Abstract: We identified four RCTs fitting the inclusion criteria. However, two of these closed prematurely due to low recruitment and did not report results. The remaining two trials evaluated 600 participants with multiple myeloma or non-Hodgkin lymphoma. In both studies the experimental group received G-CSF plus plerixafor and the control group received G-CSF plus placebo. The meta-analysis showed no evidence for differences between plerixafor and placebo group regarding mortality at 12 months (600 participants; risk ratio (RR) 1.00, 95% confidence interval (CI) 0.59 to 1.69; P = 1.00; moderate-quality evidence) and adverse events during stem cell mobilisation and collection (593 participants; RR 1.02, 95% CI 0.99 to 1.06; P = 0.19; high-quality evidence). Regarding the outcome successful stem cell collection, the meta-analysis showed an advantage for those participants randomised to the plerixafor group (600 participants; RR 2.42, 95% CI 1.98 to 2.96; P < 0.00001; high-quality evidence). As there was high heterogeneity between studies for the number of transplanted participants, we did not meta-analyse these data. In the multiple myeloma study, 95.9% (142 participants) in the plerixafor arm and 88.3% (136 participants) in the placebo arm underwent transplantation (RR 1.09, 95% CI 1.02 to 1.16); in the non-Hodgkin lymphoma trial, 90% (135 participants) in the plerixafor group versus 55.4% (82 participants) in the placebo group could be transplanted (RR 1.62, 95% CI 1.39 to 1.89). In both trials there was no evidence for a difference between participants in the plerixafor and placebo group in terms of time to neutrophil and platelet engraftment in transplanted participants. None of the trials reported on the outcomes quality of life and progression-free survival. The results of the analysed data suggest that additional plerixafor leads to increased stem cell collection in a shorter time. There was insufficient evidence to determine whether additional plerixafor affects survival or adverse events. The two trials included in the meta-analysis, both of which were conducted by the Genzyme Corporation, the manufacturer of plerixafor, were published several times. Two more RCTs examining the addition of plerixafor to a G-CSF mobilisation regimen terminated early without publishing any outcome. The trials included nine and five participants, respectively. Another RCT with 100 participants was recently completed, but has not yet published outcomes. Due to the unpublished RCTs, it is possible that our review is affected by publication bias, even though two trials failed to recruit a sufficient number of participants to analyse any data.

Plain-language summary: We searched several medical databases and identified four randomised controlled trials that met our inclusion criteria. Two of the four studies terminated early due to low recruitment (14 participants included) and did not release any results. We were therefore unable to include them in our statistical analysis. The two published analysed trials included 600 participants with multiple myeloma and non-Hodgkin lymphoma. In both studies, the experimental group received G-CSF plus plerixafor subcutaneously, and the control group received G-CSF plus placebo. Both trials were sponsored by Genzyme, the manufacturer of plerixafor. We were able to conduct a meta-analysis of the data of the two studies for the outcomes mortality at 12 months, successful stem cell collection, and adverse events. We found no evidence for a difference between the plerixafor and placebo group for the outcomes mortality at 12 months and adverse events during stem cell mobilisation period. The meta-analysis showed an advantage for those participants randomised to plerixafor for the outcome successful stem cell collection. Furthermore, in both studies the time to collect a defined number of stem cells was significantly shorter in the plerixafor group compared to the placebo group. In the study that enrolled people with multiple myeloma, 95.9% of the participants in the plerixafor arm and 88.3% in the placebo arm underwent transplantation. In the study that examined people with non-Hodgkin lymphoma, 90% of the participants in the plerixafor group and only 55.4% in the placebo group could be transplanted. It seems that especially people with non-Hodgkin lymphoma benefit from the addition of plerixafor in terms of successful transplantation, but there was no evidence for a difference for time to neutrophil and platelet engraftment in transplanted participants. None of the trials reported on quality of life or progression-free survival. The quality of the evidence was high for adverse events and successful stem cell collection and moderate for mortality at 12 months. The main limitation was a wide confidence interval.