scholarly journals Real-World Outcomes of Patients with Refractory or Relapsed FLT3-ITD Acute Myeloid Leukemia: A Toulouse-Bordeaux DATAML Registry Study

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2044
Author(s):  
Pierre-Yves Dumas ◽  
Sarah Bertoli ◽  
Emilie Bérard ◽  
Laetitia Largeaud ◽  
Audrey Bidet ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Real World ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Hypomethylating Agents ◽  
First Line ◽  
Phase 3 ◽  
Free Treatment ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Two recent phase 3 trials showed that outcomes for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) patients may be improved by a single-agent tyrosine kinase inhibitor (TKI) (i.e., quizartinib or gilteritinib). In the current study, we retrospectively investigated the characteristics and real-world outcomes of R/R FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) patients in the Toulouse-Bordeaux DATAML registry. In the study, we included 316 patients with FLT3-ITD AML that received intensive chemotherapy as a first-line treatment. The rate of complete remission (CR) or CR without hematological recovery (CRi) was 75.2%, and 160 patients were R/R after a first-line TKI-free treatment (n = 294). Within the subgroup of R/R patients that fulfilled the main criteria of the QUANTUM-R study, 48.9% received an intensive salvage regimen; none received hypomethylating agents or low-dose cytarabine. Among the R/R FLT3-ITD AML patients with CR1 durations < 6 months who received intensive TKI-free treatment, the rate of CR or CRi after salvage chemotherapy was 52.8%, and these results allowed a bridge to be transplanted in 39.6% of cases. Finally, in this QUANTUM-R standard arm-matched cohort, the median overall survival (OS) was 7.0 months and 1-, 3- and 5-year OS were 30.2%, 23.7% and 21.4%, respectively. To conclude, these real-world data show that the intensity of the second-line treatment likely affects response and transplantation rates. Furthermore, the results indicate that including patients with low-intensity regimens, such as low-dose cytarabine or hypomethylating agents, in the control arm of a phase 3 trial may be counterproductive and could compromise the results of the study.

scholarly journals TREATMENT WITH LOW-DOSE CYTARABINE IN ELDERLY PATIENTS (AGE 70 YEARS OR OLDER) WITH ACUTE MYELOID LEUKEMIA: A SINGLE INSTITUTION EXPERIENCE

2016 ◽  
Vol 8 ◽  
pp. 2016009 ◽  
Author(s):  
Maël Heiblig ◽  
Mohamed Elhamri ◽  
Isabelle Tigaud ◽  
Adriana Plesa ◽  
Fiorenza Barraco ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Single Institution ◽  
Low Dose Cytarabine ◽  
Acute Myeloid ◽  
Better Than

Objectives: Low-dose cytarabine (LD-AraC) is still regarded as the standard of care in elderly patients with acute myeloid leukemia (AML) ‘unfit’ for intensive chemotherapy. In this study, we compared the efficacy of LD-AraC, in patients ≥ 70 years old, with that of intensive chemotherapy, best supportive care (BSC), or hypomethylating agents in a single institution experience.Methods: Between 2000 and 2014, 60 patients received LD-AraC at 20 mg once or twice daily by subcutaneous injection for 10 consecutive days every 4-6 weeks. 85 patients were treated by intensive chemotherapy, 34 patients by hypomethylating agents, and 43 patients only by BSC.Results: Complete remission rate with LD-AraC was 7% versus 56% with intensive chemotherapy and 21% with hypomethylating agents. Median overall survival (OS) of patients treated with LD-AraC was 9.6 months with 3-year OS of 12%. Survival with LD-AraC was better than with BSC only (P = 0.001). Although not statistically significant, intensive chemotherapy and hypomethylating agents tended to be better than LD-AraC in terms of OS (median: 12.4 months and 16.1 months, respectively). There was no clear evidence that a beneficial effect of LD-AraC was restricted to any particular subtype of patients, except for cytogenetics.Conclusions: Despite a trend in favor of intensive chemotherapy and hypomethylating agents over LD-AraC, no real significant advantage could be demonstrated, while LD-AraC showed a significant advantage comparatively to BSC. This tends to confirm that LD-AraC can still represent a baseline against which new promising agents may be compared either alone or in combination.

scholarly journals First Description of Upfront Target Therapy Treating AML and Bcll Presented Simultaneously As First Line

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Juliana Santos Carvalho ◽  
Anna Flávia Silva Alves Silva ◽  
Maysa Coité Silva ◽  
Itala Gomes Santos ◽  
Laryssa Pinto Aragão ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Case Report ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Target Therapy ◽  
First Line ◽  
Hematological Neoplasms ◽  
Hla Dr ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

INTRODUCTION: The occurrence of acute myeloid leukemia (AML) and chronic lymphoid leukemia (B-CLL) simultaneously is rarely described. We describe a case report of AML and B-CLL, diagnosed simultaneously, without any previous treatment for any of the hematological neoplasms [1]. The patient received low-dose cytarabine (ARA-C) and Venetoclax, which is medically indicated on label for both hematological neoplasms. CASE REPORT: A 75-year-old male, presented with edema and joint pain one month before hospital admission, showing pancytopenia on a complete blood count and presence of blasts in peripheral blood. The patient was then referred to the hematology service. The morphological analysis of the bone marrow aspirate showed 67.7% of myeloblasts, compatible with AML. Bone marrow immunophenotyping was performed, which identified 34.10% of myeloblasts, compatible with AML and 50.48% of monoclonal B lymphocytes (chronic B-cell lymphoproliferative disease). In flow cytometry there were two distinct populations of myeloblasts. Type 1 myeloblasts labeling CD7 +, CD13 +, CD34 ++, CD38 ++, CD45 ++, CD56 ++, CD117 ++, CD123 +, HLA-DR +++ and MPO + / ++. The second population marked CD13 + / ++, CD34 + / ++, CD38 ++, CD45 +, CD117 ++, CD123 +, HLA-DR ++ / +++ and MPO + (30%). Monoclonal lymphocytes showed CD11c + / ++ (70%), CD19 ++, CD20 + / ++ (84%), CD22 + (39%), CD23 + / ++, CD25 +, CD31 +/-, CD43 ++, CD45 ++ / +++, CD81 + (38%), CD200 + (85%) and Lambda +. The molecular study was negative for genetic abnormalities: FLT3, KIT and NPM, configuring the patient as an intermediate risk for AML. In the cytogenetic analysis there was no growth of metaphases. Patient received simultaneous diagnosis of AML and B-CLL. As he was ineligle to intensive chemotherapy (IC), we started original protocol Subcutaneous Cytarabin+venetoclax(VIALE C). The patient had grade 2-3 AE(neutropenia managed with GCSF) ending the fourth cycle in July 2020. The evolution of hematimetric parameters and diseases are described in graphics. DISCUSSION: This is the first described case in our knowledge treated upfront with bcl2-inh target therapy for two absolutely different hematological neoplasms: AML and BCLL. Nowadays we are experiencing a new therapeutic model in oncohematology, in which the targeted therapy is gaining ground in relation to IC with excellent results. In this way, the importance of comprehension of the pathophysiological mechanism of the neoplasms and the way we can stop the disease proliferation is progressively guiding the new protocols. Elderly patients are more likely to have early treatment-related death and exhibit therapeutic resistance, limiting alternatives. We decided to start first-line treatment with ARA-C and Venetoclax [2]. Venetoclax associated with ARA-C has a manageable safety profile, producing quick and durable remissions in elderly people with AML ineligible for IC, as well as in B CLL, being the best therapeutic alternative for the case, in our opinion. Venetoclax belongs to a group of drugs called Bcl-2 inhibitors, an anti-apoptotic protein, which works by blocking this protein in the body, causing apoptosis of both neoplastic cells. The high rate of remission and low early mortality, combined with fast and durable remission, make Venetoclax and ARA-C a new and attractive treatment for the elderly [2]. In our case, the intention of the product in the first line was not B-CLL, but it would certainly be a good option for this profile of elderly patients. CONCLUSION: We report the first description of simultaneous diagnosis of AML and B CLL treated with a Bcl-2 inhibitor, demonstrating that antitumor mechanisms can be extremely effective in completely different diseases. We have a long way to go in the search for full knowledge of oncohematological diseases and targeted therapies. However, this case report shows that we are on the right track. References: 1. MUSSAED, Eman Al; OSMAN, Hani; ELYAMANY, Ghaleb. Simultaneous existence of acute myeloid leukemia and chronic lymphocytic leukemia: a case report.Bmc Cancer.Springer Science and Business Media LLC. http://dx.doi.org/10.1186/s12885-016-2780-5. 2. WEI, Andrew H.; et al. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: results from a phase ib/ii study.Journal Of Clinical Oncology, [S.L.], 20 maio 2019. American Society of Clinical Oncology (ASCO). http://dx.doi.org/10.1200/jco.18.01600. Figure Disclosures De Queiroz Crusoe: Janssen:Research Funding.

Complete Hematological Remission after Decitabine Treatment in a Patient with Congenital Agammaglobulinemia, FLT3- and TP53-Mutated Acute Myeloid Leukemia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vigna E ◽  
◽  
Caracciolo D ◽  
Martino E ◽  
Mendicino F ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Treatment Options ◽  
Single Agent ◽  
Response Duration ◽  
Hypomethylating Agents ◽  
Unfit Patients ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Older and unfit patients with Acute Myeloid Leukemia (AML), which are uneligible for standard induction therapy, have limited treatment options. The therapeutic approach in these cases is based on the use of hypomethylating agents, either decitabine or azacitidine, or Low-Dose Cytarabine (LDAC). However, despite the extensive use of these agents, there is no consensus regarding the extent of their efficacy, and clinical benefit deriving from their use is very modest. We present a case of FLT3- and TP53-mutated AML in an unfit patient with congenital agammaglobulinemia, responsive to single agent decitabine, with a response duration of over 20 months.

scholarly journals Venetoclax Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4421-4421
Author(s):  
Jasson Villarreal Hernandez ◽  
Maria Condom ◽  
Helena Pomares ◽  
Susana Vives ◽  
Rosa Coll ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Response Rate ◽  
Hematologic Toxicity ◽  
Hypomethylating Agents ◽  
Advisory Committees ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Abstract Introduction Venetoclax, a BCL-2 specific inhibitor, used in combination with azacitidine in patients with newly-diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy treatment, has shown high response rate and overall survival compared with azacitidine monotherapy (Di Nardo et al. N Engl J Med 2020; 383:617-629). Moreover, venetoclax in combination with hypomethylating agents or with low-dose cytarabine is being explored in other settings being frequently used in relapsed/refractory (R/R) AML. Aims: We performed a retrospective study of patients diagnosed with R/R AML receiving azacitidine combinations in the Catalan Institute of Oncology (ICO) in order to determine the efficacy and safety of the combination. Methods We analyze 35 patients diagnosed with R/R AML at 4 hospitals belonging to ICO in Spain, treated with venetoclax (400mg/24h; initial daily dose of 100mg with a 3-day ramp-up to target dose of 400mg) in combination with hypomethylating agents (azacitidine 75mg/m 2 or decitabine 20mg/m 2) or low-dose cytarabine (20mg/m 2) from May 2019 to Agost 2021. Event was defined as death, refractoriness to treatment or progressive disease. Results Median age was 72 years (range 44-82). Seventeen (43%) patients had high-risk AML according to ELN 2017. Five (14%) patients received venetoclax in combination with decitabine, 20 (57%) patients with azacitidine, and 10 (29%) patients with low-dose cytarabine. The median number of cycles received was 3 (range 1-25). Early mortality in the first 30 days was 5.7% (2 patients). Overall response rate (ORR) was 58%. Complete remission (CR) rate was 48% and 10% partial remission. Seventeen patients (43%) needed venetoclax dosage adjustments due to hematologic toxicity. Median time to response was 2 months. Four patients (10%) were transitioned to allogeneic stem cell transplantation. The median OS was 9.5 months (95% C.I. 2.6-16.2). Response to treatment after 3-4 cycles, discriminate two groups patients with an OS of 13.57 months in those patients who achieved CR or PR vs 2.1 months in non-responders (p&lt;0001). Thirteen patients died as a result of infection (8.2%), disease progression (4.1%), and bleeding (1.3%) Summary/Conclusions Our study showed that real-world experience of treating patients with R/R AML with venetoclax in combination with hypomethylating agents or low-dose cytarabine is feasible, well tolerated with a rapid and promising response rate and low toxicity profile. Moreover, rapid responses shown with the combination, allow us to identify those patients who may benefit from this approach. Figure 1 Figure 1. Disclosures Sureda: Mundipharma: Consultancy; Bluebird: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Support for attending meetings and/or travel; GSK: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau.

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