Lenalidomide (Revlimid), Bortezomib (Velcade) and Dexamethasone (RVD) For The Treatment Of Secondary Plasma Cell Leukaemia

Secondary plasma cell leukemia (SPCL) is an aggressive variant of multiple myeloma (MM) characterized by the presence of >20% and/or an absolute number of >2 × 10⁹/L circulating PCs cells in the peripheral blood. Recently, combinations of bortezomib (bor) or lenalidomide (len) with conventional cytotoxic  drugs have demonstrated very high rates and quality of response in MM, and, based on this data, we aimed to assess the efficacy of len, bor and dexamethasone (RVD) in SPCL.

Methods

In this retrospective study, we reviewed the records of all patients (pts) with SPCL treated with RVD at Princess Margaret Cancer Center between 03/09 and 06/12. A total of 9 pts were identified. Pts received oral len 10-15 mg/d on days 1-14 (dose adjusted for creatinine clearance), bor 1.0 or 1.3 mg/m² on days 1, 4, 8, and 11 of 21-day cycles (in 3 pts) and once weekly (in 6 pts) along with dexamethasone (20 mg or 40 mg weekly). Primary endpoints were response rate, progression-free survival (PFS), overall survival (OS), and toxicity.

Results

Clinical characteristics are showed in Table 1. Pts had received a median of 3 lines of therapy (1-5).  Thalidomide, len and bor containing regimens were previously used in 3, 5 and 7 pts respectively. After a median of 3 cycles (1-14), CR was seen in 1, VGPR in 2, PR in 1 and 5 pts progressed while on therapy. Pts who achieved ≥ PR experienced a significantly better PFS (11.67 versus 1.57 months) (p=0.0049). At the time of analysis all of the cases had progressed and died. The median PFS was 5.23 months (range 1.68-31.53) with 2 pts progressing after 27 months. Median OS for the entire group was 5.13 months (range 1.17-32). Furthermore, median OS was significantly longer for pts achieving ≥ PR compared to those who did not (7.93 versus 2.93 months, p=0.0472). The median time to first and best response was 4 and 8 weeks, respectively. Two pts (22.2%) experienced non-hematological grade 3/4 adverse events, including sepsis and pneumonia. Grade 3 and 4 neutropenia and thrombocytopenia occurred  in 6 pts, and 3 pts required G-CSF to avoid treatment delays.

In conclusion

we demonstrated that the combination of RVD is able to obtain responses in 44% of in SPCL cases within one month of therapy. Although the median PFS was only 5.23 months, 2 pts experienced responses exceeding 2 years. Thus, we recommend trying RVD for 1 cycle; if no response is seen, an alternative approach should be utilized. Newer agents such as pomalidomide and carfilzomib should be investigated in this aggressive disease in which the majority of responses are short-lived.

Reece:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Millennium Pharmaceuticals: Research Funding; Novartis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; BMS: Research Funding; Otsuka: Honoraria, Research Funding; Onyx: Consultancy. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Kukreti:Millennium Pharmaceuticals: Research Funding; Onyx: Research Funding.