The association of mobilising regimen on immune reconstitution and survival in myeloma patients treated with bortezomib, cyclophosphamide and dexamethasone induction followed by a melphalan autograft

Abstract

G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF\u2009+\u2009CY. Patients failing G-CSF only mobilisation were excluded. 601 patients were included: 328: G-CSF\u2009+\u2009CY, 273: G-CSF only. Mobilisation arms were comparable in terms of age, Revised International Staging System (R-ISS) groups and post-transplant maintenance therapy. G-CSF\u2009+\u2009CY mobilisation generated higher median CD34\u2009+\u2009yields (8.6 vs. 5.5\u2009×\u2009106/kg, p\u2009<\u20090.001). G-CSF only mobilisation was associated with a significantly higher lymphocyte count at day 15 post-infusion (p\u2009<\u20090.001). G-CSF only mobilisation was associated with significantly improved OS (aHR\u2009=\u20090.60, 95%CI 0.39–0.92, p\u2009=\u20090.018) and TTNT (aHR\u2009=\u20090.77, 95%CI 0.60–0.97, p\u2009=\u20090.027), when adjusting for R-ISS, disease-response pre-transplant, age and post-transplant maintenance therapy. This survival benefit may reflect selection bias in excluding patients with unsuccessful G-CSF only mobilisation or may be due to enhanced autograft immune cell content and improved early immune reconstitution.