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

Abstract

In a phase III randomized, multicenter study, the Germanspeaking Myeloma-Multicenter Group (GMMG) and the DutchBelgian Hemato-Oncology Cooperative Group (HOVON) group investigated the influence of thalidomide (Thal) on the outcome of peripheral blood stem cell (PBSC) collection in multiple myeloma (MM) before peripheral autologous blood stem cell transplantation (ABSCT). We analyzed the data of 398 myeloma patients after induction with Thal, doxorubicin and dexamethasone (TAD) in comparison with vincristine, doxorubicin and dexamethasone (VAD) followed by mobilization with cyclophosphamide, doxorubicin, dexamethasone (CAD) and PBSC collection. Within both the study groups, patients treated with TAD showed to collect significantly fewer CD34 þ cells compared with VAD (GMMG, TAD: median 9.8 Â 10 6 /kg; range 2.0-33.6; VAD: median 10.9 Â 10 6 /kg range 3.0-36.0; P ¼ 0.02) (HOVON, TAD: median 7.4 Â 10 6 /kg; range 2.0-33.0; VAD: median 9.4 Â 10 6 /kg; range 0.0-48.7; P ¼ 0.009). However, engraftment after peripheral autologous stem cell transplantation showed no difference between Thal and VAD groups. We conclude that Thal as a part of induction regimen is associated with better response rates (GMMG-HD3: CR/PR 79%, VAD: CR/PR 58%; HOVON-50: TAD: CR/PR 81%, VAD: CR/PR 61%), but significantly affects the yield of PBSC collection. Nevertheless, the number of total CD34 þ cells collected was sufficient for double autologous transplantation in 82% of the Thal patients, with at least 2.5 Â 10 6 /kg CD34 þ cells.

Bisphosphonates do not delay engraftment after autologous SCT in patients with newly diagnosed myeloma

“…Regarding the impact of the initial treatment on engraftment post ASCT, controversial results have been published. 2,3 In our study, a delayed engraftment in patients previously treated with Thal-Dex was observed.…”

Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma

“…Several retrospective studies as well as the data from prospective clinical trials where thalidomide had been added to conventional therapies have provided conflicting data. Recently, Breitkreutz et al 23 reviewed the data from two prospective clinical trials that compared traditional VAD to a combination of thalidomide, doxorubicin and dexamethasone (TAD). Patients were mobilized with cyclophosphamide, doxorubicin, dexamethasone (CAD) followed by G-CSF.…”

“…There remains some controversy regarding the effect of thalidomide on stem cell collection and engraftment with studies showing discordant results. [23][24][25][26] Unlike thalidomide and dexamethasone, marrow suppression is a prominent adverse effect of lenalidomide (Rajkumar SV et al Blood 2006; 108: 799, abstract). The regimen of lenalidomide and low-dose dexamethasone have been associated with one of the lowest initial mortality rate following diagnosis of myeloma and this coupled with the ease of an oral regimen has resulted in this regimen's widespread use as induction therapy.…”

Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma

“…4,5 Thalidomide is not generally myelosuppressive and in large studies, stem cell collection numbers were only modestly lower than that seen with VAD chemotherapy, with 84% of patients collecting sufficient stem cells for tandem transplant. 6 Promising results on the use of lenalidomide and dexamethasone have resulted in a recommendation for the use of this combination in newly diagnosed patients heading for transplant. 7 However, one recent analysis of stem cell collection following lenalidomide induction indicated that stem cell collection yields are compromised in some patients.…”