PF628 O‐12‐M1: AN EVALUATION OF TIME TO NEXT TREATMENT IN MELFLUFEN AND DEXAMETHASONE‐TREATED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

• Published in: HemaSphere Vol. 3; no. S1; pp. 267 - n/a
• Main Authors: Bringhen, S., Richardson, P.G., Voorhees, P., Plesner, T., Mellqvist, U.‐H., Zonder, J.A., Reeves, B., Zavisic, S., Harmenberg, J., Obermüller, J., Sonneveld, P.
• Format: Journal Article
• Language: English
• Published: 01.06.2019
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/01.HS9.0000560796.93881.5c

Background: Melflufen is a novel peptide‐conjugated alkylator potentiated by intracellular aminopeptidases, which are markedly overexpressed in multiple myeloma. Melflufen plus dexamethasone had encouraging activity in patients with relapsed/refractory multiple myeloma and ≥2 prior lines of therapy in the phase 1/2 O‐12‐M1 study (overall response rate, 31%; median overall survival, 20.7 months; Richardson et al. ASH 2017. Abs. 3150). Time to next treatment is used in real world evidence to assist treatment decisions and support economic reimbursement modeling. Aims: To present a time to next treatment analysis of melflufen plus low‐dose dexamethasone in relapsed/refractory multiple myeloma patients exposed to bortezomib and lenalidomide in O‐12‐M1 (NCT01897714) and how it compares to recently reported relapsed/refractory multiple myeloma studies. Methods: Patients with relapsed/refractory multiple myeloma and ≥2 prior lines of therapy, including bortezomib and lenalidomide received 40 mg melflufen intravenously on day 1 of each 28‐day cycle plus 40 mg weekly dexamethasone until progressive disease or unacceptable toxicity. Patients were followed up for 2 years after PD, and time to next treatment was retrospectively reviewed for subsequent therapy. Results: As of 9 Nov 2017, 45 patients were treated: median age, 66 years (range, 47–78 years); International Staging System stage II/III, 60%; high‐risk cytogenetics, 44%. Patients had 4 median prior lines of therapy; 87% were refractory to last line of therapy including alkylators (24%), proteasome inhibitors (27%), IMiDs (56%), and monoclonal antibodies (9%); 11% were last‐line double refractory. At data cutoff, 44 patients (98%) discontinued melflufen plus dexamethasone, mainly due to adverse events (40%) and progressive disease (29%). Twenty‐six patients received subsequent therapy. Median time from start of melflufen plus dexamethasone to first subsequent therapy or death, whichever occurred first, (time to next treatment) was 7.9 months (95% CI, 5.7–11.0); next therapy included alkylators (27%), proteasome inhibitors (38%), IMiDs (58%), and monoclonal antibodies (8%). Summary/Conclusion: Types of subsequent salvage therapy used after melflufen plus dexamethasone were similar to studies of approved agents in relapsed/refractory multiple myeloma; time to next treatment was also similar (Table). Further trials are ongoing, including a phase 3 study of melflufen plus dexamethasone vs pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma refractory to lenalidomide (NCT03151811).