Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia

Musto, Pellegrino; Simeon, Vittorio; Martorelli, Maria Carmen; Petrucci, Maria Teresa; Cascavilla, Nicola; Raimondo, Francesco Di; Caravita, Tommaso; Morabito, Fortunato; Offidani, Massimo; Olivieri, Attilio; Benevolo, Giulia; Mina, Roberto; Guariglia, Roberto; D’Arena, Giovanni; Mansueto, Giovanna; Filardi, Nunzio; Nobile, Francesco; Levi, Anna; Falcone, Antonietta; Cavalli, Maide; Pietrantuono, Giuseppe; Villani, Oreste; Bringhen, Sara; Omedè, Paola; Lerose, Rosa; Agnelli, Luca; Todoerti, Katia; Neri, Antonino; Boccadoro, Mario; Palumbo, Antônio

doi:10.1038/leu.2013.241

Cited by 79 publications

(83 citation statements)

References 15 publications

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“…Additional 16 pPCL patients belonged to a prospective multicenter clinical trial (RV-PCL-PI-350, EudraCT N°2008-003246-28) [36]. All the patients included in this study have been previously described [33].…”

Section: Methodsmentioning

confidence: 99%

Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature

et al. 2016

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The prevalence of TP53 mutations greatly varies between tumor types; in multiple myeloma (MM) they were rarely detected at presentation, while increased frequency was reported with disease progression. Using next-generation sequencing, we analyzed TP53 exons 4-9 in a large representative cohort comprising patients with MM at diagnosis and more aggressive forms of plasma cell (PC) dyscrasia, identifying mutations in 4/129 (3%) MM, 6/24 (25%) primary PC leukemia, and 2/10 (20%) secondary PC leukemia cases. A similar increase in prevalence associated with disease aggressiveness (5%, 29.2% and 44%, respectively) was observed for TP53 deletion. Interestingly, in five patients mutations were not concomitant with TP53 deletion. Furthermore, longitudinal analysis revealed the acquisition of TP53 mutations in three of nineteen cases analyzed at relapse. Identified variants were mostly missense mutations concentrated in the DNA binding domain, only partly reflecting the pattern globally observed in human cancers. Our data confirm that TP53 mutations are rare in MM at presentation and rather represent a marker of progression, similarly to del(17p); however, their occurrence even in absence of deletions supports the importance of their assessment in patients with PC dyscrasia, in terms of both risk stratification and therapeutic implications.

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Section: Methodsmentioning

confidence: 99%

Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature

et al. 2016

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“…Recently, Musto et al [22] conducted a first prospective trial of lenalidomide and dexamethasone therapy in a series of previously untreated pPCL patients, and they indicated that the median OS was 28 months after a median follow-up of 34 months. It is noteworthy that the OS was not reached in patients eligible for or treated with HSCT.…”

Section: Discussionmentioning

confidence: 99%

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

Iriuchishima

Ozaki²,

Konishi³

et al. 2015

Acta Haematol

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We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Gonsalves¹,

Rajkumar

Go³

et al. 2014

Blood

113

100

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Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia

Cited by 79 publications

References 15 publications

Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature

Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature

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

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

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