Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia
Older patients with acute chronic myelocytic leukemia (AML) respond poorly to plain induction medical aid. B-cell malignant neoplastic disease two (BCL-2) overexpression is involved in survival of AML cells and treatment resistance. we have a tendency to report safety and effectiveness of venetoclax with decitabine or azacitidine from an oversized, multicenter, part 1b dose-escalation and growth study. Patients (N = 145) were a minimum of sixty five years recent with treatment-naive AML and were ineligible for intensive therapy. throughout dose step-up, oral venetoclax was administered at four hundred, 800, or 1200 mg daily together with either decitabine (20 mg/m2, days 1-5, intravenously [IV]) or azacitidine (75 mg/m2, days 1-7, IV or subcutaneously). within the growth, four hundred or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was seventy four years, with poor-risk genetics in forty nine of patients. Common adverse events (>30%) enclosed nausea, diarrhea, constipation, febrile leukopenia, fatigue, symptom, attenuated appetency, and attenuated white blood corpuscle count. No growth lysis syndrome was determined. With a median time on study of eight.9 months, sixty seven of patients (all doses) achieved complete remission (CR) + metallic element with incomplete count recovery (CRi), with a metallic element + CRi rate of seventy three within the venetoclax four hundred mg + HMA cohort. Patients with poor-risk genetics and people a minimum of seventy five years recent had metallic element + CRi rates of sixtieth and sixty five, severally. The median period of metallic element + CRi (all patients) was eleven.3 months, and median overall survival (mOS) was seventeen.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in old patients with AML (This trial was registered at computer network.clinicaltrials.gov as #NCT02203773). [1]
Gemtuzumab Ozogamicin For De Novo Acute Myeloid Leukemia: Final Efficacy And Safety Updates From The Open-Label, Phase III ALFA-0701 Trial
The irregular, clinical test ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin additional to plain front-line therapy considerably improves event-free survival (EFS) in adults with de novo acute granulocytic leukemia (AML). Here we tend to report associate degree freelance review of EFS, final overall survival (OS), and extra safety results from ALFA-0701. Patients (n=271) aged 50-70 years with Delaware novo AML were irregular to receive standard front-line induction therapy (3+7daunorubicin+cytarabine) with/without gemtuzumab ozogamicin three mg/m2 on days one, 4, and seven throughout induction. Patients arrested following induction medical aid received a pair of courses of consolidation therapy (daunorubicin+cytarabine) with/without gemtuzumab ozogamicin (3 mg/m2/day on day 1) in keeping with their initial randomisation. the first finish purpose was investigator-assessed EFS. Secondary finish points enclosed OS and safety. A blind freelance review confirmed the investigator-assessed EFS results [August one, 2011; hazard magnitude relation (HR) zero.66; ninety five Confidence Interval (CI): zero.49–0.89; 2-sided P=0.006], adore a thirty four reduction in risk of events within the gemtuzumab ozogamicin versus management arm. Final OS at Gregorian calendar month thirty, 2013 favored gemtuzumab ozogamicin however wasn’t important. No variations in early death rate were discovered between arms. the most toxicity related to gemtuzumab ozogamicin was prolonged blood disease. Veno-occlusive unwellness (including when transplant) was discovered in vi patients within the gemtuzumab ozogamicin arm and a pair of in the management arm. last, gemtuzumab ozogamicin additional to plain intensive therapy features a favorable
benefit/risk magnitude relation. These results expand front-line treatment choices for adult patients with antecedently untreated AML. (Trial registered at clinicaltrials.gov; identifier: 00927498.)
Received Gregorian calendar month seventeen, 2018.
Accepted July twenty five, 2018.
Copyright© 2019 Ferrata Storti Foundation
Material printed in Haematologica is roofed by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of printed material is allowed beneath the subsequent terms and conditions:
https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of printed material are allowed for private or internal use. Sharing printed material for non-commercial functions is subject to the subsequent conditions:
https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing printed material for industrial functions isn’t allowed while not permission in writing from the publisher. [2]
Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome
Glasdegib may be a Hedgehog pathway matter. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the effectiveness of glasdegib and low-dose cytarabine (LDAC) in patients with acute chronic myelocytic leukemia (AML) or unsound myelodysplastic syndrome unsuitable for intensive therapy. Glasdegib 100 mg (oral, QD) was administered incessantly in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for ten per twenty eight days. Patients (stratified by cytogenetical risk) were randomised (2:1) to receive glasdegib/LDAC or LDAC. the first end was overall survival. cardinal and forty four patients were randomised to glasdegib/LDAC and LDAC, severally. Median (80% confidence interval [CI]) overall survival was eight.8 (6.9–9.9) months with glasdegib/LDAC and four.9 (3.5–6.0) months with LDAC (hazard magnitude relation, 0.51; 80% CI, 0.39–0.67, P = 0.0004). Fifteen (17.0%) and one (2.3%) patients within the glasdegib/LDAC and LDAC arms, severally, achieved complete remission (P [3]
Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group
Acute dedifferentiated leukemia could be a rare style of leukemia that shows no proof of differentiation on any lineage. Clinical, immunophenotypic and genetic knowledge is restricted and it’s unsure if acute dedifferentiated leukemia is biologically distinct from acute myelocytic leukemia with nominal differentiation, that conjointly shows restricted myeloid marker expression and has been rumored to possess a poor prognosis. we tend to known ninety two cases ab initio diagnosed as acute dedifferentiated leukemia or acute myelocytic leukemia with nominal differentiation from pathology knowledgebases of 9 tutorial establishments with out there diagnostic flow cytometric data, cytology findings, modification and clinical knowledge. Outcome analysis was performed victimisation Kaplan Meier take a look at for the fifty three patients World Health Organization received
induction therapy. supported cytology abnormalities (N = 30) or history of myelodysplastic syndrome (N = 2), thirty two cases were re-classified as acute myelocytic leukemia with myelodysplasia connected changes. The remaining twenty four acute dedifferentiated leukaemia patients bestowed with similar age, blood counts, bone marrow physiological state, and blast proportion because the remaining thirty acute myelocytic leukemia with nominal differentiation patients. Compared to acute myelocytic leukemia with nominal differentiation, acute dedifferentiated leukaemia cases were characterised by a lot of frequent mutations in PHF6 (5/15 vs 0/19, p = 0.016) and a lot of frequent expression of TDT on blasts (p = 0.003) whereas acute myelocytic leukemia with nominal differentiation cases had a lot of frequent CD123 [removed]p = 0.042). Outcome knowledge showed no distinction in overall survival, relapse free survival, or rates of complete remission between acute dedifferentiated leukemia and acute myelocytic leukemia with nominal differentiation teams (p > 0.05). Acute myelocytic leukemia with myelodysplasia-related changes patients showed shorter survival once censoring for bone marrow transplant as compared to acute dedifferentiated leukemia (p = 0.03) and acute myelocytic leukemia with nominal differentiation (p = 0.002). during this largest series so far, the acute dedifferentiated leukemia cluster shows distinct characteristics from acute myelocytic leukemia with nominal differentiation, as well as a lot of frequent PHF6 mutations and expression of TDT. [4]
AML with Additional Cytogenetic Abnormalities to t(8: 21) has Poorer Survival than that with Isolated t(8;21): A Retrospective Multicenter Cohort Study
Aim of the Study: to research the poor prognostic factors incriminated in AML with t (8; 21), notably further genetic science findings, clinicopathological presentation and their impact on survival rate in Egyptian and Saudi patients.
Study Design: Patients were collected from 3 centers: nine cases from King Abdullah Medical town in Makah, between 2010 and 2013, sixteen from King Fahad Medical town in capital of Saudi Arabia, Kingdom of Saudi Arabia between 2007 and 2013 and sixteen patients from National Cancer Institute, Cairo University, Egypt 2010 and 2013.
Methodology: we tend to studied forty one cases with t (8; 21). Immunophenotyping was performed victimisation BD- FACS System. standard karyotypic analysis was done victimisation normal culturing and stripe techniques. Clinicopathological and genetic science information were correlative with illness outcome.
Results: There was no statistically important distinction between Egyptian and Saudi patients regarding the medical specialty parameters or immunophenotype markers expression, Thirty four (82.9%) out of forty one patients achieved complete remission. The follow up amount for the full cluster ranged from two.1 to 170.3 weeks. The median survival was 146 weeks. the general survival rate was eightieth at one year and seventieth at 2 years. concerning the genetic science profile 33/41(80.5%) had isolated t(8;21) and eight patients (19.5%) had a chrosomal abnormality additionally to t(8;21); the most typical of that was + eight that was found in five patients. The median overall survival of these eight patients was twenty eight.4 compared to 146.7 weeks in cases with isolated t (8; 21) p=0.002. Also, they’d a lower one year overall survival rate (44%) than those with isolated t (8; 21) (86%) and their 2 years overall survival was zero.
Conclusion: AML related to further genetic science abnormalities to t (8;21) has poorer survival than that with isolated t(8;21). chromosomal aberration eight is generally incriminated for this being the foremost normally encountered during this study. [5]
Reference
[1] DiNardo, C.D., Pratz, K., Pullarkat, V., Jonas, B.A., Arellano, M., Becker, P.S., Frankfurt, O., Konopleva, M., Wei, A.H., Kantarjian, H.M. and Xu, T., 2019. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood, 133(1), pp.7-17. (Web Link)
[2] Lambert, J., Pautas, C., Terré, C., Raffoux, E., Turlure, P., Caillot, D., Legrand, O., Thomas, X., Gardin, C., Gogat-Marchant, K. and Rubin, S.D., 2019. Gemtuzumab ozogamicin for de novo acute myeloid
leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. haematologica, 104(1), pp.113-119. (Web Link)
[3] Cortes, J.E., Heidel, F.H., Hellmann, A., Fiedler, W., Smith, B.D., Robak, T., Montesinos, P., Pollyea, D.A., DesJardins, P., Ottmann, O. and Ma, W.W., 2019. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia, 33(2), p.379. (Web Link)
[4] Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group
Olga K. Weinberg, Robert P. Hasserjian, Ezra Baraban, Chi Young Ok, Julia T. Geyer, John K. S. S. Philip, Jason H. Kurzer, Heesun J. Rogers, Valentina Nardi, Richard M. Stone, Jacqueline S. Garcia, Eric D. Hsi, Adam Bagg, Sa A. Wang, Attilio Orazi & Daniel A. Arber
Modern Pathology (2019) (Web Link)
[5] Ahmad Bahgat Abdulateef, N., Mohammad Ismail, M., Aly Elmorsy, S., F. ALswayyed, A., Hamed Abdou, E. and Elemam, O. (2015) “AML with Additional Cytogenetic Abnormalities to t(8: 21) has Poorer Survival than that with Isolated t(8;21): A Retrospective Multicenter Cohort Study”, International Blood Research & Reviews, 3(1), pp. 36-46. doi: 10.9734/IBRR/2015/15529. (Web Link)