PB2158 POMALIDOMIDE, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (PCD) IS AN EFFECTIVE SALVAGE REGIMEN FOR MULTIPLE MYELOMA (MM) PATIENTS RELAPSED ON OR REFRACTORY TO DARATUMUMAB
Authors: Brioli A. , Ernst T. , Hilgendorf I. , Heidel F. , Hunstig F. , Hochhaus A. , von Lilienfeld‐Toal M. 
Published: June 2019

Background:

Daratumumab (dara) has recently been approved as monotherapy or in combination with lenalidomide (daraRd) or bortezomib (daraVd) for the treatment of relapsed and/or refractory MM patients (pts). However, treatment options for pts progressing after dara are limited, and little data are available on the efficacy of more conventional therapy regimens used as salvage treatment after progression during treatment with dara.

Aims:

To evaluate the efficacy and safety of pomalidomide/cyclophosphamide/dexamethasone (PCD) as salvage therapy after progression during dara treatment.

Methods

Medical records of pts treated at Jena University Hospital were reviewed to identify pts treated with PCD as salvage treatment after failing dara therapy. Ten patients were identified. Of these 9 received at least 1 cycle of PCD therapy and were included in the present preliminary analysis. Statistical analysis included descriptive statistics and survival analysis. Progression free survival (PFS) and overall survival (OS) were calculated from the time of start of PCD treatment. Data cut off for the present analysis was 1st of February 2019. Statistical analysis was performed with SPSS version 20.0.

Results:

Median age at the start of PCD was 62 years (range 51‐75), with 2 IgG, 2 light chain, 3 IgA, 1 IgM and 1IgD MM, respectively. Three pts had extramedullary (EM) disease. PCD was given after a median of 4 previous lines of therapy (range 2‐8). All pts except one had previously been treated with melphalan, 7 had received autologous stem cell transplantation (SCT) and one pt had received an allogeneic SCT. All patients had received an IMiD in the course of their history (7 pts lenalidomide, 1 pt thalidomide and 1 pt both agents), with 8/9 pts progressing during IMiD therapy. Eight pts had been treated with bortezomib and 4/8 had received carfilzomib; 7/8 pts were refractory to proteasome inhibitors. In all pts but one treatment with PCD followed immediately dara treatment. Before treatment with PCD, 5 pts had been treated with Dara monotherapy, 3 pts had received daraRd and 1 pt daraVd. Responses to dara had been limited: 3 partial responses (PR) but 6 pts with primary refractory disease (including 2 pts with EM disease). Median number of cycles of dara was 2.5 (range 1‐8). Regarding PCD, the median daily dose of pomalidomide was 3 mg (range 1‐4 mg), median cumulative doses of cyclophosphamide and dexa for each cycle were 900 mg/m2 (range 0‐1800 mg/m2) and 160 mg (range 0‐320 mg), respectively. The median number of cycles of PCD was 5 (range 1‐26); 3 patients are still on treatment. Overall response rate (≥PR) to PCD was 56% (5/9 pts), including 1 pt with a very good PR and 2 pts with complete responses (CR). Clinical benefit (≥minimal response, MR) was seen in 78% (7/9 pts). Of note, of the 3 pts with EM disease 1 achieved a CR and 1 a MR. Responses to PCD were fast and were achieved after a median of 2 cycles (range 1‐8). With a median follow up of 14 months, 6/9 patients have relapsed and 4/9 patients have died. Median duration of response was 2 months (range 0‐22), median PFS and OS were 7 and 16 months, respectively. Toxicities were limited, mainly neutropenia, which was easily manageable with G‐CSF.

Summary/Conclusion:

PCD is an effective regimen for pts relapsing or refractory to IMiDs, PI and daratumumab. The regimen seems particularly promising in patients with extramedullary disease, for whom treatment options are usually limited.