Efficacy of Novel Agents on Soft-Tissue Plasmacytomas in Patients with Relapsed Multiple Myeloma

Introduction: the frequency of soft-tissue plasmacytomas (EMPs) is high in patients with relapsed multiple myeloma (MM). There are two types of plasmacytomas: 1) paraskeletal: originating from focal bone involvement (vertebrae, ribs, sternum, skull) and 2) extramedullary: originating from hematogenous spread (skin, liver, CNS). The reported incidence in relapsed patients is 3-34% for paraskeletal and 3-10% for extramedullary plasmacytomas. The presence of soft-tissue masses is associated with poor prognosis and the efficacy of novel agents is not well established. There are some reports about the lack of efficacy of thalidomide (Bladé et al, Br J Haematol 2001; 113: 422-24) while some efficacy has been reported with bortezomib (Rosiñol et al, Eur J Haematol 2006;76:405-08) and pomalidomide (Detweiler et al, Leukemia 2011, 25; 906-908).

Aim: to analyze the effectiveness of novel drugs (thalidomide, bortezomib, lenalidomide, pomalidomide, carfilzomib) in patients with relapsed MM and EMPs.

Patients and Methods: patients with EMPs (paraskeletal or extramedullary) at the time of first or subsequent relapses from our database from Hospital Clínic of Barcelona who were treated with novel agents were analyzed. Only patients receiving the novel drugs in monotherapy or in combination with corticosteroids were included in the analysis. Patients receiving combination therapy including two novel drugs (i.e. VTD, VRD) were excluded.

Results: 29 patients (median age 61, M 17/F 12) with relapsed myeloma and EMPs were treated with bortezomib. The median number of previous therapies was one. 22 patients had paraskeletal and 7 extramedullary plasmacytomas. The median number of cycles received was 4. The serological response rate was: 4% CR, 27% PR, 7% MR, 24% SD, 17% PD, 7% early death, 14% non evaluable. The response of the plasmacytomas were: 14% CR, 17% PR, 10% SD, 41% PD, 4% early death, 14% non evaluable. The median PFS from the initiation of bortezomib was 3.9 months. Sixteen patients (median age 49 years, M 6/F 10) were treated with lenalidomide. 13 patients had paraskeletal and 3 extramedullary plasmacytomas. The median number of previous therapies was two. The median number of cycles was 5.5. Serological response was: 38% PR, 12% MR, 19% SD, 19% PD, 12% non evaluable. The plasmacytoma response was: 25% PR, 19% SD, 44% PD, 12% non evaluable. The median PFS from initiantion of lenalidomide was 8.4 months. Nine patients (median age 61 years, 3M/6F) were treated with pomalidomide at relapse. The median number of previous therapies was 4. Two patients had paraskeletal and 7 extramedullary plasmacytomas. The median number of cycles was 2. Serological response rate was: 44% PR, 11% SD, 23% PD, 11% non evaluable. However, none of the patients showed response of the plasmacytomas (11% SD, 77% PD, 11% early death). The median PFS was 1.3 months. 8 patients (median age 49 years, 6M/2F) were treated with thalidomide at relapse. The median number of previous therapies was one. Six patients had paraskeletal and 2 extramedullary plasmacytomas. The median number of cycles of thalidomide received was one. None of the patients showed serological response (25% stable disease (SD), 50% progressive disease (PD), 25% early death) or reduction in the size of the plasmacytomas (50% SD, 50% PD). The median progressive free survival (PFS) from initiation of treatment with thalidomide was 1.6 months.

Four patients (median age 62, 2M, 2F) were treated with carfilzomib. The median number of previous therapies was 3. The EMPs type was paraskeletal (1) and extramedullary (3). The median number of cycles administered was one. None patient responded to carfilzomib: serological response rate: 75% SD, 25% PD; plasmacytomas response: 100% PD. The median PFS was 0.7 months. The median survival in the overall series of patients with soft tissues masses at relapse treated with novel agents was 15.2 months.

Conclusions: The efficacy of novel drugs in the treatment of EMPs is limited, being the most effective bortezomib and lenalidomide. None of the patients treated with thalidomide, pomalidomide or carfilzomib showed any response of the soft-tissue involvement (paraskeletal or extramedullary). Finally, the presence of plasmacytomas at relapse is associated with poor OS even in the era of novel agents. However, the efficacy of these novel agents as part of front-line therapy is unknown.