Additional plerixafor to granulocyte colony‐stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma

Tim Hartmann, Kai Hübel, Ina Monsef, Andreas Engert, Nicole Skoetz

Autologous stem cell transplantation is widely used to restore functioning bone marrow in people with malignant lymphoma or multiple myeloma after myeloablative chemotherapy. Results of some clinical trials indicate that plerixafor in addition to granulocyte colony-stimulating factors (G-CSF) compared to G-CSF only could lead to an increased mobilisation and release of CD34-positive cells, facilitating effective apheresis. To evaluate the efficacy and safety of additional plerixafor to G-CSF for haematopoietic stem cell mobilisation in people with malignant lymphoma or multiple myeloma. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1990 to September 2015), as well as conference proceedings (American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; American Society for Blood and Marrow Transplantation; European Group for Blood and Marrow Transplantation) for studies. Two review authors independently screened search results. We included randomised controlled trials (RCTs) comparing plerixafor in addition to G-CSF compared to G-CSF only for stem cell mobilisation in people with malignant lymphoma or multiple myeloma of all stages and ages. We included full text as well as abstracts and unpublished data if sufficient information on study design, participant characteristics, interventions, and outcomes was available. We excluded cross-over trials, quasi-randomised trials, and post-hoc retrospective trials. Two review authors independently screened the results of the search strategies, extracted data, assessed quality, and analysed data according to standard Cochrane methods. We performed final interpretation with an experienced clinician. 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.