Poster Session I: Myeloma and other monoclonal gammopathies - Clinical
The role of allogeneic hematopoietic stem cell transplantation (AHCST) remains controversial in myeloma, with myeloablative regimens associated with an unacceptable transplant-related mortality (TRM). Despite this, even in an era of increasing drug treatments, AHCST remains one of the only curative options. Previous studies have included a mixture of different conditioning regimens in a variety of patients. Here we report our results using a non-myeloablative (NMA) approach in a selected higher-risk myeloma patient population at our institution.
We report the outcomes of 37 patients with myeloma, transplanted using an NMA Fludarabine/Cyclophosphamide (FC) conditioning regimen without T cell depletion.
We reviewed all patients receiving AHSCT at our centre between November 2000 and October 2017 All patients received fludarabine 25 mg/m2/day for 5 days and cyclophosphamide 1 g/m2/day for 2 days. Short course methotrexate and ciclosporin were used for GVHD prophylaxis without T-cell depletion. Standard supportive care was employed.
37 myeloma patients (median age 52 years, range 31-63) underwent AHCST with 28 (76%) IgG, 5 (14%) IgA, 3 (8%) LC-only and 1 (3%) non-secretory disease. For those with recorded ISS (33), 8 (24%) were ISS1, 12 (36%) ISS2 and 13 (39%) ISS3. For those with recorded cytogenetics (19), high risk features (defined as t(4;14), t(14;16), t(14;20), 17p- or 1q+) were present in 14 cases (74%).
At the time of transplant, patients had received a median of 2 prior lines of therapy (range 1-5), with 19 (51%) in 1st remission, 16 (43%) in 2nd, and 2 (5%) in 3rd. Status at the time of transplant was as follows: CR 27 (73%), VGPR 1 (4%), PR 2 (5%), SD 3 (8%), PD 4 (11%). 34 (92%) had a received previous autograft. All patients received peripheral blood stem cells from either HLA-matched sibling (59%) or unrelated (41%) donors.
TRM was very low (3% at 1 year and 9% at 5 years) precluding analysis of specific risk factors. Incidence of acute GvHD (including late onset acute GvHD with cessation of ciclosporin up to day 180) was 38% (Grade 1-4) and 14% (Grade 3-4). The incidence of chronic GvHD was 55%.
Incidence of progression was 26% at 1 year and 49% at 5 years, and was significantly higher in patients who had received >1 prior line of therapy (p = 0.05, Log Rank test) and those in less than a VGPR at the time of transplant (p = 0.05). Patients who developed aGvHD had a significantly lower incidence of relapse (p = 0.05) consistent with a graft-versus-myeloma effect.
Progression-free and overall survival were 74% and 91% at 1 year, and 57% and 66% at 5 yearsrespectively, with worse outcome in those who received >1 prior line of treatment (p = 0.04) and in those without aGvHD (p = 0.03).
NMA T-replete AHSCT using a low dose Fludarabine/Cyclophosphamide platform is a safe approach with very low TRM. In this group of carefully selected younger patients with predominantly high-risk myeloma, PFS was achieved in > 50% of patients at 5 years which is likely to represent a cure. Less heavily pre-treated patients in a deeper response had better outcomes, with GVHD associated with freedom from relapse, providing evidence for a graft-versus-myeloma effect. This approach should be considered as a treatment option in young, high-risk patients.