OCEAN subgroup analysis: Melflufen in patients refractory to prior alkylators

Melphalan flufenamide (melflufen), a first-in-class alkylating peptide drug conjugate, plus dexamethasone was recently approved in Europe for the treatment of multiple myeloma after ≥3 prior lines of treatment. Approval was based on results from the phase II HORIZON (NCT02963493) and phase III OCEAN trial (NCT03151811). An increasing number of patients with multiple prior lines of therapy are becoming exposed to, or refractory to alkylators which may alter the efficacy of melflufen.

In response to this, Schjesvold et al.¹ published a post hoc analysis in European Journal of Haematology investigating the effects of refractoriness to standard dose prior alkylators on the effectiveness of melflufen + dexamethasone in a subset of patients enrolled in the OCEAN trial. We summarize the results below.

Study design¹

• Patients randomized 1:1 to receive melflufen + dexamethasone or pomalidomide + dexamethasone.
• The primary endpoint was progression-free survival.

Key findings¹

• N = 153
  • n = 78 (melflufen + dexamethasone)
  • n = 75 (pomalidomide + dexamethasone)
• Response rates in patients refractory to prior alkylators by treatment arm, prior autologous stem cell transplant status and type of alkylator received are listed in Figure 1.

ASCT, allogeneic stem cell transplant; OS, overall survival; ORR, overall response rate; PFS, progression-free survival; TTP, time to progression.
*Adapted from Schjesvold, et al.¹

• Treatment-emergent adverse event frequency was comparable between melflufen and pomalidomide treatment arms (99% vs 97%, respectively).
• Patients treated with melflufen experienced a higher frequency of dose modifications and dose reductions vs pomalidomide (76% vs 67% and 47% vs 14%, respectively)
• Patients treated with melflufen experienced higher rates of Grade 3/4 thrombocytopenia (73% vs 14%), neutropenia (65% vs 55%) and leukopenia (14% vs 3%) compared to pomalidomide.

Key learnings

Results show a consistent clinical benefit for melflufan + dexamethasone compared with pomalidomide + dexamethasone in patients who had received prior alkylator therapies. The analysis also provides further evidence that receiving previous alkylator treatment does not adversely impact the effectiveness of melflufan + dexamethasone. The possibility of switching to a therapy with a new mechanism of action such as melflufen after immunotherapy failure needs further investigation.