Study of Vorinostat (MK0683), an Histone Deacetylase (HDAC) Inhibitor in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (MK-0683-095)

Objective RR was defined as percentage (%) of participants with complete response (CR: disappearance of original monoclonal (M) paraprotein from blood & urine on at least 2 determinations for at least 6 weeks (WKs) by immunofixation studies, <5% plasma cells in bone marrow on at least 1 determination, no increase in size/number of lytic bone lesions (LBLs) & disappearance of soft tissue plasmacytomas (STP) for at least 6 WKs on skeletal survey (SS) if available) or partial response (PR: ≥50% reduction in serum M protein for at least 2 determinations 6 WKs apart, if present, reduction in 24-hour urinary light chain excretion by ≥90% or ≤200 mg for at least 2 determinations 6 WKs apart, ≥50% reduction in STP size for at least 6 WKs, & no increase in size/number of LBLs on SS if available) as assessed by Independent Adjudication Committee (IAC) per European Blood & Marrow Transplant (EBMT) criteria. To report RR & 95% confidence intervals (CIs), exact test of binomial parameter was used.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE were reported.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE were reported.

TTP was defined as the time from allocation to the first documented disease progression (PD) as determined by IAC per EBMT criteria or death due to myeloma, whichever occurred first. PD: >25% increase in level of serum Mparaprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10% or definitive increase in size of existing LBLs or STP or development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause). To report the median TTP (in months) and associated 95% CIs Kaplan-Meier method was used.

TTP was defined as the time from allocation to the first documented PD as assessed by investigator per EBMT criteria or death due to myeloma, whichever occurred first. PD: >25% increase in level of serum Mparaprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10% or definitive increase in size of existing LBLs or STP or development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause). To report the median TTP (in months) and associated 95% CIs Kaplan-Meier method was used.

PFS was defined as the time from allocation to the first documents PD as determined by IAC per EBMT criteria or death due to any cause, whichever occurs first. PD: >25% increase in level of serum M-paraprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10% or definitive increase in size of existing LBLs or STP or development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause). To report the median PFS (in months) and associated 95%CIs Kaplan-Meier method was used.

PFS was defined as the time from allocation to the first documents PD as assessed by investigator per EBMT criteria or death due to any cause, whichever occurs first. PD: >25% increase in level of serum M-paraprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10% or definitive increase in size of existing LBLs or STP or development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause). To report the median PFS (in months) and associated 95%CIs Kaplan-Meier method was used.

OS was defined as the time from allocation to death due to any cause. To report the median survival (in months) and the associated 95%CIs were reported using Kaplan-Meier method was used. Participants without documented death at the time of final analysis were censored at the date of the last follow up.