Multicenter comparison of high-dose cytarabine-based regimens versus liposomal daunorubicin and cytarabine (CPX-351) in patients with secondary acute myeloid leukemia

Benitez, Lydia; Perissinotti, Anthony J.; Rausch, Caitlin R.; Klaus, Jeff; Clark, Scott G.; Filtz, Michael R.; Ratermann, Kelley; Treptow, Carissa; Griffin, Shawn; Olson, Marissa; Crain, Mallory; Kadia, Tapan M.; Pettit, Kristen; Burke, Patrick W.; Bixby, Dale; Marini, Bernard L.

doi:10.1080/10428194.2021.1907378

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…Other real-world series have found a median OS with ven/aza ranging from 9.8 to 12.5 months 13,28,29 vs the 14.7 months seen in the VIALE-A study. 8 Similarly, several groups have reported their real-world experience with CPX-351 including national, multicenter efforts from France, 30 Germany, 31 and Italy, 32 as well as smaller single center studies, 33 with median OS ranging from 9 to 21 months, with 28% to 62% of patients going on to allogeneic stem cell transplant. Our national study shows similar results with differences in transplant rates likely accounting for variation in median survivals.…”

Section: Discussionmentioning

confidence: 99%

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

et al. 2022

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CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n=217) or ven/aza (n=439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received venetoclax/azacitidine. Ven/aza patients were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo AML. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based upon therapy (13 months for CPX-351 versus 11 months for ven/aza, HR 0.88, 95% CI 0.71-1.08, p = 0.22). Overall survival was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs. 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission prior to next cycle of therapy, was more than twice as long for CPX-351. In this large multi-center real word dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.

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Section: Discussionmentioning

confidence: 99%

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

et al. 2022

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“…A retrospective analysis comparing HIDAC and purine analogue–based regimens with CPX-351 in sAML, AML with MDS-related cytogenetics, and t-AML demonstrated similar OS in both cohorts. 62 A multicenter retrospective analysis recently compared outcomes of CPX-351 versus HMA-VEN in newly diagnosed AML; however, this was not restricted to the patient population investigated in the phase III CPX-351 trial. Median OS was higher in the CPX-351 group, but when controlling for rates of allo-HCT, survival was similar.…”

Section: Secondary Aml and Therapy-related Amlmentioning

confidence: 99%

The Cup Runneth Over: Treatment Strategies for Newly Diagnosed Acute Myeloid Leukemia

Cooperrider

Shukla

Nawas

et al. 2023

JCO Oncology Practice

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Since 2017, the number of agents for acute myeloid leukemia (AML) has rapidly expanded. Given the increased therapeutic options, better identification of high-risk subsets of AML and more refined approaches to patient fitness assessment, the decisions surrounding selection of intensive chemotherapy versus lower-intensity treatment have grown increasingly more nuanced. In this review, we present available data for both standard and investigational approaches in the initial treatment of AML using an intensive chemotherapy backbone or a lower-intensity approach. We summarize management strategies in newly diagnosed secondary AML, considerations around allogeneic stem-cell transplantation, and the role of maintenance therapy. Finally, we highlight important areas of future investigation and novel agents that may hold promise in combination with standard therapies.

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“…The overall survival in patients treated with CPX-351 compared with the patients treated with “7 + 3” scheme was significantly improved (9.07. vs 5.95 months, HR:0.7; 95% CI: 0.53–0.95). The study was conducted on the group of patients aged 60 to 75 years [ 77 ]. The phase 2 study of CPX-351 (NCT04269213) in patients aged 18–59 years of age is ongoing; participants for the study are still being recruited [ 78 ].…”

Section: Treatment Options In Secondary Amlmentioning

confidence: 99%

In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

Stefaniuk

Szymczyk

Podhorecka

2022

JCM

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Secondary acute myeloid leukemia can be divided into two categories: AML evolving from the antecedent hematological condition (AHD-AML) and therapy related AML (t-AML). AHD-AML can evolve from hematological conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, MDS/MPN overlap syndromes, Fanconi anemia, and aplastic anemia. Leukemic transformation occurs as a consequence of the clonal evolution—a process of the acquisition of mutations in clones, while previous mutations are also passed on, leading to somatic mutations accumulation. Compared de novo AML, secondary AML is generally associated with poorer response to chemotherapy and poorer prognosis. The therapeutic options for patients with s-AML have been confirmed to be limited, as s-AML has often been analyzed either both with de novo AML or completely excluded from clinical trials. The treatment of s-AML was not in any way different than de novo AML, until, that is, the introduction of CPX-351—liposomal daunorubicin and cytarabine. CPX-351 significantly improved the overall survival and progression free survival in elderly patients with s-AML. The only definitive treatment in s-AML at this time is allogeneic hematopoietic cell transplantation. A better understanding of the genetics and epigenetics of s-AML would allow us to determine precise biologic drivers leading to leukogenesis and thus help to apply a targeted treatment, improving prognosis.

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Multicenter comparison of high-dose cytarabine-based regimens versus liposomal daunorubicin and cytarabine (CPX-351) in patients with secondary acute myeloid leukemia

Cited by 10 publications

References 14 publications

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

The Cup Runneth Over: Treatment Strategies for Newly Diagnosed Acute Myeloid Leukemia

In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

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