Improved progression-free survival was observed when treating patients with relapsed/refractory multiple myeloma with melphalan flufenamide plus dexamethasone compared with pomalidomide plus dexamethasone.
The combination of melphalan flufenamide (melflufen) plus dexamethasone was superior in improving progression-free survival (PFS) compared with pomalidomide plus dexamethasone for patients with relapsed/refractory multiple myeloma, according to results from the phase 3 OCEAN study (NCT03151811) published in Lancet Haematology.1
For patients in the melflufen group, the median PFS was 6.8 months (95% CI, 5.0-8.5) with 67% of patients experiencing an event compared with a median PFS of 4.9 months (95% CI, 4.2-5.7) in the pomalidomide group, with 76% of patients having an event (HR, 0.79; 95% CI, 0.64-0.98; P = .032). The median follow up was 15.5 months.
“The OCEAN results demonstrates that melflufen improves PFS for [patients with] lenalidomide [Revlimid]–refractory relapsed or refractory multiple myeloma who have received 2 to 4 prior lines of therapy,” Klaas Bakker, MD, PhD, executive vice president, and chief medical officer at Oncopeptides, said in a press release.2 “We believe that melflufen may become an important treatment option for patients with relapsed or refractory multiple myeloma. In that respect, the comprehensive data provide valuable insights to the pending European Medicines Agency´s review of melflufen for a potential European approval later this year.”
In order to be eligible, patients needed to be 18 years or older, have a diagnosis of multiple myeloma with documented disease progression, and undergone 2 to 4 previous lines of therapy that included lenalidomide and a proteasome inhibitor. Moreover, patients needed to be refractory to their last line of therapy and lenalidomide, which had to be administered within 18 months before randomization. An ECOG performance status of 0 to 2 with measurable disease was also needed.
Treatment was administered in 28-day cycles, with melflufen given at 40 mg as an intravenous infusion for 30 minutes on the first day of each cycle. Pomalidomide was given at 4 mg orally on days 1 to 21 of each cycle for patients in the pomalidomide group. Additionally, 40 mg of dexamethasone was given to patients in both groups on days 1, 8, 15, and 22 of each cycle.
The study’s primary end point was PFS assessed by independent review committee. Secondary end points included overall response rate (ORR), overall survival (OS), and safety.
A total of 495 patients were randomized 1:1 to either the melflufen group (n = 246) or pomalidomide group (n = 249). As of the February 3, 2021, cutoff date, 76% and 80% of patients in the melflufen and pomalidomide groups discontinued treatment, respectively.
The median patient age was 68 years in both groups, and all but 2 patients (n = 493) had disease refractory to lenalidomide. The majority of patients in the melflufen and pomalidomide groups were male (57% vs 56%), resided in Europe (73% vs 71%), were White (91% vs 89%), and had an ECOG performance status of 1 (53% vs 55%).
ORR in the melflufen group was 33% (95% CI, 27%-39%) compared with 27% (95% CI, 22%-33%) in the pomalidomide group (P = .16). Partial responses or better were seen in 80 patients and 67 patients in the melflufen and pomalidomide groups, respectively. More patients in the melflufen group achieved a complete response (3% vs 1%), a very good partial response (9% vs 7%), or a partial response (20% vs 18%) than the pomalidomide group.
After a median follow up of 19.8 months, investigators reported a median OS of 19.8 months (95% CI, 15.1-25.6) in the melflufen group at a median follow-up of 19.8 months compared with 25.0 months (95% CI, 18.1-31.9) in the pomalidomide group at a median follow-up of 18.6 months (HR, 1.10; 95% CI, 0.85-1.44; P = .47).
The median duration of treatment in the melflufen group was 5.8 months vs 5.1 months in the pomalidomide group. Common grade 3/4 hematological adverse effects (AEs) in both themelflufen and pomalidomide groups, respectively, included neutropenia (54% vs 41%), thrombocytopenia (63% vs 11%), and anemia (43% vs 18%). Additionally, common grade 3/4 treatment-emergent AEs (TEAEs) in the melflufen and pomalidomide groups included thrombocytopenia (61% vs 9%), neutropenia (54% vs 39%), and anemia (38% vs 10%).
“We found that melflufen plus dexamethasone improves progression-free survival for patients with lenalidomide-refractory relapsed or refractory multiple myeloma. Whether the treatment combination is beneficial for those who have not received a previous autologous [hematopoietic stem-cell transplantation needs to be investigated further,” the investigators concluded.