scholarly journals Azacitidine (Onureg)

2022 ◽  
Vol 2 (1) ◽  
Author(s):  
Reimbursement Team
Keyword(s):  
Complete Remission ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Drug Class ◽  
Clinical Effectiveness ◽  
Hematopoietic Stem ◽  
Consolidation Treatment ◽  
Clinician Perspectives ◽  
Acute Myeloid ◽  
Count Recovery

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses azacitidine (Onureg), tablet 300 mg, oral. Indication: Maintenance therapy in adult patients with acute myeloid leukemia who achieved complete remission or complete remission with incomplete blood count recovery following induction therapy with or without consolidation treatment, and who are not eligible for hematopoietic stem cell transplantation.

Survival Outcomes In Relapsed/Refractory Acute Myeloid Leukemia Patients Who Achieve Less-Than-Complete Response After Salvage Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2654-2654 ◽  
Author(s):  
Shilpan S. Shah ◽  
Hagop M Kantarjian ◽  
Farhad Ravandi ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Number Of Patients ◽  
Acute Myeloid ◽  
Refractory Aml ◽  
Count Recovery

Abstract Background Patients with acute myeloid leukemia (AML) who achieve complete remission (CR) after frontline therapy have better outcomes in terms of relapse-free survival and overall survival than those who fail to achieve CR. Patients that achieve complete remission with incomplete platelet recovery (CRp) have an inferior outcome than those with CR, but better than those with no response (Walter et al, JCO 2010). In the setting of relapsed or refractory patients who receive salvage therapy, responses such as CRp and CR with incomplete blood count recovery (CRi) may be seen more frequently. However the clinical benefit of such responses is not known. Aim To evaluate if less-than-complete remissions (CRi) after salvage therapy impact overall survival in relapsed or refractory AML patients when compared to complete remission and no response. Methods We conducted a retrospective analysis of all patients who received salvage therapy (1st and 2nd salvage only) for relapsed or refractory AML at our institution between 2010 and 2012. To assess achievement of response, patients usually have to survive at least 4 weeks as the bone marrow assessment is done at this time. Thus, to adjust for the lead-time bias of patients who achieved any kind of response, only patients who survived at least 4 weeks from the initiation of therapy were included in the analysis. The responses were classified into 3 categories – 1. Complete remission (CR); 2. Incomplete response which includes incomplete blood count recovery (CRi), morphologically leukemia free (MLF), partial response (PR) and 3. No response. Response categories were defined according to the International Working Group response definitions (Cheson et al, 2003). Results During the observation period, 217 patients received 1st or 2nd salvage therapy. Twenty-one of these patients died before 4 weeks after initiation of treatment and were therefore excluded from this analysis. Median age of all patients was 60 years (18-86). 118 patients had received one prior therapy (i.e., 1st salvage group) while 78 had two prior therapies (i.e., 2nd salvage group). Salvage therapy for this analysis was heterogeneous and was classified into hypomethylating agent based therapy in 23 (12%) patients, high-dose cytarabine (>500mg/m2) based regimens in 133 (68%) patients and various investigational regimens in 40 (20%) patients. The last group included investigational new agents or standard agents (other than hypomethylating or cytarabine) being studied in investigational doses or combinations. Prognostic groups based on cytogenetics showed 11(6%), 25(13%), 71(36%) and 76(38%) patients had favorable, intermediate, diploid and adverse cytogenetics, respectively. In 13 (7%) patients, we had insufficient or no sample for cytogenetics. Thirty-five (18%) were FLT3-ITD positive, FLT D835 point mutation was positive in 10 (5%) patients, 2 patients had both ITD and point mutation and FLT3 status was not available in 8(4%) patients; all others were negative. After salvage therapy, 39 (20%) patients achieved CR at some point in their therapy. CRi/PR/MLF was seen in 35 (18%) patients and remaining had no response. Within the CRi/PR/MLF group, the number of patients achieving CRi, MLF and PR were 28, 6 and 1, respectively. The median survival of all patients was 28.4 weeks. Median overall survival for patients in three groups was 79 weeks, 45 weeks and 27 weeks, respectively (p<0.001). Considering only patients receiving 1st salvage therapy, the median survivals for the three groups were 45.6, 41.0 and 28.9 weeks, respectively. Corresponding values for those receiving 2nd salvage were 42.1, 28.1 and 26.7 weeks, respectively. A total of 62(31%) patients received stem cell transplant out of which 47 (24%) had received it after the salvage therapy. Three patients had received two stem cell transplants and salvage therapy was in between the two. The number of patients receiving transplant in three groups (CR, CRi and no response) were 21 (11%), 16(8%) and 13(7%), respectively. Conclusions This analysis suggests that achievement of CRi, MLF or PR in AML patients receiving 1st or 2nd salvage therapy is associated with clinical benefit manifested by improved survival. Although CR still confers the greatest benefit, lesser responses also have a significant impact in survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Platelet Factor-4 Is an Indicator of Blood Count Recovery in Acute Myeloid Leukemia Patients in Complete Remission

2007 ◽  
Vol 7 (2) ◽  
pp. 431-441 ◽  
Author(s):  
Jin Young Kim ◽  
Ho-Jun Song ◽  
Hoi-Jeong Lim ◽  
Myung-Geun Shin ◽  
Jae Seong Kim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Acute Myeloid ◽  
Count Recovery

scholarly journals Daunorubicin and Cytarabine Liposome (Vyxeos)

2021 ◽  
Vol 1 (10) ◽  
Author(s):  
Reimbursement Team
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cost Effectiveness ◽  
Myeloid Leukemia ◽  
Drug Class ◽  
Clinical Effectiveness ◽  
Newly Diagnosed ◽  
Clinician Perspectives ◽  
Acute Myeloid

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses dunorubicin and cytarabine liposome for injection, 44 mg daunorubicin and 100 mg cytarabine per vial, IV infusion Indication: Treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes

Impact of Incomplete Blood Count Recovery Prior to Allogeneic Hematopoietic Stem Cell Transplantation on Engraftment and Early Infection in Patients with Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3408-3408 ◽  
Author(s):  
Takeru Asano ◽  
Shuntaro Ikegawa ◽  
Tomoko Inomata ◽  
Naoto Ikeda ◽  
Hiroyuki Sugiura ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Low Dose ◽  
Early Infection ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid ◽  
Neutrophil Engraftment ◽  
Count Recovery

Abstract Introduction: Hematological complete remission (CR) is the evident prognostic factor of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with Acute Myeloid Leukemia (AML). CR with incomplete blood cell count recovery (CRi) after induction therapy was identified as independent prognostic factor for inferior long-term outcomes in patients with AML achieving remission (Chen et al, JCO 2015). There is a paucity of data regarding the impact of response (CR vs. CRi) prior to allogeneic HSCT. Here we examined whether CRi provide prognostic information on the transplant outcomes. Methods: We retrospectively analyzed 73 consecutive adults with AML who received first allogeneic HSCT between 2008 and 2015. All clinical data were collected from medical records. CRi were defined CR with absolute neutrophil count < 1,000/mm3 and/or platelet count < 100,000/mm3. CR and CRi were confirmed just prior to allogeneic HSCT in bone marrow and peripheral blood. Cytogenetic risk group was assigned based on CIBMTR criteria. Chemotherapy regimens prior to allogeneic HSCT defined as follows; standard-dose (cytarabine plus anthracycline), high-dose (cytarabine at individual dose ≥ 1g/m2 with or without other drugs), low-dose (azacitidine or low dose cytarabine). Categorical and continuous variables were analyzed using Fisher's exact test and Mann-Whitney U test, respectively. Overall survival (OS) and relapse free survival (RFS) were estimated by Kaplan-Meiyer method. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM), engraftment rate and cumulative infectious events were calculated using Grayfs method. Multivariate analysis was performed using the Fine-gray proportional hazard regression model for NRM and cumulative infectious events. Results: A total of 48 (66%) were in CR and 25 (34%) in CRi. The characteristics of the study population, donors and transplants stratified by blood count recovery pre-HSCT are summarized in Table 1. There were several statistically differences between patients in CR and CRi. More patients in CR had longer time from final chemotherapy to HSCT, lower HCT-CI and a higher proportion of major ABO mismatch donor. Median follow-up from allogeneic HSCT was 18 months (range, 1 to 80 months) in the patients still alive. Patients in CR and CRi had a similar 2-year OS (63% vs. 60%, p = 0.29), 2-year RFS (58% vs. 54%, p = 0.42) and 2-year CIR (30% vs. 19%, p = 0.64). 2-year NRM was significantly higher for patients in CRi (17% vs. 34%, p = 0.046) (Figure 1). Ten patients in CRi (40%) died after allogeneic HSCT. One patient died from relapse of AML. Causes of NRM were infection (n=2), veno-occlusive disease (n=3), respiratory failure (n=3) and chronic graft-versus-host disease (n=1). The median time of neutrophil engraftment was 15 days for patients in CR (range, 10 to 25 days) and 18 days for patients in CRi (range, 11 to 49 days). Engraftment rate of neutrophil for patients in CR and CRi was 96% and 92%, respectively. 2 patients in CRi died before neutrophil engraftment. Engraftment rate of neutrophil within 30 days after allogeneic HSCT was significantly lower for patients in CRi (96% vs 84%, p = 0.037). The median time of platelet engraftment was 22 days for patients in CR (range, 10 to 77 days) and 26 days for patients in CRi (range, 12 to 164 days). Engraftment rate of platelet for patients in CR and CRi was 92% and 80%, respectively. 3 patients in CRi died before platelet engraftment. Engraftment rate of platelet within 60 days after allogeneic HSCT was lower for patients in CRi (85% vs. 65%, p = 0.093). To assess the effect of delayed engraftment, we examined infectious events, including bacteria, fungus and virus, within 60 days after allogeneic HSCT. Significantly more patients in CRi had higher cumulative infectious events (46% vs. 72%, p = 0.0086) (Figure 2). There was no bleeding event within 60 days after allogeneic HSCT. Multivariate analysis demonstrated that CRi was an independent risk factor of early infection after allogeneic HSCT (hazard ratio: HR 2.65, 95% CI: 1.37-5.08, p = 0.0037) without a difference in NRM (HR 1.21, 95% CI: 0.26-5.59, p = 0.81). Conclusion: Our data, although retrospectively collected, show that incomplete blood count prior to allogeneic HSCT is a predictable marker of early infection after HSCT in patients with AML. This suggests that we need to develop prophylactic strategies for early infection after allogeneic HSCT based on risk assessments. Disclosures Maeda: Mundipharma KK: Research Funding.

scholarly journals Impact of blood count recovery on outcomes of acute myeloid leukemia patients achieving morphologic leukemia-free state

2018 ◽  
Vol 8 (6) ◽  
Author(s):  
Wen-Yan Cheng ◽  
Yong-Mei Zhu ◽  
Zhao Liu ◽  
Xiang-Qin Weng ◽  
Jing-Ni Sui ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Free State ◽  
Acute Myeloid ◽  
Count Recovery

Necrotizing Hemorrhagic Gastritis following Acute Myeloid Leukemia Induction with Midostaurin: An Unexpected Complication

2019 ◽  
Vol 143 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Shai Shimony ◽  
Hilla Reiss Mintz ◽  
Yulia Shvartser Beryozkin ◽  
Avivit Shoham ◽  
Pia Raanani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blood Count ◽  
Chemotherapy Regimen ◽  
Rare Complication ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Multikinase Inhibitor ◽  
Acute Myeloid ◽  
Count Recovery

Midostaurin is a tyrosine multikinase inhibitor approved for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) with mutated Fms-like tyrosine kinase-3. We describe a case report of a 49-year-old AML patient treated with an intensive chemotherapy regimen followed by midostaurin. After achieving complete remission with blood count recovery, he suffered from a serious, rare complication of necrotizing hemorrhagic gastritis with no evidence of infection or malignant infiltration, possibly associated with midostaurin therapy.

scholarly journals Clinical Outcomes Following Treatment with Gilteritinib or Quizartinib in Patients with Relapsed/Refractory FLT3-ITD+ Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Alexander E. Perl ◽  
Qiaoyang Lu ◽  
Alan Fan ◽  
Nahla Hasabou ◽  
Erhan Berrak ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Phase 3 ◽  
Hematopoietic Stem ◽  
Travel Costs ◽  
Baseline Characteristics ◽  
Acute Myeloid

Background: Gilteritinib is approved for patients (pts) with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML), based on findings from the phase 3 ADMIRAL trial (Perl AE, et al. N Engl J Med. 2019). A phase 3 trial, QuANTUM-R, demonstrated the benefit of quizartinib in pts with R/R AML with FLT3 internal tandem duplication (FLT3-ITD) mutations (Cortes JE, et al. Lancet Oncol. 2019). Although eligibility criteria across both studies were similar, QuANTUM-R was more stringent as to prior therapy intensity and remission duration, which potentially enriched for higher-risk pts. We sought to describe outcomes from ADMIRAL among pts who otherwise met eligibility for QuANTUM-R. Methods: In this post-hoc analysis, a subset of pts from ADMIRAL were matched with R/R FLT3-ITD+ AML pts from QuANTUM-R on the basis of baseline characteristics and prior treatment criteria. Matched pts were either refractory to initial anthracycline-based chemotherapy or had relapsed ≤6 mos after achieving composite complete remission (CRc) with an anthracycline-based regimen. Results: Overall, 218 pts with R/R FLT3-ITD+ AML in the ADMIRAL trial (gilteritinib, n=140; salvage chemotherapy [SC], n=78) were matched with the QuANTUM-R intention-to treat (ITT) population (N=367; quizartinib, n=245; SC, n=122). Proportions of pts preselected for high-intensity SC were 66% (n=143/218) in the matched ADMIRAL ITT population and 77% (n=281/367) in the QuANTUM-R ITT populations. Demographic and baseline characteristics of the matched ADMIRAL ITT population and QuANTUM-R ITT population were similar. Median durations of exposure to gilteritinib and quizartinib were 3.8 mos and 3.2 mos, respectively, and median number of treatment cycles received were five and four, respectively. Rates of hematopoietic stem cell transplantation (HSCT) were similar in pts treated with gilteritinib (35%; n=49/140) or quizartinib (32%; n=78/245), as were the proportions of pts who resumed gilteritinib (23%; n=32/140) or quizartinib (20%; n=48/245) therapy post-HSCT. Median overall survival (OS) in pts treated with gilteritinib or quizartinib was longer than that observed with SC. After a median follow-up of 17.4 mos, median OS was 10.2 mos with gilteritinib versus 5.6 mos with SC (hazard ratio [HR]=0.573 [95% CI: 0.403, 0.814]; one-sided nominal P=0.0008). After a median follow-up of 23.5 mos, median OS with quizartinib was 6.2 mos versus 4.7 mos with SC (HR=0.76 [95% CI: 0.58-0.98]; one-sided P=0.02). After censoring for HSCT, median OS was 9.3 mos with gilteritinib versus 5.5 mos with SC (HR=0.525 [95% CI: 0.356-0.775]; nominal one-sided P=0.0005), and 5.7 mos versus 4.6 mos with quizartinib versus SC, respectively (HR=0.79 [95% CI: 0.59, 1.05]; one-sided P=0.05). In both QuANTUM-R and matched ADMIRAL populations, the survival benefits of quizartinib and gilteritinib compared with SC were maintained across multiple subgroups, including high FLT3-ITD allelic ratio subsets. Compared with SC, high CRc rates were observed in pts treated with either gilteritinib (57%; n=80/140) or quizartinib (48%; n=118/245). The complete remission (CR) rate with gilteritinib was 23% (n=32/140), whereas the CR rate with quizartinib was 4% (n=10/245) (Table). Median time to achieve CRc was 1.8 mos with gilteritinib and 1.1 mos with quizartinib, median duration of CRc was 5.5 mos with gilteritinib and 2.8 mos with quizartinib. The safety profiles of gilteritinib and quizartinib were generally similar, though aspartate or alanine aminotransferase elevations (any grade) were more frequent with gilteritinib (41-44%) than quizartinib (≤13%), whereas neutropenia (14% vs 34%, respectively), fatigue (24% vs 39%, respectively), and prolonged QT intervals (9% vs 27%, respectively) were more frequent with quizartinib. Conclusions: In pts with R/R FLT3-ITD+ AML and similar baseline characteristics, both gilteritinib and quizartinib were generally well tolerated and associated with improved survival and treatment response compared with SC. Responses to gilteritinib and quizartinib, as measured by CRc, were similar; blood count recovery varied between the two FLT3 inhibitors. Although cross-study comparisons have substantial limitations, the findings suggest that while remission is achieved faster with quizartinib, response may be more durable and survival potentially longer with gilteritinib. Disclosures Perl: Syndax: Consultancy, Honoraria; Leukemia & Lymphoma Society, Beat AML: Consultancy; Novartis: Honoraria, Other, Research Funding; Agios: Consultancy, Honoraria, Other; Jazz: Honoraria, Other; FORMA Therapeutics: Consultancy, Honoraria, Other; Daiichi Sankyo: Consultancy, Honoraria, Other: Writing/editorial support, travel costs for meetings, Research Funding; FUJIFILM Pharmaceuticals USA, Inc: Research Funding; New Link Genetics: Honoraria, Other; Arog Pharmaceuticals Inc: Other: uncompensated consulting, travel costs for meetings; Actinium Pharmaceuticals Inc: Consultancy, Honoraria, Research Funding; Biomed Valley Discoveries: Research Funding; Astellas: Consultancy, Honoraria, Other: writing/editorial support, travel costs for meeting presentations related to study, Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; AbbVie Inc: Consultancy, Honoraria, Other, Research Funding; Takeda: Honoraria, Other: Travel costs for meeting; Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Consultancy, Honoraria, Other. Lu:Astellas: Current Employment. Fan:Astellas Pharma: Current Employment. Hasabou:Astellas Pharma: Current Employment. Berrak:Astellas: Current Employment. Tiu:Eli Lilly & Company: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Astellas Pharma Global Development: Current Employment.

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