VASP Chemotherapy in Patients with Multiple Myeloma.

Introduction: Multiple myeloma (MM) is a malignant disorder of plasma cells resistant to chemotherapy. Various chemotherapy protocols are available for patients with MM, including VAD (vincristine, adriamycin, prednisolon) and MP (melphalan, prednisolon). These therapies aim to slow disease progression and/or prepare the patient for stem cell transplantation (SCT), the standard of care for MM patients younger than 70. An additional regimen, VASP, consisting of etoposide 50mg/m² IV on day 1 and 100mg/m² PO on days 2–4, adriamycin 25mg/m² IV on day 1, cyclophosphamide 500mg/m² IV on day 1 and dexamethasone 40mg PO qd on days 1–4, has been used in Iceland for the past 18 years. Due to the advantage of outpatient administration of VASP compared to VAD (96 hour hospital admission or indwelling venous access device with risk of extravasation), VASP has increasingly become the preferred chemotherapeutic regimen for Icelandic MM patients. Although our experience shows that VASP is comparable to VAD with respect to efficacy and toxicity, we are unaware of previous studies in support of this. The aim of this study was therefore to evaluate the efficacy and toxicity of VASP chemotherapy as it has been used in Iceland.

Patients and methods: Medical records of all MM patients treated with VASP chemotherapy over a 15-year period (1990–2004) were retrospectively analyzed. Baseline disease characteristics were assessed, as was information about disease progression and previous therapy. Response to VASP (CR, PR and NR; EBMT criteria) and toxicity was documented. Survival was evaluated by the Kaplan-Meier method.

Results: Of the 26 patients receiving VASP chemotherapy, 22 (12 male, 10 female) were included in this study (4 records incomplete or absent). Mean age was 64 years (range 35–86). 14 patients had IgG, 7 IgA, and 1 patient had no measurable paraprotein. 15 of the 22 patients had previously been treated with 1–2 courses of chemotherapy including VAD. Each patient received on average 5,3 courses of VASP (range 1–11). A response was seen in 17 patients (77.3%) (2 CR, 15 PR) and 5 (22,7%) showed no response. Three patients not responding to initial VAD therapy demonstrated a subsequent PR to VASP. Of the 22 patients, 15 died during the 15 years of study, resulting in a mean overall survival (OS) of 3,8 years (0,9–10,5) from diagnosis of MM and 2,0 years after VASP therapy (0–3,4). 33 of 116 VASP courses resulted in hospitalization (28,4%). Neutropenia was seen after 38,8% of the courses (nadir 0.5 x 10⁹/L; 77.3% after the first course) and G-CSF was used in 56% of cases. Neutropenic fever was seen after 10.6% of courses and infection was documented in 15,5% of patients (bacteremia 13.6%). Transfusion of PRBC’s was required after 25 of the 116 courses but platelets after only three.

Conclusion: We present data supporting the efficacy and safety of VASP chemotherapy for MM patients. Our total response rate of 77,3% compares favorably with other therapies such as VAD, and survival and toxicity is also comparable to other therapies. Although small, this is the first study we are aware of on VASP therapy for MM. Further studies, preferably larger and prospective, are required to confirm the efficacy and toxicity of VASP chemotherapy for MM.