Bortezomib Plus Dexamethasone As Induction Treatment Followed by Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma: A Study From India

Multiple myeloma (MM) is an incurable hematological malignancy, afflicting 25000 patients each year in India. Complete remission in myeloma is a surrogate marker for improved survival. The objective of induction regimen, using novel agents such a bortezomib, and Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) is to increase the number of patients achieving CR. Here, we report a retrospective evaluation of the efficacy and response rates of induction with Bortezomib (Velcade) plus Dexamethasone (VD Regimen) followed by APBSCT and its effect on stem cell collection and final outcome of the transplant.

Ten patients with symptomatic MM who had received VD induction before stem cell collection were evaluated. VD Induction comprised of Bortezomib (1.3 mg/m²) and Dexamethasone (40 mg) administered on days 1, 4, 8, 11 for four 21-day cycles.

Peripheral blood stem cell collection technique involved administration of granulocyte stimulating factor (G-CSF); 300 mg/kg administered twice daily for 5 days. Adequate number of stem cells was collected in nine patients by a single harvest. One patient required apharesis twice for adequate stem cell collection. These cells were cryo-preserved. High dose Melphalan (200 mg/m²) was given followed by stem cell transfusion.

The median CD34-positive stem cell count was 5.6 × 10⁶/kg. All the patients engrafted post transplant. The median time for engraftment i.e. Absolute Neutrophil Count (ANC) > 500/mL was 10 days and Platelet Count > 50000/mL was 16 days. The median length of hospital stay was 21 days. They were successfully managed for fever and infections with antibiotics, antifungals and supportive treatment. Irradiated blood (median - 4 units) and platelet apharesis (median – 3 units) were given.

Response was assessed according to International Myeloma Working Group uniform response criteria. After induction with VD protocol, the overall response rate (ORR) was 90%. 2 patients (20%) had a complete response (CR), 7 patients (70%) had very good partial response (VGPR) and 1 patient (10%) had progressive disease.

Post – APBSCT, the patient with progressive disease achieved VGPR and 6 out of 7 patients (85.7%) with VGPR achieved CR making the total responses as 8 CRs and 2 VGPRs. Thus, ORR was 100%, including 80% CR rate and 20% VGPR rate.

All patients were put on maintenance therapy, 6 patients were on thalidomide (50 mg/day) and 4 patients received lenalidomide (10 mg/day) therapy.

In the analysis, the median progression-free survival (PFS) was not reached at 22 months. The median overall survival (OS) was not reached after a median follow-up of 25 months, and the 2-year OS rate was 70%. Three patients (30%) had a relapse post-APBSCT, after 5 months, 9 months and 18 months respectively. Two patients (20%) expired, one due to myeloma and the other due to unrelated cause. All three patients with renal insufficiency experienced improvement in renal function and did not require dialysis post-APBSCT. Two patients (20%) developed neuropathy and two patients (20%) developed Herpes Zoster infection due to bortezomib therapy.

The induction regimen of bortezomib plus dexamethasone is effective and well tolerated in symptomatic myeloma patients. It significantly improves post-induction and post-transplantation CR and VGPR rates and does not affect stem cell mobilization and collection procedure.

No relevant conflicts of interest to declare.