Dr. Andreas Tanzmann (Wien/ AT), Manuela Branka (Wien/ AT), Vera Kolovratova (Wien/ AT), Michaela Horvath (Wien/ AT), Martin Kurz (Wien/ AT), Patricija Raijsp (Wien/ AT), Markus Dettke (Wien/ AT), Elke Zipperer (Wien/ AT), Rene Geyregger (Wien/ AT), Konrad Rosskopf (Graz/ AT), Hildegard Greinix (Graz/ AT), Prof. Dr. Nina Worel (Wien/ AT)
Background
This study evaluates the safety and efficacy of plerixafor (PLER), a CXCR4 antagonist, in mobilizing hematopoietic progenitor cells for autologous hematopoietic cell transplantation (HCT) in multiple myeloma (MM) patients.
Methods
This is a phase IV, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with MM scheduled for 2 autologous HCTs mobilized with granulocyte colony-stimulating factor (G-CSF; 2x5 µg/kg) s.c. daily for up to 5 days were eligible. On day 4 of G-CSF, peripheral blood (PB) CD34+ count was analyzed and patients were enrolled if they had 15-40 CD34+ cells/µL. They received either PLER at a dose of 240 µg/kg or placebo 4-12 hours before start of apheresis. The primary endpoint was to collect 6 x106 CD34+ cells/kg in one apheresis, thus enabling 2 autologous HCTs. In addition, CD34+ and lymphocyte subsets, colony forming units (CFU) and engraftment kinetics were analyzed.
Results
The study was designed for 90 patients but was stopped after 21 patients due to approval of daratumumab also for first line therapy in MM, which led to insufficient mobilization (i.e. <15 CD34+ cells/µl in the PB) in the predefined patient cohort. With PLER pre-apheresis CD34+ cell counts were significantly higher than with placebo (median 93,3/µL vs. 29,34; p-Value 1.71E-08). Ten of 21 (48%) patients received PLER and 11 (52%) placebo. All patients in the PLER group met the primary endpoint with a median of 7.6 x106 (range 7.03 to 13.18) CD34+ cells/kg compared to none in the placebo group (median 2.52 x106 CD34+ cells/kg, range 1.40 to 5.27 x106 CD34+ cells/kg). PLER was tolerated well with only rare cases of gastrointestinal disorders.
Conclusion
In contrast to G-CSF alone, PLER + G-CSF allowed to collect >6x106 CD34+ cells/kg for 2 autologous HCTs in only one apheresis session in moderately mobilizing MM patients (i.e. 15-40 CD34+ cells/µl). This not only reduces apheresis procedures and workload for operators and technicians but also facilitates planning of apheresis and increases patient"s comfort.
Therefore, PLER should be considered not only in cases of imminent mobilization failure but also in patients with moderate mobilization.
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