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

Abstract

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomibbased 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 5 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.

Novel Agents for the Treatment of Primary Plasma-Cell Leukemia: Lights and Shadows

“…Overall, these results are quite similar to those observed in previous retrospective studies, the most numerically relevant including a total of 54 PPCL patients; here, the use of bortezomib-based regimens was associated with an ORR of 79-89% and a very good partial response rate of 33-38%, resulting in an OS of 55% after 24 and 18 months of follow-up, respectively [4,5]. The adjunct of ASCT was strongly associated with a better outcome in the Italian study [4], whereas in the Greek experience, treatment with a bortezomib-based regimen and a high-quality response were the only powerful predictors for survival [5].…”

“…The adjunct of ASCT was strongly associated with a better outcome in the Italian study [4], whereas in the Greek experience, treatment with a bortezomib-based regimen and a high-quality response were the only powerful predictors for survival [5]. Similarly, in the only prospective trial so far performed on PPCL, conducted with a combination of lenalidomide and low-dose dexamethasone with/without ASCT, in a consecutive series of 23 newly diagnosed PPCL patients [6], intention-to-treat ORR was 74% and at least the very good partial response rate was 39%.…”

Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma

“…The ORR was 79%, and 55% of the patients were alive after a median follow-up of 24 months. Katodritou et al [14] studied 25 pPCL patients, 19 of whom were treated with novel agents, including bortezomib and thalidomide, and five of whom received HSCT. The ORR was 69% and the median OS was 16 months.…”

Trends in survival of patients with primary plasma cell leukemia: a population-based analysis

“…21 Recent single-institution studies suggest an improvement in OS among pPCL patients when novel agents have been incorporated upfront in their treatment. [14][15][16][17][18] The wide availability of novel agents began in 2001; however, this was initially approved in the relapsed setting alone and it was not until 2006 that these agents began to gain approval for use in the first-line setting. Ramsingh et al assessed the outcomes of pPCL during 1973-2004 using the SEER 17 database but were unable to detect an improvement in OS with time.…”

“…1,[10][11][12][13] However, recent retrospective studies suggest that the incorporation of novel agents as well as ASCT in treating pPCL has improved the median OS to more than 24 months. [14][15][16][17][18][19] Given the lack of large, prospective studies evaluating the survival outcomes in pPCL because of its rarity, we used the Surveillance Epidemiology and End Results (SEER) program to evaluate the survival trends in pPCL patients in the US population during various time intervals based on the availability of ASCT and novel agent therapy.…”