Mitoxantrone, Cytosine Arabinoside, and VP-16 in 36 Patients with Relapsed and Refractory Acute Myeloid Leukemia

Freund, M.; Diedrich, Helmut; Wilke, H.; Austein, J.; Henke, Michael; Wandt, Hannes; Fackler-Schwalbe, E.; Schlimok, G.; Hoffmann, Rüdiger; Calavrezos, A; Poliwoda, H.

doi:10.1007/978-3-642-74643-7_60

Cited by 12 publications

(9 citation statements)

References 3 publications

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“…Accordingly, in our cohort, most patients, and particularly those who had achieved CR, received an allo‐SCT, thus confirming the strong indication for allo‐SCT in 2nd CR 2,10 . Interestingly, transplant rate is higher than that observed in other studies, 27‐29,31,34‐37 which was likely due to the rise in transplantable age in most recent years, the relatively low age of our population and the usage of reduced intensity conditioning in older and intermediate fit patients. The high transplant rate should be also due to the low HCT‐CI score observed in our cohort.…”

Section: Discussionsupporting

confidence: 83%

“…The high transplant rate should be also due to the low HCT‐CI score observed in our cohort. In this context, the significant capacity of MEC to (re)induce CR in our patients’ population, coupled with the abovementioned increased propensity to allo‐SCT, even in the elderly population, translated into an OS slightly better than that reported in previous experiences 27‐29,31,34‐37 . Of note, approximately one out of five patients became long‐term survivor after MEC rescue.…”

Section: Discussionmentioning

confidence: 60%

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MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

Marconi

Talami

Abbenante

et al. 2020

European J of Haematology

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Introduction Clinical response and chemosensitivity of relapse or refractory AML patients were evaluated after rescue and bridge‐to‐transplant MEC (mitoxantrone, etoposide, and cytarabine) regimen. Methods and Patients Fifty‐five consecutive AML patients were treated with MEC from 2009 to 2018. Chemosensitivity was evaluated by WT1 quantification. Results 27/55 patients (49.1%) had AML resistant to induction and 28/55 patients (50.9%) had AML relapse. 25/55 patients (45.5%) achieved a CR after one course of MEC, and 12 patients (21.8%) achieved WT1 negativity. In 12 patients, a second MEC was administered. Four out of 12 patients improved significantly their response with the 2nd MEC. MEC was an effective bridge to transplant, 32/55 patients (58.2%) received an allogenic stem cell transplant. Median overall survival (OS) from MEC was 455 days (95% CI 307‐602 days.); patient with WT1 negative CR had the best OS (P<.000). Conclusion WT1 is a useful marker of chemosensitivity after MEC as rescue and bridge‐to‐transplant therapy.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 60%

MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

Marconi

Talami

Abbenante

et al. 2020

European J of Haematology

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“…MEC/EMA-86/MAV—Combinations of mitoxantrone, etoposide and cytarabine have been extensively evaluated in relapsed AML with multiple variations in the dose and schedule (MEC, EMA-86, MAV), resulting in CR rates between 18% and 66% [ 20 , 22 , 23 , 24 , 25 , 27 , 28 , 93 ] ( Table 1 ) with the highest rates seen when given as timed-sequential therapy [ 27 , 93 ]. A single-institution retrospective review by Price et al evaluated 162 patients with RR-AML treated with CLAG versus MEC and found overall CR rates of 37.9% versus 23.8% ( p = 0.05), with a median follow up of 20.3 months [ 20 ].…”

Section: Cytotoxic Chemotherapymentioning

confidence: 99%

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

Ramos

Karp

et al. 2015

JCM

103

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The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial.

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“…The outcome of patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor, with a median overall survival (OS) of <1 year and a long‐term survival rate of 5% to 20% . For patients undergoing re‐induction chemotherapy for R/R AML, several regimens, including the combination of mitoxantrone, etoposide, and cytarabine (MEC), have been evaluated and are used conventionally. In contemporary studies, the complete remission (CR) rate of MEC has been approximately 16% to 28% .…”

Section: Introductionmentioning

confidence: 99%

A phase 1 study of the antibody‐drug conjugate brentuximab vedotin with re‐induction chemotherapy in patients with CD30‐expressing relapsed/refractory acute myeloid leukemia

Narayan

Blonquist

Emadi

et al. 2019

Cancer

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Background Outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) remain poor. Novel therapies specifically targeting AML are of high interest. Brentuximab vedotin (BV) is an antibody‐drug conjugate that is specific for human CD30. In this phase 1 dose escalation study, the authors evaluated the safety of BV combined with mitoxantrone, etoposide, and cytarabine (MEC) re‐induction chemotherapy for patients with CD30‐expressing R/R AML. Methods Using a standard dose escalation design, the authors evaluated 3 dose levels of BV (0.9 mg/kg, 1.2 mg/kg, and 1.8 mg/kg) administered once on day 1 followed by MEC on days 3 through 7. Results There were no dose‐limiting toxicities noted and the maximum tolerated dose was not reached. The recommended phase 2 dose of BV was determined to be 1.8 mg/kg when combined with MEC. The side effect profile was similar to that expected from MEC chemotherapy alone, with the most common grade ≥3 toxicities being febrile neutropenia, thrombocytopenia, and anemia (toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Among the 22 patients enrolled on the trial, the composite response rate was 36%, with a composite response rate of 42% noted among those who received the highest dose of BV. The median overall survival was 9.5 months, with a median disease‐free survival of 6.8 months observed among responders. Approximately 55% of patients were able to proceed with either allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion. Conclusions The combination of BV with MEC was found to be safe in patients with CD30‐expressing R/R AML and warrants further study comparing this combination with the use of MEC alone in this population (ClinicalTrials.gov identifier NCT01830777). Lay summary The outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) are exceptionally poor. New and emerging treatment combinations are actively being studied in an effort to improve outcomes. The authors examined the combination of brentuximab vedotin, an antibody product that recognizes a marker called CD30, with mitoxantrone, etoposide, and cytarabine (MEC), a common chemotherapy regimen, in patients with R/R AML that expressed the CD30 marker. The authors found that the combination was safe and well tolerated. Future studies comparing this new combination with the use of MEC alone can help to inform its effectiveness for this patient population.

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Mitoxantrone, Cytosine Arabinoside, and VP-16 in 36 Patients with Relapsed and Refractory Acute Myeloid Leukemia

Cited by 12 publications

References 3 publications

MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

A phase 1 study of the antibody‐drug conjugate brentuximab vedotin with re‐induction chemotherapy in patients with CD30‐expressing relapsed/refractory acute myeloid leukemia

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