Therapeutic Advances in the Treatment of Primary Plasma Cell Leukemia: A Focus on Hematopoietic Cell Transplantation

Abstract

Primary plasma cell leukemia (pPCL) is an uncommon but aggressive plasma cell malignancy associated with frequent extramedullary involvement, high-risk cytogenetic abnormalities, and frequent organ dysfunction, ultimately resulting in poor prognosis. Here we review recent advances in our understanding of the molecular and biological aspects of PCL and summarize therapeutic progress occurring over the past 2 decades. pPCL is distinguished from secondary PCL arising from multiple myeloma. The molecular and immunophenotypic changes of pPCL are often distinct from those seen in secondary PCL and multiple myeloma. The availability of novel agents (ie, proteasome inhibitors and immunomodulatory agents) and the increasing use of hematopoietic cell transplantation strategies have resulted in better outcomes, although long-term survival remains poor. Development of complex treatment algorithms that combine novel agents as induction therapy, as part of conditioning regimens for hematopoietic cell transplantation (autologous or allogeneic), or as post-transplantation remission strategies are logical and may translate into improved survival in patients with PCL.

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

“…To our knowledge, novel agents and auto-HSCT as consolidation after induction therapy are useful for the treatment of pPCL patients as well as in improving their outcome [13,15,16,17,18,19,20,21]. 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.…”

Melphalan/Total Body Irradiation–Conditioned Myeloablative Allogeneic Hematopoietic Cell Transplantation for Patients With Primary Plasma Cell Leukemia

“…2 Poor outcomes seen in some of these patients may have resulted from unfavorable patient-or disease-related characteristics, or both, and it would seem appropriate to offer this intensive therapy only to selected patients, such as those of younger age with adequate performance status and organ function, lack of significant comorbidities, minimal or no disease at the time of alloHCT, and a wellmatched donor. It should be noted that the optimal conditioning and post-alloHCT maintenance regimens as well as GVHD prophylaxis for these patients is unknown, and poor historical outcomes may also have resulted from specific therapy-related toxicities.…”

“…1 However, more effective disease control has been achieved with the use of novel agentecontaining regimens, 2 and an overall response rate of nearly 80% has been reported in patients with pPCL receiving bortezomib-based therapies. 3 Similar to patients with multiple myeloma (MM), those with pPCL are frequently offered consolidation with high-dose melphalan followed by autologous stem cell transplantation (ASCT).…”

“…4 Smaller retrospective series show similar or less favorable survival outcomes for patients with pPCL undergoing ASCT. 2,5 Allogeneic hematopoietic cell transplantation (alloHCT) has also been incorporated into the management of patients with pPCL. An analysis of 50 patients undergoing alloHCT reported by the Center for International Blood and Marrow Transplant Research (CIBMTR) demonstrated a 3-year PFS rate of 20% and a 3-year OS rate of 38%, along with a 3-year nonrelapse mortality rate of 41%.…”

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

“…The results of the 2 largest retrospective series of PPCL patients treated with ASCT have also been recently reviewed [9]. Overall, ASCT was able to induce a higher rate of complete response, but appeared to be less effective than in MM in the long term, due to the short duration of posttransplant response and increased non-relapse-related mortality.…”