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

Abstract

The present study aimed to evaluate the side-effects and efficacy of thalidomide in combination with an anthracycline-containing chemotherapy regimen in previously untreated myeloma patients. Thalidomide (400 mg/d) was combined with bolus injections of vincristine and epirubicin and oral dexamethasone (VED). Chemotherapy cycles were repeated every 3 wk until no further reduction in myeloma protein was observed, whereas the treatment with thalidomide was continued until disease progression. Thirty-one patients were enrolled, 12 patients were exclusively treated with thalidomide in combination with VED and 19 patients additionally received high-dose melphalan, for consolidation. Adverse events and response to therapy were assessed prior to treatment with high-dose chemotherapy. Response to thalidomide combined with VED was complete remission in six patients (19%), partial remission in 19 patients (61%), stable disease in five patients (16%), and progressive disease in one patient (3.2%). Grade 3 and 4 adverse events consisted of leukocytopenia in 10 patients (32%), and thrombocytopenia and anemia in one patient each (3.2%). Neutropenic infections grade 3 and 4 occurred in seven (23%) and three patients (9.7%), respectively, including two patients (6.5%) who died from septic shock. Deep vein thrombosis occurred in eight patients (26%), constipation in 20 patients (65%), and polyneuropathy in 20 patients (65%). The probability of event-free survival and overall survival in the whole group of patients at 36 months were 26 and 62%, respectively. In conclusion, the combination of thalidomide with VED appears to be highly effective in previously untreated patients with multiple myeloma, but it is associated with a high rate of thrombotic events, polyneuropathy, and neutropenic infections.

Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma

“…on May 9, 2018. by guest www.bloodjournal.org From lowest rates reported by other studies, [10][11][12][13]18 it needs to be reduced. Even though the best DVT prophylaxis in patients receiving thalidomide-based regimens has not been established so far, retrospectively, we believe that fixed-dose warfarin might have been inadequate as DVT prophylaxis in our protocol.…”

“…8 Better results can be obtained when chemotherapeutic agents are added to or administered before 18 the thalidomide-dexamethasone combination. [10][11][12][13] At present, it remains unclear which single or other chemotherapy regimen is the best one to be combined with thalidomidedexamethasone to achieve a higher CR rate associated with an acceptable toxicity. Moreover, it is unknown whether the best quality of response obtained with these combinations does affect survival parameters of patients with MM.…”

“…Administered as a single agent, 5 in combination with dexamethasone, [6][7][8][9] or with conventional chemotherapy, [10][11][12][13] it has been found to offer very promising results in untreated patients with MM. In particular, the best results were observed when thalidomide was combined with melphalan 13 or with antracyclines, [10][11][12] although the toxicity of these combinations was severe and withdrawals from study protocols were frequent also in younger patients. However, it is yet unclear what is the better agent or agents or regimen or regimens to combine with thalidomide-dexamethasone to improve their efficacy minimizing the toxicity, especially in older patients.…”

Recent major improvement in long-term survival of younger patients with multiple myeloma

“…[21][22][23] After the approval of thalidomide for the treatment of MM, 2 further treatment options have appeared. A thalidomide analog known as lenalidomide, which is effective in vitro at lower concentrations than thalidomide and is potentially less toxic, was developed.…”

Thrombotic Complications of Myeloma Therapy

“…As shown in Table 2, in phase II studies evaluating thalidomide plus anthracycline-containing chemotherapy regimens without thromboprophylaxis, incidences of 10% to 58% have been reported. 5,[33][34][35] The study with the highest reported incidence of TEE was a large phase II trial evaluating DVd-T in both RRMM and NDMM patients in which 58% of patients developed TEE prior to amendment of the protocol mandating low-dose aspirin thromboprophylaxis. As will be discussed in more detail below, the addition of ASA reduced the incidence of TEE by approximately two-thirds.…”