Mozobil Clinical Efficacy in Multiple Myeloma

The efficacy and safety of Mozobil in conjunction with granulocyte-colony stimulating factor (G-CSF) in multiple myeloma (MM) patients were evaluated in a randomized, double-blind, placebo-controlled, multicenter phase 3 study (study 2).

Mozobil + G-CSF increased the number of patients achieving both minimum and target CD34+ cells/kg in fewer apheresis sessions compared with placebo + G-CSF.

Study 2 Endpoints

• Primary endpoint:

• Number of patients reaching a target of ≥ 6 × 10⁶ CD34+ cells/kg in ≤ 2 days of apheresis

• Secondary endpoints:

• Number of patients who achieved a target of > 6 x 10⁶ CD34+ cells/kg in < 4 days of apheresis
• Number of patients who achieved a minimum of ≥ 2 × 10⁶ CD34+ cells/kg in <4 days of apheresis or less
• Number of apheresis days required to reach the target of ≥ 6 × 10⁶ CD34+ cells/kg
• Time to neutrophil and platelet engraftment
• Graft durability at 100 days, 6 months, and 12 months
• Safety of Mozobil (0.24 mg/kg) + G-CSF

Patients

Study 2 enrolled 302 patients with MM, 148 to Mozobil + G-CSF and 154 to placebo + G-CSF. Mean age was 58.2 years for Mozobil patients and 58.4 years for placebo patients. As with study 1 most patients were Caucasian (81.1%). Unlike study 1, a similar percentage of patients in both arms had advanced disease (stage III), but more Mozobil patients had stage I MM (19%) compared to G-CSF + placebo patients (12%). This difference is not expected to influence efficacy.

Seven of 154 patients (4.5%) treated with placebo + G-CSF who failed to collect either 0.8 x 10⁶ cells/kg after 2 days of apheresis or at least 2 x 10⁶ CD34+ cells/kg in 4 apheresis days, or MM patients who planned for tandem transplant and did not collect at least 4 x 10⁶ CD34+ cells/kg in 4 or fewer apheresis days, entered the rescue protocol and went on to receive open label Mozobil + G-CSF. No patients on the Mozobil arm entered the rescue protocol. All rescue patients collected ≥ 2x 10⁶ CD34+ cells/kg, and 42.9% of patients collected more than 6 x 10⁶ CD34+ cells/kg. All rescue patients proceeded to transplantation, and 4 had tandem transplants.

Study 2 Outcomes

• More than twice as many patients achieved the primary endpoint of ≥ 6 x 10⁶ CD34+ cells/kg within 2 apheresis days with Mozobil + G-CSF than with placebo + G-CSF.
• 72% of MM patients who were mobilized with Mozobil + G-CSF collected ≥ 6 x 10⁶ CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions, compared with 34% of patients who were mobilized with placebo + G-CSF (p < 0.001).

Genzyme. Data on file.

Kaplan-Meier Estimate of Percentage of MM Patients Who Achieved ≥ 6 x 10⁶ CD34+ cells/kg by Apheresis Day

• The median number of days to reach target number of CD34+ cells/kg was 1 day with Mozobil + G-CSF vs. 4 days with placebo + G-CSF .