Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT

Abstract

Summary:Several trials have shown the activity of thalidomide (THAL) in relapsed multiple myeloma (MM) patients failing PBSCT or conventional chemotherapy. PBSCT is considered standard treatment for most patients requiring therapy for MM; however, patients with VAD-resistant disease may not be able to receive PBSCT due to rapidly advancing disease. We report four cases of VAD-refractory MM salvaged with THAL ؉ VAD followed by PBSCT. All patients underwent stem cell mobilization with cyclophosphamide (Cy) (4.5 g/m 2 ) and GMCSF. Melphalan (140-200 mg/m 2 ) was given as conditioning. All patients engrafted within 12-16 days after PBSCT. Day ؉100 evaluation showed the following: very good partial response (n ‫؍‬ 1) and complete response (n ‫؍‬ 3). After a median follow-up to 153 days, two patients continue to take THAL with no signs of disease progression. One patient developed CHF and was taken off THAL while another patient has died of progressive disease while on THAL (MTD 50 mg). In conclusion, VAD-refractory patients were salvaged with the addition of THAL to VAD. They were subsequently able to undergo autologous PBSCT for MM, which will likely improve their overall survival. This suggests that THAL and other related immunomodulatory drugs may prove useful for initial MM therapy in combination with standard chemotherapy followed by PBSCT. Bone Marrow Transplantation (2002) 29, 577-580. DOI: 10.1038/sj/bmt/1703522 Keywords: multiple myeloma; peripheral blood stem cell transplantation; thalidomide VAD (vincristine, adriamycin, dexamethasone) is considered standard, first-line therapy for multiple myeloma (MM). 1,2 Patients who develop VAD-refractory disease are at high risk for mortality due to progressive disease. Single agents such as cytosine arabinoside (Ara-C) have only modest activity against VAD-refractory multiple myeloma. 3 In addition, different combination chemotherapy regimens have limited effect. These include vincristine and etoposide, etoposide, dexamethasone, Ara-C and cisplatin (EDAP) and DAP alone. 4,5 The hyper C-VAD regimen (twice daily cyclophosphamide (Cy) and VAD) produced a 40% response rate and a median remission duration of only 8 months in VAD-refractory MM patients. 6 Thus new approaches are necessary to treat MM refractory to standard treatment.Thalidomide (THAL) is a novel anti-myeloma agent with 25 to 35% response rates in heavily pre-treated patients. 7,8 Singhal et al 7 reported the results of 84 patients with previously treated and progressive MM who were treated with THAL as a single agent. Ten percent of patients had complete or nearly complete remission (CR) and 32% had a reduction in serum or urine paraprotein level of at least 25%. After 12 months of follow-up, 22% of the study patients remained event free and 58% were alive. Juliusson et al 8 reported the results of 23 advanced and heavily pretreated MM patients who were treated with THAL. Ten of 23 (43%) achieved a partial response (PR) and six had minor responses (MR) or stable disease (SD).There is clear evidence suppor...

Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield

“…The HOVON-50-data showed a median time to leukapheresis in TAD patients of 11 days (7-52) and 11 days (9-24) for VAD patients. In line with our results, Ghobrial et al 17 showed no difference between Thal and control group regarding the number of days of leukapheresis, but they remarked that patients from the Thal group were not likely to collect sufficiently in 1 day, similar to the group of Ahmad et al 18 who administered Thal continuously during leukapheresis. In contrast, Desikan et al 10 …”

“…Importantly, no difference was found in the recovery of WBC, ANC or PLT in either VAD or TAD after first ABSCT (Table 4). Similarly, Ahmad et al 18 showed that hematopoetic reconstitution (ANC40.5 Â 10 9 /l, PLT 420 Â 10 9 /l) occurred between 12 and 16 days after ABSCT, pretreated with VAD and Thal. We next investigated if an influence could be seen on the number of PLT or red blood cells (RBC) transfused during engraftment time, and no difference was found in both treatment groups.…”

Thalidomide in combination with vincristine, epirubicin and dexamethasone (VED) for previously untreated patients with multiple myeloma

“…Similar to other trials (27, 38, 39), our study shows that the combination of thalidomide with chemotherapy does not have a negative impact on mobilization and collection of PBSC, as found in the 20 patients who were candidates for autologous PBSCT. In the 17 of the 19 patients (89%) who actually received high‐dose chemotherapy with PBSCT, a normal recovery of peripheral blood cell counts was observed despite continuous treatment with thalidomide.…”

An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma

“…It has been confirmed by many study groups that THAL as a single agent (Dmoszynska et al, 2000;Patriarca et al, 2003) or combined with VAD (Ahmad et al, 2002;Pitini et al, 2003) could be a suitable bridging regimen to PBSC collection and autologous SCT for VAD-refractory MM patients. Moreover, Ghobrial et al (2003) showed that THAL does not substantionally affect peripheral blood mobilisation or engraftment, which is in line with our observation.…”