Bortezomib and Plasma Cell Leukemia.
Authors: Musto Pellegrino , Barone Marialucia , Guariglia Roberto , Pietrantuono Giuseppe , Gay Francesca , Rossini Fausto , Guglielmelli Tommasina , Pitini Vincenzo , Ferrara Felicetto , Galli Monica , Falcone Antonietta , Pozzi Samantha , D’auria Fiorella , Sacchi Stefano , Boccadoro Mario , Palumbo Antonio 
Published: October 2019

Abstract
Bortezomib (Velcade) is currently approved in USA and EU for the treatment of resistant/relapsed multiple mieloma (MM). Some reports have suggested that bortezomib is particularly effective for the treatment of extramedullary MM. However, there are very few data about the efficacy of this drug in plasma cell leukemia (PCL), a MM variant usually characterized by very poor prognosis.
We retrospectively evaluated 9 patients with PCL diagnosed between October, 2002, and May, 2006, who had received bortezomib for the treatment of their disease (6 males, 3 females; median age 63 years, range 55–74). Six patients had primary and 3 secondary PCL. Eight patients had previously received 1 to 4 lines of chemotherapy, including autologous transplantation (5) and thalidomide (4). One patient was treated at diagnosis. Circulating plasma cells ranged from 2 to 71 x 10e9/L. Median WBC count was 23 x 10e9/L (range 8.1–113). Two patients had a moderate degree of renal failure, 3 had extramedullary disease (jaw, liver, soft tissues). Del 13 was observed in 4 out of 5 patients with available karyotype.
Bortezomib was given using the standard schedule of 1.3 mg/sqm days 1, 4, 8, 11, with an interval of 10 days between cycles. Two patients received dexamethasone and thalidomide, 1 thalidomide alone and 3 doxorubicin and dexamethasone in combination with bortezomib. A median of 4 cycles was administered (range 2–6). Grade 3–4 hematological toxicity occurred in 7 patients, while neurological grade 3 toxicity was observed in a single patient. Infections (grade 3) occurred in 4 patients. Other toxicities (diarrhoea, nausea, skin rash) never reached grade 3. Three patients required red cell and/or platelet support. In 3 subjects a reduction of bortezomib dose was required due to hematological or neurological toxicity.
Four partial remissions (reduction of M-component > 50%), 3 near-complete remissions (disappearance of M-component at electrophoresis, but positive immunofixation) and 2 complete remissions (negative immunofixation) were achieved (100% overall response), whose duration ranged from 2 to 14 months. In 4 patients autologous transplant procedures were started after response induced by bortezomib. Eight patients are currently alive 7–45 months after diagnosis of PCL. One patient, who had interrupted the treatment after 2 cycles due to herpes zoster, died of progressive disease 7 months later.
Our data indicate that bortezomib is very effective in inducing significant responses in patients with primary or secondary PCL and that this drug should be considered for the initial treatment of this disease. Curiously, during the review work, we recorded 3 cases of PCL developed in MM patients under salvage therapies including bortezomib. This intriguing finding, which strongly contrasts with the very good results obtained in patients with previously established PCL, would warrant to be further investigated with “ad hoc” studies.