O-12-M1: AN EVALUATION OF TIME TO NEXT TREATMENT IN MELFLUFEN AND DEXAMETHASONE-TREATED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Author(s): ,
Sara Bringhen
Affiliations:
Division of Hematology, University of Torino,Torino,Italy
,
Paul G. Richardson
Affiliations:
Dana-Farber Cancer Institute, Harvard Medical School,Boston,United States
,
Peter Voorhees
Affiliations:
Levine Cancer Institute, Carolinas HealthCare System,Charlotte,United States
,
Torben Plesner
Affiliations:
Department of Hematology, Vejle Hospital,Vejle,Denmark
,
Ulf-Henrik Mellqvist
Affiliations:
Borås Hospital,Borås,Sweden
,
Jeffrey A. Zonder
Affiliations:
Karmanos Cancer Institute, Wayne State University,Detroit,United States
,
Brandi Reeves
Affiliations:
Lineberger Comprehensive Cancer Center, University of North Carolina,Chapel Hill,United States
,
Stojan Zavisic
Affiliations:
Oncopeptides AB,Stockholm,Sweden
,
Johan Harmenberg
Affiliations:
Oncopeptides AB,Stockholm,Sweden
,
Jakob Obermüller
Affiliations:
Oncopeptides AB,Stockholm,Sweden
Pieter Sonneveld
Affiliations:
Erasmus Medical Center Rotterdam,Rotterdam,Netherlands
EHA Library. Bringhen S. 06/14/19; 266427; PF628
Dr. Sara Bringhen
Dr. Sara Bringhen
Contributions
Abstract

Abstract: PF628

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

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%).

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).

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Imids, Multiple myeloma, Phase I/II, Proteasome inhibitor

Abstract: PF628

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

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%).

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).

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Imids, Multiple myeloma, Phase I/II, Proteasome inhibitor

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies