CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia

Cafaro, Alessandro; Giannini, Maria Benedetta; Silimbani, Paolo; Cangini, Delia; Masini, Carla; Rorà, Andrea Ghelli Luserna di; Simonetti, Giorgia; Martinelli, Giovanni; Cerchione, Claudio

doi:10.23736/s0026-4806.20.07017-2

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…Liposomal reconstitution of drugs might confer new physicochemical features to the drug and improve the drug’s stability, solubility, delivery in vivo , and targeting . For example, CPX-351 (also known as Vyxeos), a liposomal encapsulated daunorubicin and cytarabine, has been used in acute myeloid leukemia treatment . As early as the 1980s, researchers constituted liposomal melphalan particles and investigated their distributions in vivo in experimental animals .…”

Section: Discussionmentioning

confidence: 99%

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity

Zheng

Chu

et al. 2022

ACS Omega

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Multiple myeloma (MM), a plasma cell cancer in bone marrow, remains an incurable disease. Melphalan, an alkylating agent, is a conventional anticancer drug that is still widely used for MM treatment in clinics. However, melphalaninduced organ toxicity and side effects are common. In this study, we loaded melphalan into a liposomal capsule and constituted liposomal melphalan (liposomal MEL). Liposomal MEL particles were approximately 120 nm in size and stable in vitro. The liposomal particles could be effectively taken up by MM cells. In vitro cytotoxicity assays using MM cell lines and primary MM cells showed that liposomal MEL exhibited similar anti-MM activity compared to an equivalent amount of free melphalan (free MEL) compound. In animal models, liposomal particles had bone marrow enrichment and prolonged half-life in vivo. Liposomal MEL exposure resulted in less liver and colon organ toxicity than exposure to an equivalent amount of free MEL-treated mice. Importantly, liposomal MEL had potent anti-MM activity in vivo in a human MM xenograft mouse model. Overall, our findings suggested that liposome-encapsulated melphalan was an effective drug modification of the melphalan compound and showed promise in MM treatment.

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Section: Discussionmentioning

confidence: 99%

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity

Zheng

Chu

et al. 2022

ACS Omega

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“…CPX-351 is a liposomal formulation with a 1:5 molecular ratio of daunorubicin and cytarabine that optimizes drug delivery, with preferential uptake by LSCs compared to normal HSCs [ 157 , 158 , 159 ].…”

Section: New Formulations Old Drugsmentioning

confidence: 99%

New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy

Andreozzi

Massaro

Wittnebel

et al. 2022

IJMS

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For decades, intensive chemotherapy (IC) has been considered the best therapeutic option for treating acute myeloid leukemia (AML), with no curative option available for patients who are not eligible for IC or who have had failed IC. Over the last few years, several new drugs have enriched the therapeutic arsenal of AML treatment for both fit and unfit patients, raising new opportunities but also new challenges. These include the already approved venetoclax, the IDH1/2 inhibitors enasidenib and ivosidenib, gemtuzumab ozogamicin, the liposomal daunorubicin/cytarabine formulation CPX-351, and oral azacitidine. Venetoclax, an anti BCL2-inhibitor, in combination with hypomethylating agents (HMAs), has markedly improved the management of unfit and elderly patients from the perspective of improved quality of life and better survival. Venetoclax is currently under investigation in combination with other old and new drugs in early phase trials. Recently developed drugs with different mechanisms of action and new technologies that have already been investigated in other settings (BiTE and CAR-T cells) are currently being explored in AML, and ongoing trials should determine promising agents, more synergic combinations, and better treatment strategies. Access to new drugs and inclusion in clinical trials should be strongly encouraged to provide scientific evidence and to define the future standard of treatment in AML.

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“… 153 Ratiometric delivery of drugs is based on the rationale that a combination of molar ratios of drugs can have synergistic action relative to using individual drugs at the maximum tolerable dose. 154 Vyxeos was developed with the idea that a fixed molar drug ratio of 5 : 1 packed in liposomal vesicles would provide better efficacy and tolerability to the drug administered historically by the standard 7 + 3 regimen. The proposed advantage of using a liposomal fixed molar ratio of the drug is highlighted in Fig.…”

Section: Future Outlookmentioning

confidence: 99%

“…Although the molar drug ratio of 5 : 1 shows maximum synergistic activity in vitro it is difficult to maintain in vivo ratiometry by traditional chemotherapy using iv infusion due to the difference in the pharmacokinetics of the two drugs which may eventually lead to an antagonistic dose ratio. 154 Liposomes at a lipid ratio of 7 : 2 : 1 of distearoylphosphatidylcholine (DSPC), distearylphosphatidylglycerol (DSPG), and cholesterol provide the requisite biophysical properties for homing the drug in the required 5 : 1 ratio to maintain the synergistic ratio for an extended duration that has been used to resolve the issue of delivering the synergistic combination to the target cells. 156 It is a non-PEGylated liposome that remains in a gel state at body temperature and provides the required in vivo stability.…”

Section: Future Outlookmentioning

confidence: 99%

Revisiting the outstanding questions in cancer nanomedicine with a future outlook

2022

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CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia

Cited by 11 publications

References 31 publications

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity

New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy

Revisiting the outstanding questions in cancer nanomedicine with a future outlook

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