AMD3100 Plus G-CSF Use in Proven Poor Mobilizers in a Compassionate Use Protocol (CUP).

Abstract

AMD3100 (A), an inhibitor of SDF-1∞ binding to CXCR4, has been used alone and with G-CSF (G) to mobilize CD34+ cells from healthy volunteers and donors and from cancer patients undergoing autologous transplantation. In several studies it enhanced mobilization of poor mobilizers. Therefore, a CUP was submitted to the FDA; more than 100 patients (most commonly NHL; N=42) have been entered. Results from the first 70 patients enrolled are reported here. Three patients underwent a second mobilization with A following initial failure (2) and disease relapse (1); data on the first mobilization is in this report. Entry requirements include documented inability to mobilize 2 x 106 CD34+ cells/kg. Patients must have acceptable cardiac and pulmonary status, no active infection, and to have WBC >3.0 x 109/L, ANC > 1.5 x109/L, PLT >100,000 x 109/L, LFT within 2 x ULN, and creatinine clearance >60 ml/min. as well as other acceptable laboratory values. After signing consent and undergoing history, physical, laboratory, CXR, and ECG evaluation, patients are given G (10 mg/kg) for 4 days. At about 10 p.m. on day 4 they receive 240 mg/kg of A subcutaneously. The next a.m. they receive G and undergo apheresis. The evening A, the a.m. G, and the apheresis are repeated until enough cells are collected or until it is clear insufficient cells could be collected. There were 38 males and 32 females. Five were 18 years or younger (10, 12, 13, 16 and 18 years). The rest ranged in age from 21 to 81 years. Most common diseases were NHL (31), MM (14), AML (8), and Hodgkin’s disease (HD) (10). The 70 patients had undergone 93 possible mobilizations and 16 patients failed multiple prior regimens. Nearly all (91/93) prior mobilization regimens contained G. The most common regimens were G alone (33), cyclophosphamide plus G (17), and cyclophosphamide plus G plus other agents (30). In a subset of patients (N=27) the median time between the prior failed mobilization and the CUP mobilization was 34 days. A was generally well tolerated with AEs being similar to that previously reported. Only one SAE was felt related - patient with worsening of GI symptoms. The percent of patients collecting >2 x 106 cells/kg for the more common cancers were 58 for NHL, 64 for MM, 50 for AML, and 70 for HD. For those collecting >2 x 106 cells/kg (N=40) the median collection was 4.72 106 cells/kg in a median of 3.5 aphereses. The number of these patients transplanted was 36 of 40 with 31 successful engraftments, 3 pending, and two deaths post successful PMN, but not PLT engraftment. Of all the patients transplanted 4 additional patients have died. Durability has been good with at least 24 patients at 6 months or beyond. The success of mobilization compares very favorably with prior published data. A offers a generally safe and effective way to enhance mobilization of patients who have previously failed mobilizations.