Abstract
The clinical benefit of autologous hematopoietic stem cell transplant (ASCT) for multiple myeloma (MM) partly depends on the ability to collect sufficient hematopoietic stem cells (HSCs) from peripheral blood (PB). Risk factors for impaired HSC mobilization are increasingly common in patients with MM undergoing ASCT in the current treatment landscape, including advanced age, presence of cytopenias and prior exposure to radiation, lenalidomide and/or anti-CD38 monoclonal antibodies (mAb). Motixafortide is a novel high affinity CXCR4 antagonist indicated, in combination with G-CSF, for mobilization of HSCs to the PB for collection and subsequent ASCT in MM. In the GENESIS trial (NCT03246529), a single dose of motixafortide, in combination with G-CSF, enabled a significantly greater proportion of subjects to mobilize ≥6 × 106 CD34+ cells/kg in up to 2 aphereses. Here we report the results of subgroup analyses of the GENESIS trial evaluating baseline characteristics and risk factors for impaired mobilization.
The GENESIS trial was a multicenter, randomized, double-blind, placebo-controlled Phase 3 study. The primary endpoint was % of subjects mobilizing ≥6 × 106 CD34+ cells/kg after a single dose of motixafortide in up to 2 aphereses. CD34+ cell enumeration was assessed by both central and local laboratories. Central lab results enabled standardization across sites, while local lab results were used for clinical decisions; such as determining if a subject reached the collection goal. Pre-planned subgroups included gender, age, response status at randomization, and baseline platelets. A post-hoc subgroup analysis based on prior radiation, lenalidomide and/or anti-CD38 mAb prior to mobilization was performed.
A total of 122 patients were enrolled. Demographics were comparable between arms, including for risk factors of impaired mobilization (Table 1). Overall, 70.0% (central lab) and 92.5 % (local lab) of subjects in the motixafortide arm met the primary endpoint vs 14.3% (central lab) and 26.2 % (local lab) with G-CSF alone. Sub-analysis of the efficacy of motixafortide in subgroups at increased risk of impaired mobilization demonstrated consistently higher collection rates compared to G-CSF alone (Table 2) including: age >65 years (motixafortide+ G-CSF: 70.4%, G-CSF alone: 16.7%), prior RT (motixafortide+ G-CSF: 55.6%, G-CSF alone: 0%), and prior lenalidomide (motixafortide+ G-CSF: 73.7%, G-CSF alone: 10.7%) . Figure 1 shows the Cochran-Mantel-Haenszel common proportions difference of the different sub-groups.
Taken together, these data demonstrate a consistent benefit of motixafortide + G-CSF over G-CSF mobilization for all patients, including those at risk for impaired HSPC mobilization.