Thal-Dex Superior to VAD Before Transplant
Thal-Dex Superior to VAD Before Transplant
Abstract & Commentary
Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationships with this field of study.
Synopsis: In a case-control analysis, the combination of thalidomide-dexamethasone (Thal-Dex) was superior to vincristine-doxorubicin-dexamethasone (VAD) as induction prior to autologous stem cell transplant for multiple myeloma. The response rate was superior for Thal-Dex compared to VAD, at 76% vs 52%, respectively, with a similar CD34 stem cell yield of 7.85 × 106/kg and 10.5 × 106/kg, respectively. The study confirms the superiority of Thal-Dex over VAD and suggests the regimen may be considered standard induction therapy prior to autologous transplant.
Source: Cavo M, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicin-dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005;106: 35-39.
Although autologous stem cell transplantation (ASCT) remains standard care for eligible patients with multiple myeloma based upon randomized data, the landscape of choices for initial induction therapy has changed dramatically. The traditional upfront VAD regimen of vincristine-doxorubicin (Adriamycin)-dexamethasone has been challenged by a variety of new agents. In addition to the significant activity reported with thalidomide, lenalidomide (a thalidomide analogue) and bortezomib (a proteosome inhibitor), yield impressive responses in relapsed/refractory patients.
Cavo and colleagues report a large case-control study comparing either thalidomide-dexamethasone (Thal-Dex) or VAD, as initial therapy prior to peripheral blood autologous stem cell transplant. One hundred patients treated with Thal-Dex were closely matched with 100 controls treated with VAD. Both groups underwent similar mobilization and transplant regimens after 4 months of initial therapy.
Baseline characteristics demonstrated adequate matching. Comparing Thal-Dex to VAD showed the overall response rate was 76% vs 52% (P < .001), respectively and complete response rate was 10% and 8%, respectively. The Thal-Dex regimen also induced a better M protein response. In both groups, 9 patients did not undergo stem cell mobilization. Among the 91 patients that proceeded with mobilization and collection in each group, the collection product was similar at 7.85 × 106 for Thal-Dex compared to 10.5 × 106 for VAD (P = .4). Deep venous thrombosis, however, was increased in the Thal-Dex group at 15% overall and was 12% among the 81 patients treated with low-dose warfarin. Grade 3 or 4 neutropenia occurred in 12% on VAD compared to 0% on Thal-Dex.
COMMENTARY
Medical oncologists frequently initiate therapy for multiple myeloma, prior to evaluation for autologous stem cell transplantation. This matched case comparison of Thal-Dex and VAD for induction therapy prior to autologous stem cell transplant directly addresses this issue.
Although an observational study, the superior response rate demonstrated for the Thal-Dex arm compared to the VAD regimen is consistent with response difference for the ECOG randomized study of Thal-Dex compared to Dex reported in abstract form by Rajkumar et al (American Society of Hematology 2004, abstract 205) and prior data on response rate prior to transplant for Thal-Dex.1 Whether the non-significant but lower stem cell yields suggest Thal-Dex as an inferior mobilization regimen can not be established. However, the average collection of almost 8 × 106 CD34 cells/kg suggests most patients adequately collected for 2 transplants. The analysis includes no data on post-transplant outcomes, although one would expect the outcome to primarily hinge on response to induction therapy.
The increased myelosuppression with VAD and increased thrombosis risk with Thal-Dex comes as no surprise. While many consider Thal-Dex as standard initial therapy, clinicians may consider VAD in select patients at high risk of thrombosis. Ongoing studies with lenalidomide and bortezomib may eventually lead to displacement of thalidomide as initial therapy and relegate VAD to an historical footnote.
Reference
1. Abdelkefi A, et al. First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (< 61 years) with symptomatic multiple myeloma. Bone Marrow Transplant. 2005;36:193-198.
In a case-control analysis, the combination of thalidomide-dexamethasone (Thal-Dex) was superior to vincristine-doxorubicin-dexamethasone (VAD) as induction prior to autologous stem cell transplant for multiple myeloma. The response rate was superior for Thal-Dex compared to VAD, at 76% vs 52%, respectively, with a similar CD34 stem cell yield of 7.85 × 106/kg and 10.5 × 106/kg, respectively. The study confirms the superiority of Thal-Dex over VAD and suggests the regimen may be considered standard induction therapy prior to autologous transplant.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.