PROGNOSTIC SIGNIFICANCE OF PLASMABLASTIC PLASMA CELLS IN THE ERA OF NOVEL AGENTS IN MULTIPLE MYELOMA
(Abstract release date: 05/18/17)
EHA Library. Machet A. 05/18/17; 182701; PB1987
Antoine Machet
Contributions
Contributions
Abstract
Abstract: PB1987
Type: Publication Only
Background
Plasmablastic (PB) feature of plasma cells in multiple myeloma (MM) has long been identified as poor prognosis. Interestingly it does not take part of International Revised Scoring System (R-ISS). Similarly, the prognostic impact in the era of novel agents and novel classes in MM is unknown. Finally, the percentage of PB in the bone marrow to which a poor prognosis develop is unclear.
Aims
To assess which modality of treatment of plasmablastic MM was associated with longer progression free survival (PFS) and overall survival (OS).
Methods
We have performed a retrospective analysis of all MM in our center from May 2005 to November 2016, and sought for MM with plasmablastic features, characterized by immature cells with high proliferative index rate. The PFS and OS were calculated since the first time the PB morphology was observed in the bone marrow aspiration, at the outset in newly diagnosed patients or in relapsed patients.
Results
65 patients with PB were included. Adverse cytogenetic per IMWG criteria was reported in 6 patients, del17p x3, t(4;14) x3, and one with both. 33,8% were ISS 3, and 23,1% R-ISS 3. Extramedullary disease (EMD) was reported in 40%. 35 patients (53,8%) were in first-line therapy.
The overall response rate with any triplet-based treatment containing always a proteasome inhibition and IMIds or alkylator was 49,2%, with 29,2% VGPR and 4,6% CR. The median PFS and OS were 6,9 and 14,9 months as a whole, respectively. The median PFS was greater when treatment combined bortezomib, lenalidomide and dexamethasone: 36,1 months ([0-99] vs 5,5 [0,59-10,4] otherwise; p=0,014). However, no difference in OS was demonstrated. Importantly, high dose therapy with ASCT was associated with longer PFS and OS, respectively 21,4 months ([12,8-30,1] vs 2,83 [0-5,7] p=0,003) and 50,4 months ([29,9-70,7] vs 6,27 [1,1-11,4] p=0,001). In multivariate analysis, poor OS was associated to acute renal failure at disease entry, presence of EMD, of del(17p), of hypercalcemia, and elevated lactate dehydrogenase.
We then sought to demonstrate that use of a direct anti proliferative-based agent such as anthracycline would participate to rapid disease reduction and PB clone control. It turns out that there was no significant difference in terms of survival in patients treated with an anthracycline-based regimen.
Conclusion
this study confirms the poor prognosis of PB feature in MM. A triple-based association with a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) seems to provide the best PFS in MM with PB, ideally complemented by ASCT. The role of anthracycline remains to be demonstrated. This data will be validated in a large cohort.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Treatment, Survival, Plasma cells, Multiple Myeloma
Abstract: PB1987
Type: Publication Only
Background
Plasmablastic (PB) feature of plasma cells in multiple myeloma (MM) has long been identified as poor prognosis. Interestingly it does not take part of International Revised Scoring System (R-ISS). Similarly, the prognostic impact in the era of novel agents and novel classes in MM is unknown. Finally, the percentage of PB in the bone marrow to which a poor prognosis develop is unclear.
Aims
To assess which modality of treatment of plasmablastic MM was associated with longer progression free survival (PFS) and overall survival (OS).
Methods
We have performed a retrospective analysis of all MM in our center from May 2005 to November 2016, and sought for MM with plasmablastic features, characterized by immature cells with high proliferative index rate. The PFS and OS were calculated since the first time the PB morphology was observed in the bone marrow aspiration, at the outset in newly diagnosed patients or in relapsed patients.
Results
65 patients with PB were included. Adverse cytogenetic per IMWG criteria was reported in 6 patients, del17p x3, t(4;14) x3, and one with both. 33,8% were ISS 3, and 23,1% R-ISS 3. Extramedullary disease (EMD) was reported in 40%. 35 patients (53,8%) were in first-line therapy.
The overall response rate with any triplet-based treatment containing always a proteasome inhibition and IMIds or alkylator was 49,2%, with 29,2% VGPR and 4,6% CR. The median PFS and OS were 6,9 and 14,9 months as a whole, respectively. The median PFS was greater when treatment combined bortezomib, lenalidomide and dexamethasone: 36,1 months ([0-99] vs 5,5 [0,59-10,4] otherwise; p=0,014). However, no difference in OS was demonstrated. Importantly, high dose therapy with ASCT was associated with longer PFS and OS, respectively 21,4 months ([12,8-30,1] vs 2,83 [0-5,7] p=0,003) and 50,4 months ([29,9-70,7] vs 6,27 [1,1-11,4] p=0,001). In multivariate analysis, poor OS was associated to acute renal failure at disease entry, presence of EMD, of del(17p), of hypercalcemia, and elevated lactate dehydrogenase.
We then sought to demonstrate that use of a direct anti proliferative-based agent such as anthracycline would participate to rapid disease reduction and PB clone control. It turns out that there was no significant difference in terms of survival in patients treated with an anthracycline-based regimen.
Conclusion
this study confirms the poor prognosis of PB feature in MM. A triple-based association with a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) seems to provide the best PFS in MM with PB, ideally complemented by ASCT. The role of anthracycline remains to be demonstrated. This data will be validated in a large cohort.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Treatment, Survival, Plasma cells, Multiple Myeloma
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