PF642 REDUCED INTENSITY ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IS A SAFE AND EFFECTIVE TREATMENT OPTION IN HIGH RISK MYELOMA PATIENTS – A SINGLE CENTRE EXPERIENCE
Authors: Jurgensen‐Rauch A. , Gibbs S. , Farrell M. , Cavenagh J. , Eccersley L. , Gribben J. , Hallam S. , Oakervee H. , Davies J. , Sive J. 
Published: June 2019

Background:

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.

Aims:

We report the outcomes of 37 patients with myeloma, transplanted using an NMA Fludarabine/Cyclophosphamide (FC) conditioning regimen without T cell depletion.

Methods:

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.

Results:

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).

Summary/Conclusion:

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.

image