A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; \<5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein \<100 mg/24 h; If only FLC disease, \>90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to \<200 mg/24 h; other special cases if M-protein unmeasurable

Time frame: Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time to response in study recorded as 15.3 months. Longest time on treatment 35 months.

The clinical benefit rate (CBR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, PR, or MR as their best response as assessed by the investigator. See Primary Outcome (ORR) for definitions of response categories.

Time frame: Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study treatment recorded as 35.0 months at study end.

Time from first response to progression based on investigator assessment. See definitions of response and progression in ORR and PFS outcomes.

Time frame: From date of response until the date of first documented progression or date of death from any cause, whichever came first. Longest time of response recorded as 36.2 months at study end.

Population: Patients with a best response of PR or better as determined by the investigator.

Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales, 1 Global Health Status scale, 3 symptom scales, and 6 single items. The recall period is 1 week (the past week). The scales are transformed to a 0 (worst) to 100 (best) scale. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better HRQoL. If at least 50% of the items from the scale had been answered, the missing items were assumed to have values equal to the average of those items which were present for that respondent.

Time frame: To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.

Population: This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease.~62 pts in the FAS included after QoL was added in Amd 4, whereof 48 pts in the sub-group of pts with TCR disease.~This outcome measure was not analyzed/reported separately for the sub-group of patients with EMD as there were limited no. of pts with EMD among the QoL patients. No data/results are available to report for patients with EMD.

Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L. The EQ-5D-3L questionnaire converts 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression of patient-reported, current-day health status into a health utility score. For the EQ-5D-3L questionnaire, each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, no problems, some problems, and extreme problems, respectively. The EQ VAS scores rates health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No imputation of missing items or composite scores were done. The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual.

Time frame: To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.

Population: This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease.~62 pts in the FAS included after QoL was added in Amd 4, whereof 48 pts in the sub-group of pts with TCR disease.~This outcome measure was not analyzed/reported separately for the sub-group of patients with EMD as there were limited no. of pts with EMD among the QoL patients. No data/results are available to report for patients with EMD.

Time from start of treatment to death

Time frame: From date of first dose of study medication until the date of death from any cause, assessed up to 24 months after study drug discontinuation.

Population: Full Analysis Set.

Time from start of treatment to either progression or death, whichever comes first as assessed by the investigator using IMWG criteria. Progression of disease is defined by an increase of 25% from the lowest response for either of Serum M-component (absolute increase of ≥ 0.5 g/dL) or Urine M-component (absolute increase of ≥200 mg/ 24h); In patients without measurable M-protein a 25% increase in the difference between involved and uninvolved FLC (free light chain) levels (absolute increase must be \>10 mg/dL); If unmeasurable FLC levels, a 25% increase in bone marrow plasma cell percentage (absolute percentage must be \>10%); New bone or soft tissue plasmacytomas or definite increase in existing ones; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder

Time frame: Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest follow-up time for PFS recorded as 37.2 months at study end.

Population: Full analysis set

Duration from start of treatment to first evidence of disease progression as assessed by the investigator. See definitions of response and progression in ORR and PFS outcomes.

Time frame: From start of treatment to first evidence of disease progression or date of death from any cause, whichever came first. Longest time to progression recorded was 37.2 months at study end.

Population: This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease.~This outcome measure was analyzed/reported for patients in the full analysis set as well as in the sub-group of patients with triple class refractory disease.~This outcome measure was not analyzed/reported separately for the sub-group of patients with Extramedullary Disease. No data available to report for EMD patients.

Duration from start of treatment to the first occurrence of a confirmed response of PR or better as assessed by the investigator. See definitions of response in Primary Outcome (ORR).

Time frame: From start of treatment to first confirmed response. Longest time to response in study recorded as 15.3 months.

Population: This outcome measure was pre-specified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease.~This outcome measure was analyzed/reported for patients with a best response of PR or better in the full analysis set as well as in the sub-group of patients with triple class refractory disease.~This outcome measure was not analyzed/reported separately for the sub-group of patients with Extramedullary Disease. No data available to report for EMD patients.