KEY TAKEAWAYS
- The phase 3 OCEAN study compared progression-free survival between melflufen and dexamethasone versus pomalidomide and dexamethasone in patients.
- The study was a randomized, open-label, head-to-head trial with patients divided into two groups using a 1:1 ratio and stratified by age and number of prior lines of therapy.
- The study’s primary outcome was progression-free survival as determined by an external review committee.
- The most common treatment-emergent side effects observed were thrombocytopenia, neutropenia, and anemia.
- The study concluded that melflufen plus dexamethasone showed tolerable safety and clinical activity, resulting in a longer median overall survival than pomalidomide.
Clinical activity and tolerable safety were observed in a phase 2 HORIZON study of melphalan sulfenamide (melflufen), an alkylating peptide-drug conjugate, combined with dexamethasone. Investigators wanted to see if melflufen plus dexamethasone would improve progression-free survival (PFS) compared to pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. Adult patients (aged 18 years) were recruited from 108 university hospitals, specialized hospitals, and community-based centers in 21 countries across Europe, North America, and Asia for this randomized, open-label, head-to-head, phase 3 trial (OCEAN). Eligible patients received two to four prior lines of therapy (including lenalidomide and a proteasome inhibitor), had an ECOG performance status of 0-2, and had relapsed or refractory multiple myeloma within 18 months of randomization. Patients were divided into two groups, one receiving melflufen and dexamethasone for 28 days (melflufen group) and the other receiving pomalidomide and dexamethasone for 28 days (pomalidomide group), using a 1:1 ratio that was stratified by age, number of prior lines of therapy, and International Staging System score. On days 1, 8, 15, and 22 of each cycle, all patients were given 40 mg of oral dexamethasone. Patients in the melflufen group got 40 mg of melflufen IV over 30 minutes on cycle day 1, while those in the pomalidomide group took 4 mg of pomalidomide orally, once daily, from cycle day 1 through cycle day 21. In the ITT population, progression-free survival, as determined by an external review committee, was the primary outcome. Patient safety was evaluated in those who took at least one dosage of the trial drug.
A total of 246 patients (median age 68 [IQR 60-72], 107 [43%] were female) and 259 patients (median age 68 [IQR 61-72], 109 [44%] were female) were randomly allocated to the melflufen group between June 12, 2017, and September 3, 2020. All the 474 individuals received at least one dosage of study medication (228 in the melflufen group and 246 in the pomalidomide group, making up the safety population). After a median of 19 months of treatment with melflufen (IQR 12 months to 25 months) and 18 months of therapy with pomalidomide (IQR 11 months to 23 months), the melflufen group had a median overall survival of 19 months (95% confidence interval [CI] 15 months to 25 months; p=047). Thrombocytopenia (143 [63%] of 228 in the melflufen group vs. 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs. 102 [41%]), and anemia (97 [43%] vs. 44 [18%]) were the most common treatment-emergent side events. A total of 95 patients in the melflufen group (42%) and 113 in the pomalidomide group (46%) experienced severe treatment-emergent adverse events. The most prevalent of these were pneumonia (13% vs. 21%, respectively), COVID-19 pneumonia (11% vs. 4%), and thrombocytopenia (9% vs. 1%). Treatment-emergent adverse events were responsible for the deaths of 27 patients (12%) on melflufen and 32 patients (13%) on pomalidomide. Two patients in the melflufen group (one with acute myeloid leukemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two with pneumonia, one with pneumonia, one with myelodysplastic syndromes, and one with COVID-19 pneumonia) experienced fatal treatment-emergent adverse events that were possibly treatment-related.
Source:https://pubmed.ncbi.nlm.nih.gov/35032434/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03151811
Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Špička I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosiñol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hájek R, Mateos MV, Richardson PG, Sonneveld P; OCEAN (OP-103) Investigators. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomized, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022 Feb;9(2):e98-e110. doi: 10.1016/S2352-3026(21)00381-1. Epub 2022 Jan 12. PMID: 35032434.
