OCEAN and HORIZON Trials: More Benefit Than Risk With Melflufen Plus Dexamethasone in Myeloma?

By: Julia Fiederlein Cipriano, MS
Posted: Wednesday, November 29, 2023

The primary results of a phase III trial revealed significantly longer progression-free survival—but not overall survival—among patients with relapsed or refractory multiple myeloma who received dexamethasone plus the alkylating peptide drug-conjugate melphalan flufenamide (melflufen) vs pomalidomide. Pieter Sonneveld, MD, PhD, of Erasmus MC Cancer Institute, Rotterdam, the Netherlands, and colleagues thus conducted a post-hoc analysis of both the pivotal phase II HORIZON and aforementioned confirmatory OCEAN study to further assess the benefit-risk profile of this combination. Their findings, which were published in the journal Clinical Lymphoma, Myeloma & Leukemia, may also offer a perspective on the U.S. Food and Drug Administration’s safety alert for melflufen.

“[Our findings] demonstrate a consistent benefit for melflufen and dexamethasone in patients…who have not received an autologous stem cell transplantation [ASCT] or [whose disease] progressed more than 36 months after receiving an ASCT,” the investigators commented.

The OCEAN study identified age (P = .011; < 65 favoring pomalidomide) and having no prior ASCT or a remission duration of more than 36 months after the procedure (P = .001; favored melflufen) as prognostic factors for overall survival. A total of 49% of the randomly assigned patients underwent prior ASCT; of this population, 82% experienced disease progression within 36 months. After excluding the patients treated with melflufen (n = 145) and pomalidomide (n = 148) who experienced disease progression within 36 months of undergoing ASCT, the median durations of overall survival were 23.6 and 19.8 months, respectively (hazard ratio = 0.83; P = .22).

Among patients from the HORIZON study with triple-class–refractory disease, those who experienced disease progression within 36 months of undergoing ASCT (n = 58) were found to have a lower response rate, as well as shorter durations of response and progression-free survival, than the remainder of the population (n = 52). The safety profile of melflufen plus dexamethasone appeared to be congruent with previous reports.

Disclosure: For full disclosures of the study authors, visit clinical-lymphoma-myeloma-leukemia.com.

Clinical Lymphoma, Myeloma & Leukemia

---