ALEMTUZUMAB DOSING BY RECIPIENT WEIGHT IS IMPORTANT FOR REDUCED-INTENSITY CONDITIONING FOR ALLOGENEIC TRANSPLANTATION.

Abstract

From June 2002, to August 2006, our institution used reduced-intensity conditioning (RIC) regimens for allogeneic transplantation of 40 adult at-risk older patients or patients with comorbid conditions. Malignancies included multiple myeloma, AML, CML, NHL, MDS, CLL, and one renal cell carcinoma. Thirteen (32%) were in CR at time of transplant, whereas 27 (68%) had relapsed or refractory disease. Median age was 50 years (range 24-66) and median follow-up was 8 months (1-36 months). Degree of HLA match at A, B, and DR was 6/6 or better for 31 patients and either single antigen or allele mismatches for the others. Three RIC regimens consisted of intravenous infusions of: fludarabine 30 mg/m2 × 5 days and melphalan 140 mg/m2 × 1 day in all groups, and of Alemtuzumab 20 mg/d × 5 days (protocol 1), × 3 days (protocol 2), and × 2 days (protocol 3). Twenty-three patients received MUD products and 17 received MRD products; cell source was bone marrow (17), PBSC (19), cord blood (1), and combination products (3). All patients received an adequate CD34+ cell dose or TNC dose (cord blood transplant). GVHD prophylaxis was tacrolimus tapering after day +100 and mycophenolate mofetil tapering after day +30. Determination of the optimal dose of alemtuzumab was a goal of this study. All patients except one achieved a WBC graft. Relapse or disease progression occurred in only 37% of protocol 3, 40% of protocol 2, and 67% of protocol 1. Although alemtuzumab doses were given in a standard fashion not adjusted for body weight or surface area, it was found that a lack of consideration of patient size did not represent the intent of the given protocols. Weight-based alemtuzumab dose adjustment showed that a much broader dose range than expected had occurred. Those receiving protocol 1 were in a dose range of 1.01 to 1.90 mg/kg; for protocol 2, the range was 0.36 to 1.08 mg/kg; for protocol 3, the range was 0.36 to 0.70. The median dose of alemtuzumab for the cohort was 0.68 mg/kg. A clustering of acute GVHD grades I to II appeared below the median dose at approximately 0.55 mg/kg; only one patient had grade IV GVHD. In summary, these data indicate that using the patient9s body weight in the determination of an optimal alemtuzumab dose is a more reasonable approach to developing and standardizing RIC protocols with this drug.