Bortezomib (Velcade) in Patients With Untreated Multiple Myeloma

Objective response was defined as complete response (CR) or partial response (PR) according to European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). CR required all of the following: Negative immunofixation on the serum and urine at two consecutive times for minimum 6 weeks; Disappearance of soft tissue plasmacytomas for at least 6 weeks; \<5% plasma cells in bone marrow on 2 determinations for a minimum of 6 weeks; No increase in the size or number of lytic bone lesions. PR required all the following: ≥50% reduction in the level of the serum monoclonal protein on 2 determinations for minimum 6 weeks; If present, reduction in 24-hour urinary light chain excretion either by ≥90% or to \<200 mg on 2 determinations for minimum 6 weeks; ≥50% reduction size of soft tissue plasmacytomas for minimum 6 weeks; No increase in the number or size of lytic bone lesions. Development of a compression fracture does not exclude response in either category.

Time frame: Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Population: The analysis population is comprised of eligible and treated participants.

Number of participants experiencing any grade treatment-emergent neuropathic pain events based on CTCAEv3 as reported on case report forms.

Time frame: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Population: The analysis population is comprised of eligible and treated participants.

Number of participants experiencing any grade treatment-emergent sensory neuropathy events based on CTCAEv3 as reported on case report forms.

Time frame: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Population: The analysis population is comprised of eligible and treated participants.

PFS based on the Kaplan-Meier method is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD were censored at the earliest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: \>25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); \>25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); \>25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing soft tissue plasmacytomas and/or lytic lesions or new; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL not attributable to other cause).

Time frame: Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months as of the data analysis.

Population: The analysis population is comprised of eligible and treated participants.

TTP based on the Kaplan-Meier method is defined as the time from start of treatment to documentation of disease progression (PD). Participants without evidence of PD were censored at the latest date of last disease assessment or date of initiation of non-protocol therapy. PD was established based European Group for Blood and Marrow Transplantation criteria (Blade J et al Br J Haematol 1998). PD required 1 or more of the following: \>25% increase in serum monoclonal protein with absolute minimum of 0.5 g/dL (confirmed on repeat investigation); \>25% increase in 24-hour urinary light chain excretion with minimum absolute increase of 200 mg/24 hrs (confirmed on repeat investigation); \>25% increase in bone marrow plasma cells with minimum absolute increase of 10%; Definite increase in size of existing or new soft tissue plasmacytomas and/or lytic lesions; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL not attributable to other cause).

Time frame: Disease was assessed every two cycles on treatment and every 6 weeks in long-term follow-up. Median follow-up was 29 months.

Population: The analysis population is comprised of eligible and treated participants.

Very good partial response or better was defined per International Uniform Response criteria (Durie B, Harousseau JL, Miquel JS, et al Leukemia 2006). See CR requirements in primary outcome measure plus if serum and urine M protein were unmeasurable then immunoglobulin free light chain (FLC) must be in a normal ratio of 0.26-1.65 at two consecutive times. VGPR required the following: Serum and urine M-component detectable by immunofixation but not on electrophoresis; \>=90% reduction in serum M-component plus urine M-component \<100 mg per 24 hours (by SPEP and UPEP); if the serum and urine M protein were unmeasurable then a \>90% decrease in the difference between involved and uninvolved FLC levels.

Time frame: Response was assessed every two cycles on treatment. Treatment duration in months was a median (range) of 5.1 (0.8-6.1).

Population: The analysis population is comprised of eligible and treated participants.