PORT: A Randomized, Cross-Over, Phase 2 Study of Melflufen Peripheral Versus Central Intravenous Administration in Patients With Relapsed/Refractory Multiple Myeloma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00079838" target="_blank" >RIV/65269705:_____/24:00079838 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/24:73624775 RIV/00098892:_____/24:10158738

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2152265024000910?pes=vor" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2152265024000910?pes=vor</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.clml.2024.02.012" target="_blank" >10.1016/j.clml.2024.02.012</a>

Result language

angličtina

Original language name

PORT: A Randomized, Cross-Over, Phase 2 Study of Melflufen Peripheral Versus Central Intravenous Administration in Patients With Relapsed/Refractory Multiple Myeloma

Original language description

Melflufen infusion is given via central venous catheter (CVC); however, use of a peripheral venous catheter (PVC) may be preferable. This study provides data on pharmacokinetics, safety, and tolerability of PVC versus CVC melflufen administration. Melphalan exposure following PVC and CVC administration was bioequivalent; PVC administration was well tolerated, providing support for this route for melflufen administration in future studies. Background: Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered via central venous catheter (CVC). However, administration by peripheral venous catheter (PVC) may be preferable. Patients and Methods: PORT was a two-period, phase 2 crossover study of CVC versus PVC melflufen administration in patients with relapsed/refractory multiple myeloma. Adults with &gt;= 2 prior therapies refractory to/intolerant of an immunomodulatory drug and a proteasome inhibitor were randomized 1:1 to weekly oral dexamethasone plus melflufen (40 mg) via CVC or PVC infusion on day 1 of 28-day cycle 1. In cycle 2, patients continued dexamethasone and crossed over to the other melflufen administration route. In cycle 3, all patients received melflufen until progression; PVC or CVC routes were allowed based upon investigator decision. Pharmacokinetic sampling was performed during and after melflufen infusion. Primary endpoints were melphalan pharmacokinetic parameters (Cmax , AUC(0-t) , and AUC(0- infinity ) ) and frequency and severity of PVC-related local reactions. Results: The 90% CIs for adjusted geometric mean ratios for pharmacokinetic parameters following CVC versus PVC administration were within the 0.8-1.25 bioequivalence range (Cmax 0.946 [90% CI: 0.849, 1.053]; AUC(0-t) 0.952 [90% CI: 0.861, 1.053]; AUC(0- infinity ) 0.955 [90% CI: 0.863, 1.058]). In both arms, adverse events were pr imar ily hematological and similar; no phlebitis or local infusion-related reactions occurred. Conclusion: Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Clinical Lymphoma Myeloma &amp; Leukemia

ISSN

2152-2650

e-ISSN

2152-2669

Volume of the periodical

24

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

"e267"-"e275.e2"

UT code for WoS article

001249566600001

EID of the result in the Scopus database

2-s2.0-85187982904