Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000

Kantarjian, Hagop M.; DiNardo, Courtney D.; Nogueras‐González, Graciela M.; Kadia, Tapan M.; Jabbour, Elias; Bueso‐Ramos, Carlos E.; O’Brien, Susan; Konopleva, Marina; Jain, Nitin; Daver, Naval; Shpall, Elizabeth J.; Champlin, Richard E.; Simkins, Aron; Keating, Michael J.; Huang, Xuelin; Cortes, Jorge; Pierce, Sherry; Ravandi, Farhad; Freireich, Emil J.

doi:10.1002/cncr.31370

Cited by 23 publications

(24 citation statements)

References 17 publications

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“…Our interpretation of the effect of treatment on disease free survival and OS was limited by the small sample size estimates and short follow-up time. Nevertheless, the survival data in our study compared favorably to historical OS estimates of 5.9 and 4.7 months in first- and second- salvage AML, respectively ( 54 , 55 ). In this context, survival in R/R AML is highly influenced by the post-remission therapy, ASCT being the only consistently curative option with patients rarely achieving durable remissions with non-transplant strategies ( 56 ).…”

Section: Discussionsupporting

confidence: 54%

Initial Report of a Phase I Study of LY2510924, Idarubicin, and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

et al. 2018

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Background: The CXCR4/SDF-1α axis plays a vital role in the retention of stem cells within the bone marrow and downstream activation of cell survival signaling pathways. LY2510924, a second generation CXCR4, showed significant anti-leukemia activity in a murine AML model.Methods: We conducted a phase I study to determine the safety and toxicity of LY2510924, idarubicin and cytarabine (IA) combination therapy in relapsed/refractory (R/R) AML. Eligible patients were 18–70 years of age receiving up to salvage 3 therapy. A peripheral blood absolute blast count of < 20,000/μL was required for inclusion. LY2510924 was administered daily for 7 days followed by IA from day 8. Two dose escalation levels (10 and 20 mg) were evaluated, with a plan to enroll up to 12 patients in the phase I portion.Results: The median age of the enrolled patients (n = 11) was 55 years (range, 19–70). Median number of prior therapies was 1 (1–3). Six and five patients were treated at dose-levels “0” (10 mg) and “1” (20 mg), respectively. Only one patient experiencing a dose limiting toxicity (grade 3 rash and myelosuppression). Three and one complete responses were observed at dose-levels “0” and “1,” respectively; the overall response rate (ORR) was 36% (4 of 11 patients). A ≥ 50% decrease in CXCR4 mean fluorescence intensity was observed in 4 of 9 patients by flow cytometry, indicating incomplete suppression of CXCR4-receptor occupancy.Conclusions: The combination of LY2510924 with IA is safe in R/R AML. Dose-escalation to a 30 mg LY2510924 dose is planned to achieve complete blockade of CXCR4 receptor occupancy, followed by expansion phase at the recommended phase 2 dose-level.

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Section: Discussionsupporting

confidence: 54%

Initial Report of a Phase I Study of LY2510924, Idarubicin, and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

et al. 2018

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“…This is comparable to the 19% CR/CRi observed with single-agent venetoclax [60]. Hence, with the data available, the value of venetoclax as a salvage therapy either alone or in combination with HMAs/LDAC appears comparable with standard salvage regimens [77].…”

Section: Targeting Bcl-2 In Amlsupporting

confidence: 52%

Targeting Apoptotic Pathways in Acute Myeloid Leukaemia

Sillar

Enjeti

2019

Cancers

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Acute Myeloid Leukaemia is a devastating disease that continues to have a poor outcome for the majority of patients. In recent years, however, a number of drugs have received FDA approval, following on from successful clinical trial results. This parallels the characterization of the molecular landscape of Acute Myeloid Leukaemia (AML) over the last decade, which has led to the development of drugs targeting newly identified recurring mutations. In addition, basic biological research into the pathobiology of AML has identified aberrant programmed cell death pathways in AML. Following on from successful outcomes in lymphoid malignancies, drugs targeting the B Cell Lymphoma 2 (BCL-2) family of anti-apoptotic proteins have been explored in AML. In this review, we will outline the preclinical and clinical work to date supporting the role of drugs targeting BCL-2, with Venetoclax being the most advanced to date. We will also highlight rationale combinations using Venetoclax, ongoing clinical trials and biomarkers of response identified from the early phase clinical trials performed.

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“…In general, however repetition at relapse of the same induction and post‐remission therapy used initially leads to worse results This suggests that even should second CR be attained with standard induction, post‐remission therapy should, if feasible, include allo HCT, particularly if this has not been done before; indeed, regardless of prognostic group patients lived longer if in CR2 they received allo HCT, although, as usual, various selection biases may have affected the decision to perform allo HCT 150 . The recommendation for new therapy/clinical trials in all patients in the intermediate and, particularly worst, Breems et al prognostic groups certainly extends to older patients, who all else being equal would be expected to do even worse than the patients analyzed by Breems et al 151 and to all patients who are receiving a second re‐induction attempt after failing a first 152 …”

Section: Relapsed and Refractory Amlmentioning

confidence: 99%

“…Uproleselan disrupts adherence, putatively re‐sensitizing blasts to chemotherapy. A single‐arm trial of uproleselan added to MEC reported 156 a 45% CR/CRi rate and 12.8 month median survival in the 22 patients with >10% E‐selectin ligand expression vs 29% CR/CRi rate with 5.4 month median survival in the 14 patients with less expression; 79% of the former and 72% of the latter patients were in the Breems et al poor prognostic group or receiving at least second salvage suggesting results in the higher expression group were better than those otherwise expected 150,152 . A randomized trial comparing FAI or MEC +/− uproleselan is ongoing in relapsed/ refractory and newly‐diagnosed patients.…”

Section: Relapsed and Refractory Amlmentioning

confidence: 99%

Acute myeloid leukemia: 2021 update on risk‐stratification and management

Estey

2020

American J Hematol

115

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Management of AML involves choosing between purely palliative care, standard therapy and investigational therapy ("clinical trial"). Even most older patients likely benefit from treatment. Based on randomized trials CPX 351, midostaurin, gemtuzumab ozogamicin, and venetoclax, the latter three when combined with other drugs, should now be considered standard therapy. Knowledge of the likely results with these therapies is essential in deciding whether to recommend them or participate in a clinical trial, possibly including these drugs. Hence here, in the con

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Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000

Cited by 23 publications

References 17 publications

Initial Report of a Phase I Study of LY2510924, Idarubicin, and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Initial Report of a Phase I Study of LY2510924, Idarubicin, and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Targeting Apoptotic Pathways in Acute Myeloid Leukaemia

Acute myeloid leukemia: 2021 update on risk‐stratification and management

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