Weight Based Plerixafor Dosing Reduces Side Effects in Stem Cell Mobilization

WEIGHT BASED PLERIXAFOR DOSING REDUCES SIDE-EFFECTS IN STEM CELL MOBILIZATION

 

Topic Significance & Study Purpose/Background/Rationale

Autologous stem cell mobilization is enhanced by use of plerixafor in combination with G-CSF, particularly in otherwise poor mobilizers.  At New York Presbyterian Weill/Cornell we determined CD34 count on day four of G-CSF and added plerixafor for those whose CD34 count was <20 cells/mcL. Plerixafor dosing was based on both weight and kidney function (EGFR >60 ml/min/m2: 24 mg; EGFR<60 and weight >50 Kg: 24 mg; EGFR <60 and weight < 50 Kg: 12 mg).  This algorithm was implemented in early 2013 and was quite effective in stem cell mobilization. The required number of apheresis per patient was much reduced (Cushing et al, submitted). However, out of 55 patients, 12 experienced a variety of side effects including diarrhea, abdominal pain, nausea, vomiting, sweating, insomnia, paresthesias, jaw tightness, blurred vision, difficulty walking, and in one case hallucinations.  These side-effects occurred within hours of administration of plerixafor and in most patients resolved within 24 hours.

Methods, Intervention, & Analysis

 There was a clear association between body weight and occurrence of this syndrome. The median weight of those with side-effects was 60, compared to a median weight of 80 for those without side-effects.(p<0.001 -figure). The dosing algorithm was adjusted as follows: EGFR>60 and weight of >75 Kg: 24 mg, 51-75 Kg: 18 mg and </= 50 Kg :12 mg. Further dose reductions are implemented for pts with reduced EGFR. EGFR is <50 and >75 kg: 16 mg, 51-75 Kg: 12 mg, and</= 50 Kg: 8 mg. 

 

Findings & Interpretation

Since adoption of this new algorithm only 3 of 45 patients have experienced side-effects (P=0.04).   One patient had severe nausea, one had severe diarrhea and one experienced paresthesias.

 

 

Discussion & Implications

The new dosing algorithm has not had a negative impact on stem cell mobilization.  Standard doses of plerixafor can cause severe gastro-intestinal disturbance in patients with low body weight. Adjustment for body weight can prevent most of these side-effects.