, Research Funding. Nazha:Tolero, Karyopharma: Honoraria; MEI: Other: Data monitoring Committee; Novartis: Speakers Bureau; Jazz Pharmacutical: Research Funding; Incyte: Speakers Bureau; Daiichi Sankyo: Consultancy; Abbvie: Consultancy. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-130319

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1838-1838

Abstract: Introduction: Daratumumab (DARA) is an anti-CD38 human monoclonal antibody FDA-approved for the treatment of multiple myeloma (MM) and has demonstrated efficacy in AL amyloidosis. Infusion-related reactions (IRRs) occur in over 50% of patients treated with DARA, most commonly with the first infusion despite premedication with corticosteroids, antipyretics, antihistamines, and post-infusion corticosteroids. If DARA is tolerated without IRRs, the infusion rate can be escalated in standardized increments to a final infusion rate administered over 90 minutes in patients with MM (Barr et al. Leukemia 2018). Rapid infusions of DARA decrease length of infusion visits, potentially improving patient satisfaction and optimizing healthcare resources. Recent studies showed that DARA is safe and highly effective in treating AL amyloidosis (Khouri et al, Br J Haematol 2018), but no information is available regarding the safety of administering rapid infusions of DARA in patients with AL amyloidosis. We hypothesized that patients with AL amyloidosis, especially those with cardiac involvement, may not tolerate a rapid administration of fluids. Thus, a DARA rapid infusion protocol for patients with AL amyloidosis was implemented at our institution in April 2018. We report findings from the protocol implementation. Methods: A retrospective observational study was conducted to review adult patients with AL amyloidosis who received rapid infusions of DARA from April 2018 to October 2018. Data collected included relevant past medical history, vitals, premedications, infusion rates, and management of IRRs. Patients were eligible for rapid DARA after tolerating two prior doses of DARA at standard infusion rates. Rapid DARA was infused at 200 mL/hr for 30 minutes, then increased to 450 mL/hr for 60 minutes. Protocol premedications included acetaminophen, diphenhydramine, famotidine, and dexamethasone. No post-infusion corticosteroids were required. The first two standard and first four rapid DARA infusions were evaluated for each patient. Results: 27 patients with AL amyloidosis were included in the study with 162 doses of rapid DARA evaluated. Baseline characteristics included age (median 72 years old), gender (55.6% male), diastolic heart failure (59.3%), combined systolic and diastolic heart failures (11.1%), chronic obstructive pulmonary disease (7.4%), asthma (7.4%), and chronic kidney disease (25.9%). 62.9% of patients had cardiac AL involvement and 51.9% had renal AL involvement. 11/27 (40.7%) patients had IRRs to the first infusion of DARA (cycle 1, day 1) requiring hypersensitivity medications. All 27 patients progressed to rapid rate DARA after both initial and subsequent rates were tolerated. 22/27 (81.5%) patients initiated the first rapid DARA with the protocol premedications. Premedication usage decreased by the fourth rapid DARA dose with only 23.1% patients receiving diphenhydramine, 57.7% receiving famotidine, and 38.5% receiving dexamethasone (Figure 1). No patients received post-infusion corticosteroids. There were no clinically significant IRRs with the DARA rapid infusion protocol across all patients, regardless of organ involvement. There were 10 cases of CTCAE grade 2-3 hypertension that did not require intervention. No hypersensitivity medications were required for any rapid DARA doses. 11/11 (100%) patients who experienced IRRs requiring hypersensitivity medications during their first or second standard DARA infusions tolerated rapid DARA administration without recurrence of IRRs. Conclusions: Rapid administration of DARA is safe and well-tolerated in patients with AL amyloidosis, regardless of organ involvement. Patients who experienced an IRR with the initial DARA dose were able to safely transition to the rapid infusion protocol without recurrence of IRRs. Furthermore, decreased premedication usage after tolerance of rapid DARA infusion did not increase IRRs, suggesting premedications can be discontinued to mitigate associated toxicities. Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau. Valent:Celgene corporation: Speakers Bureau; Amgen corporation: Speakers Bureau; Takeda pharmaceuticals: Speakers Bureau. OffLabel Disclosure: Daratumumab for the treatment of AL amyloidosis

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-124775

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 1-1

Abstract: Treatment options are limited for patients (pts) diagnosed with MDS at the time of hypomethylating agent (HMA) failure. One goal is to introduce another line of therapy to reduce tumor burden and enable patients to undergo hematopoietic stem cell transplant (HSCT), which may prolong survival for a subset. CPX-351, has shown better overall response rates and improved overall survival in patients with acute myeloid leukemia with underlying MDS changes compared to 7+3, suggesting that CPX-351 can be used in an MDS patient population. We hypothesized that treating MDS pts, who were failed by HMAs or were intolerant with CPX-351 would overcome HMA resistance. This is a phase II study of single agent CPX-351 administered at the standard FDA approved dose of 44 mg/m2 (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) intravenously on days 1, 3, 5 of the induction cycle. If patients achieve complete remission (CR), marrow CR, partial remission or hematologic improvement per 2006 IWG criteria they will be eligible to continue on to consolidation therapy, which consists of CPX-351 at a dose of 15.4 mg/m2 (daunorubicin 15.4 mg/m2 and cytarabine 35 mg/m2) every 28 days. Pts can receive up to 4 cycles of consolidation therapy in the absence of toxicity. The primary objective of the trial is to evaluate the efficacy of CPX-351 as measured by overall response rate (ORR) by IWG 2006 criteria. Secondary objectives include: ,1) determine the time to response (TTR), 2) evaluate the duration of response (DOR), 3) evaluate the event-free survival and the overall survival probability during trial period. Pts are risk stratified into lower vs higher-risk prior to enrollment using the Post-HMA model (Nazha A, et al. Hematologica 2016). Eligibility includes: pts & gt;18 years with primary or secondary resistance to HMA, ECOG performance status & lt; 2 and adequate organ function. Pts are excluded if they have uncontrolled infection or active malignancy. A total of 18 pts will be enrolled to each arm (lower and higher risk). To date, three pts were enrolled. One with MDS refractory to HMA who achieved complete remission and proceeded with 4 cycles of consolidation. The pt remained in remission 6+ months after the completion of consolidation. Another patient achieved a marrow CR but had a fungal pneumonia and then was taken off the trial (patient choice for going to hospice). The third patient had MDS/MPN, completed induction and achieved stable disease with improvement in platelets and neutrophils. All patients were lower-risk per the stratification model. No unexpected toxicity was observed. In conclusion, preliminarily CPX-351 is effective in MDS patients after HMA failure who are eligible to receive intensive chemotherapy. The treatment was well tolerated and toxicities were similar to what was observed in pivotal CPX-351 trials. The trial is ongoing and the results will be updated in the meeting. Disclosures Nazha: MEI: Other: Data monitoring Committee; Novartis: Speakers Bureau; Incyte: Speakers Bureau; Jazz: Research Funding. Mukherjee:Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EUSA Pharma: Consultancy; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Bristol Myers Squib: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Aplastic Anemia and MDS International Foundation: Honoraria. Advani:Abbvie: Research Funding; Macrogenics: Research Funding; Glycomimetics: Consultancy, Other: Steering committee/ honoraria, Research Funding; Immunogen: Research Funding; Seattle Genetics: Other: Advisory board/ honoraria, Research Funding; Amgen: Consultancy, Other: steering committee/ honoraria, Research Funding; Kite: Other: Advisory board/ honoraria; Pfizer: Honoraria, Research Funding; Novartis: Consultancy, Other: advisory board; OBI: Research Funding; Takeda: Research Funding. Carraway:Jazz: Consultancy, Speakers Bureau; BMS: Consultancy, Other: Research support, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Takeda: Other: Independent Advisory Committe (IRC); Novartis: Consultancy, Speakers Bureau; Abbvie: Other: Independent Advisory Committe (IRC); ASTEX: Other: Independent Advisory Committe (IRC). Gerds:AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding; Roche/Genentech: Research Funding; CTI Biopharma: Consultancy, Research Funding; Imago Biosciences: Research Funding; Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Gilead Sciences: Research Funding; Apexx Oncology: Consultancy; Pfizer: Research Funding. Patel:Alexion: Other: educational speaker. Sekeres:Takeda/Millenium: Consultancy; Pfizer: Consultancy; BMS: Consultancy. OffLabel Disclosure: CPX-351 in MDS

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-139515

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood Advances, American Society of Hematology, Vol. 4, No. 10 ( 2020-05-26), p. 2308-2316

Abstract: The availability and use of blinatumomab symbolizes a paradigm shift in the management of B-cell acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter cohort analysis of 239 ALL patients (227 relapsed refractory [RR], n = 227; minimal residual disease [MRD] , n = 12) who received blinatumomab outside of clinical trials to evaluate safety and efficacy in the “real-world” setting. The median age of patients at blinatumomab initiation was 48 years (range, 18-85). Sixty-one (26%) patients had ≥3 prior therapies and 46 (19%) had allogeneic hematopoietic cell transplantation before blinatumomab. The response rate (complete remission/complete remission with incomplete count recovery) in patients with RR disease was 65% (47% MRD−). Among 12 patients who received blinatumomab for MRD, 9 (75%) patients achieved MRD negativity. In patients with RR disease, median relapse-free survival and overall survival (OS) after blinatumomab was 32 months and 12.7 months, respectively. Among patients who received blinatumomab for MRD, median relapse-free survival was not reached (54% MRD− at 2 years) and OS was 34.7 months. Grade ≥3 cytokine release syndrome, neurotoxicity, and hepatotoxicity were observed in 3%, 7%, and 10% of patients, respectively. Among patients who achieved complete remission/complete remission with incomplete count recovery, consolidation therapy with allogeneic hematopoietic cell transplantation retained favorable prognostic significance for OS (hazard ratio, 0.54; 95% confidence interval, 0.30-0.97; P = .04). In this largest “real-world” experience published to date, blinatumomab demonstrated responses comparable to those reported in clinical trials. The optimal sequencing of newer therapies in ALL requires further study.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2019001381

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 2876449-3