Prognostic Significance of Plasmablastic Plasma Cells in the Era of Novel Agents in Multiple Myeloma

Background:Plasmablastic (PB) feature has long been identified as poor prognosis in multiple myeloma (MM), although most data was reported in the era of conventional therapy. Furthermore, PB feature does not belong to the R-ISS scoring system in part due to lack of data since the emergence of novel therapy based regimens.

Methods: We have performeda retrospective multicenter analysisof all MMdiagnosed in the network area of the Poitiers academic hospital since 2005 to identify MM with PB features. PB was defined as presence of immature cells, any percentage, characterized with high proliferative index rate, centrally reviewed in Poitiers hematology laboratory by 3 hematologists.

Results: 65 MM with PB were identified, of which 53,8% were in first-line therapy. Adverse cytogenetic (IMWG) was reported in 6 patients, del17p x3, t(4;14) x2, and one with both. However, 33,8% were ISS 3, and 23,1% R-ISS 3. Presence of extramedullary disease (EMD) was reported in 40%. As a whole, ORR with any triplet-based treatment containing always a proteasome inhibitor 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, and independently of diagnosis or relapse settings. We noticed that one regimen appeared to fare much better than the other, namely VRd (bortezomib, lenalidomide and dexamethasone), with a median PFS at 36,1 months [CI95%: 0-99] vs 5,5 [0,59-10,4] otherwise; p=0,014. Similarly, ASCT was associated with longer PFS and OS, 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 respectively. We were not able to demonstrate that use of anthracyclines was able to control the PB clone, although it was one of our initial hypothesis. Univariate and multivariate analysis for poor OS identified acute renal failure at disease entry, presence of EMD, of del(17p), and high LDH, markers strongly associated to PB presence. We found that the % of PB correlated to poor prognosis on a linear fashion.

Conclusion: This study confirms the poor prognosis of PB feature in MM even in the era of novel agents. A triplet-based association PI + IMId + dex is warranted possibly consolidated by ASCT when possible. The role of the new anti CD38 monoclonal antibody has yet to be confirmed in this population.