Results of Allogeneic Transplantation As First Line Rescue Therapy in Patients with Multiple Myeloma Relapsing to a Prior Autograft: Role of Conditioning Regimen

INTRODUCTION: The availability of new and effective drugs in multiple myeloma has modified the standard management of these patients. Accordingly, allogeneic stem cell transplantation (alloSCT) is not routinely used upfront except in very specific subgroups of high risk patients. In spite of this data, the number of alloSCT has increased along the last years, most patients undergoing alloSCT beyond first relapse.

AIM: In the current study we analyze the outcome of alloSCT as second line therapy among patients who have relapsed to a first line which included autologous stem cell transplantation (autoSCT) and we have compared their outcomes depending on the type of conditioning.

PATIENTS AND METHODS: We selected 573 patients transplanted from 1991 to 2014 included in the EBMT data registry who received alloSCT within the first year after having relapsed to first line treatment including autoSCT. One hundred and two patients received myeloablative conditioning (MAC), 284 reduced intensity conditioning (RIC), 120 non-myeloablative (NMA) and 67 underwent tandem auto-alloSCT (Auto-allo). Patients characteristics are summarized in table 1.

RESULTS: With a median follow-up of 47 months, median overall survival (OS) was 22.2 months with 39.6% and 31% patients surviving at 3 and 5 years, respectively. Variables which significantly influenced on OS in multivariable analysis were: type of conditioning [HR for MAC 1.68, (95% CI =1.16-2.44), p=0.006] , age [HR 1.02, (95% CI =1.01-1.04), p=0.001], disease status at transplant [HR for less than PR 1.56, (95% CI =1.07-2.28), p=0.01] and time from first relapse to SCT [HR 0.95, (95% CI =0.91-0.99), p=0.02 ]. Time from first autoSCT to relapse influenced on OS in univariate but not in multivariable analysis. Median Progression free survival (PFS) was 8.1 months with 17% and 12% patients being free of progression at 3 and 5 years after alloSCT. Variables which significantly influenced on PFS in multivariable analysis were: type of GVHD prophylaxis [HR for use of alemtuzumab 1.46, (95% CI =1.03-2.07), p=0.03], disease status at transplant [HR for less than PR 1.67, (95% CI =1.19-2.33), p=0.002 ], time from first autoSCT to relapse [HR 0.99, (95% CI =0.98-0.99), p=0.03 ] and time from first relapse to SCT [HR 0.95, (95% CI =0.92-0.98), p=0.009].

For patients younger than 53 years old, who underwent RIC or NMA alloSCT> 9 months after relapse with GVHD prophylaxis other than alemtuzumab median OS and PFS were 80 and 17 months, respectively.

CONCLUSSION: Allogeneic stem cell transplantation allows to obtain remarkable median OS and PFS when used as rescue therapy after a relapse to first line treatment which includes autoSCT. Use of approached other than MAC within the conditioning and alemtuzumab as GVHD prophylaxis allows to obtain the better outcomes.

Table 1: