The efficacy and safety of the PAD regimen (bortezomib, doxorubicin, dexamethasone) in the treatment of plasma cell leukemia

Plasma cell leukemia (PCL) represents the most aggressive variant of multiple myeloma that requires establishing new treatment approaches. Here, we report 4 patients with PCL treated with bortezomib. In 3 patients primary PCL and in one - secondary PCL was diagnosed. Two patients had previously received 2 to 4 lines of chemotherapy, including thalidomide and two patients received only VAD treatment. Bortezomib was given according to the standard schedule of 1.3 mg/m2 days 1,4,8,11 with an interval of 10 days between the cycles. Three patients received doxorubicin 9 mg/m2 and dexamethasone 40 mg on days 1-4 of cycle in combination with bortezomib (PAD regimen). In the first patient with primary PCL (with bone marrow plasma cell ratio - 80%, absolute peripheral blood plasma cell count- 3.7 x 109/L cells, IgGλ serum monoclonal protein 8.5 g/dL and osteolysis) bortezomib was administered twice as an induction therapy and was re-administered in relapse. A near complete remission (disappearance of circulating and bone marrow plasma cells, disappearance of M-component at electrophoresis but positive immunofixation) was achieved subsequently to induction PAD treatment. In this patient herpes zoster and neurological grade 2 toxicity was observed. Following cyclophosphamide 4.9 g and G-CSF, peripheral blood stem cells were successfully (8.0 x 106 CD34+ cells/kg) harvested. After melphalan 200 mg/m2 peripheral blood autologous stem cell transplantation (PBASCT) was performed. The time to neutrophil > 0.5 x 109/L engraftment was 20 days and the time to platelet count > 20 x 109/L was 17 days. PBASCT led to complete remission which lasted 7 months. Partial remission was achieved subsequently to PCL relapse retreatment with PAD which was accompanied by hematological toxicity, infections and aggravation of peripheral sensory neuropathy. The patient died of progressive disease 27 months from PCL diagnosis and 8 months from its recurrence. In the second case of primary PCL with renal failure requiring hemodialysis and severe thrombocytopenia after PAD treatment a partial response with improvement of renal function and increase in platelet count was achieved. After 8 cycles of PAD, 16 months from PCL diagnosis, the patient feels good. The third patient with recurrence of primary PCL after 33-month remission achieved with conventional chemotherapy, died of progressive disease after completing 2 cycles of bortezomib. In the fourth patient with secondary PCL bortezomib therapy was discontinued after one cycle due to severe motory died of progressive disease after completing 2 cycles of bortezomib. In the fourth patient with secondary PCL bortezomib therapy was discontinued after one cycle due to severe motory neuropathy. The two latter patients survived 46 and 2 months, respectively, from the moment of PCL diagnosis. Our experience suggests that combination chemotherapy with bortezomib, doxorubicine and dexamethasone, in the form of the PAD regimen, may be an effective induction treatment for primary PCL and does not prejudice peripheral blood stem cell collection or subsequent engraftment. (authors)