Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: a multicenter national study by the Greek Myeloma Study Group

Abstract

We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 18 months respectively, both significantly longer in patients treated with bortezomib-based therapy + ASCT vs. others (PFS: 18 vs. 9 months; p = 0.004, OS: 48 vs. 14 months; p = 0.007). Bortezomib-based therapy + ASCT predicted for OS in univariate analysis. In multivariate analysis, achievement of ≥vgPR and LDH ≥ 300 U/L were significant predictors for OS. These real-world data, based on one of the largest reported national multicenter series of pPCL patients treated mostly with novel agents support that, among the currently approved induction therapies, bortezomib-based regimens are highly effective and reduce the rate of early mortality whereas in combination with ASCT consolidation they prolong OS.

Survival outcomes of patients with primary plasma cell leukemia (pPCL) treated with novel agents

“…We confirmed that the greatest survival benefit, in terms of both PFS (25 vs 6 months) and OS (36 vs 26 months), was observed among the patients who underwent ASCT, thus validating the role of ASCT as a standard consolidation approach after initial cytoreduction, as previously described . In this light, the promising 6‐month OS (92%) observed in the overall population supports the benefit of combining bortezomib with IMiDs upfront to obtain rapid disease control and enable transplantation‐eligible patients to proceed to ASCT.…”

“…In the current study, both the median PFS (20 months) and the median OS (33 months) for the entire population compared favorably with those reported using lenalidomide‐based (15 and 28 months, respectively) and bortezomib‐based (12 and 18 months, respectively) regimens …”

“…In the current study, both the median PFS (20 months) and the median OS (33 months) for the entire population compared favorably with those reported using lenalidomide-based (15 and 28 months, respectively) and bortezomib-based (12 and 18 months, respectively) regimens. 13,23 Although cross-trial comparisons are difficult to perform, in our study, combining bortezomib and IMiDs appeared to improve the ORR (82% vs 69%) and the CR rate (44% vs 33%) obtained after the induction phase, reducing the rate of patients who had primary refractory disease (5% vs 26%,) compared with the bortezomib-based induction regimen adopted in the IFM trial. This, along with a longer duration of maintenance (3 years vs 1 year), might account for the better PFS observed in our trial.…”

“…In a phase 2 trial presented by the Intergroup Francophone du Myelome (IFM), ASCT‐eligible patients with pPCL received a bortezomib‐based induction regimen followed by tandem SCT; combined bortezomib, lenalidomide, and dexamethasone (VRD) consolidation; and lenalidomide maintenance. This approach resulted in a median OS of 36 months …”

“…This approach resulted in a median OS of 36 months. 12,13 Despite the impressive improvement in survival outcomes among all patients with MM, especially with the increasing use of SCT and the incorporation of novel agents into the induction and maintenance phases, 14 the survival improvement observed in patients with pPCL still is not on a par with that attained in patients with MM. 15 Here, we present a single-center, retrospective analysis of patients with pPCL with the objective of validating the role of ASCT and the incorporation of PIs and IMiDs into the induction and maintenance phases.…”