Has Allogeneic Transplantation a Role in the Management of Plasma Cell Leukaemia? A Study on Behalf of the Myeloma Subcomittee of the Chronic Leukaemia Working Party of the EBMT

Abstract 2008

We have previously reported a dismal outcome for patients with Plasma Cell Leukaemia (PCL) undergoing autologous transplantation, although such patients represent the younger and fittest with this condition and show superior survival to reports of non transplant patients. In this study we report two analyses of 85 eligible patients with PCL who received an allogeneic transplantation (Allo) between 1984 and 2009 and 411 patients receiving autologous transplantation (Auto) in the same period and a further comparison with 850 (Allo) myeloma MM.The first analysis was restricted to the years 1998 to 2009 allowing the identification of a large Myeloablative (MAC) population (n=45) and a smaller reduced intensity (n=17) conditioning (RIC) group. On account of the number of comparisons in the study and the size of the sub populations, only statistically highly significant differences are reported; less significantly powerful differences are viewed as a trend. Patients treated with MAC and RIC were essentially similar although significantly younger (45.9 and 52.9 yrs respectively) than the Auto patients (55.9 yrs) at the time of diagnosis, with similar differences at the time of transplant. RIC patients had a longer time (10.2 months) to transplant than the MAC (6.0m) and Auto (5.8m) groups. No difference was seen in rates of engraftment, acute or chronic graft versus host disease. MAC patients had a higher Complete Response (CR) than Auto. Progression Free Survival (PFS) at 12 and 60 months respectively (with Confidence Intervals) was as follows: Auto; 0.51 (0.45 – 0.57) and 0.10 (0.06 – 0.15), MAC; 0.39 (0.26 – 0.57) and 0.19 (0.09 – 0.39), RIC; 0.43 (0.23 – 0.80) and 0.11 (0.02 – 0.67) with the MAC and RIC curves possibly crossing the Auto curve between 2 and 4 years. These differences are due to highly significant differences in Non Relapse Mortality (Auto better) and Progression (Auto worse) This translates into Overall Survival (OS) at similar times (12 and 60 months) to PFS as follows: Auto; 0.73 (0.68 – 0.78) and 0.25 (0.19 – 0.33), MAC; 0.46 (0.33 – 0.65) and 0.27 (0.16 – 0.47), RIC; 0.59 (0.38 – 0.91) and 0.19 (0.04 – 0.93). The differences between MAC and RIC were not statistically significant. It was noted that whereas Auto patients continue to relapse with time there is a (small) plateau of survivors in both MAC and RIC. These findings are confirmed in the larger non selected analysis of all Auto and Allo patients Although age is seen as a strong prognostic factor favouring the Allo patients appropriate adjustment was made in the analysis. In the comparison of Allo in PCL v. MM the PFS and OS for PCL was inferior to MM: Data at 48 months for PFS and OS respectively: MM 0.22 (0.19 – 0.26) and 0.44 (0.40 – 0.48), PCL 0.20 (0.10 – 0.41) and 0.32 (0.19 – 0.53). In all three analyses the PCL Allo group shows a clear plateau at about 0.2 (20%) similar that seen in a number of recent studies of Allo transplantation in MM, but at a lower level. This contrasts with the ongoing attrition of patients experiencing progression in Auto transplantation.

This study presents the first major analysis of Allo transplantation in PCL, confirms the poor prognosis with all types of transplant therapy while indicating it remains the best option for patients with PCL. Further improvements in the management of NRM can improve the outcome for these patients.