Treatment with bortezomib-based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group.

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib-based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL-pPCL and 17 with secondary PCL-sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR-group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow-up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow-up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity.

Clinical features, outcome, and prognostic factors for survival and evolution to multiple myeloma of solitary plasmacytomas: a report of the Greek myeloma study group in 97 patients.

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) ± surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P = 0.2). The 5- and 10-year MM-free survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P = 0.054). Overall, the 5- and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T.

Response of primary plasma cell leukemia to the combination of bortezomib and dexamethasone: do specific cytogenetic and immunophenotypic characteristics influence treatment outcome?

Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasias. Its special biological characteristics may play an important role in the poor outcome when treated with conventional therapy or even with stem cell transplantation. New treatment approaches based on the biology of this disease are mandatory. Here we present three cases of primary PCL with adverse cytogenetics (deletion 13q14 and translocation 4;14) and specific immunophenotypic features (CD27 antigen strong expression) in which excellent response and sustained remission was achieved with the combination of bortezomib and dexamethasone. The possible role of these biological characteristics is been analyzed.

Successful treatment of extramedullary gastric plasmacytoma with the combination of bortezomib and dexamethasone: first reported case.

We report a case of a 68-year-old man presented with upper-gastrointestinal bleeding. Endoscopy showed a large ulcerated gastric mass. Histological examination of the gastric biopsies revealed a k monoclonal extramedullary plasmacytoma (EMP). Further staging was negative for multiple myeloma. The patient was managed with bortezomib at a dose of 1.3mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle in combination with dexamethasone 20mg p.o. on days 1, 2, 4, 5, 8, 9 and 11, 12 of each cycle. After 4 cycles of treatment, no endoscopic or histological findings of EMP were found. Thirteen months after diagnosis the patient is in complete remission with no evidence of local relapse or evolution to multiple myeloma. This is the first reported case of EMP successfully managed with the combination of bortezomib and dexamethasone.

Erythropoiesis-stimulating agents are associated with reduced survival in patients with multiple myeloma.

The impact of erythropoiesis-stimulating agent (ESA) on cancer patients' survival has recently become a matter of extensive discussion. Studies in solid tumors demonstrated that ESA adversely affects survival. This issue has not been sufficiently studied in patients with multiple myeloma. In this study, which included 323 multiple myeloma patients followed in our Institution between 1988 and 2007, we demonstrated by using a proportional hazards model including multiple covariates (age, LDH, Hb, platelets, serum creatinine, ISS score, beta2 microglobulin, and ESA administration) that ESA administration is associated with reduced survival (hazards ratio: 1.88, 95% CI: 1.28-2.77). Anemia, which is considered a predictor for survival, platelets, serum creatinine, ISS score, and LDH, were not significant, whereas, age and beta2 microglobulin confirmed their predicting value in the multivariate analysis. With a median follow-up of 31 months (range 1-238), the median survival of patients in the ESA group was 31 months (95% CI: 25-37), whereas in the group without ESA administration it was 67 months (95% CI: 55-79) (P < 0.001). The median progression-free survival for patients in the ESA group was 14 months (95% CI: 12-16), and for the group without ESA it was 30 months (95% CI: 24-36) (P < 0.001). These results indicate that ESA may have a detrimental impact on MM patients' outcomes and, thus, in this context, they should be used with rigorous criteria.