Plasma cell leukemia: Detailed studies and response to therapy

Abstract Abstract 4989 Background: The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth, and apoptosis. c-MYC is mapped to the 8q24. 1 on the long arm of chromosome 8 and its rearrangement has been reported in 15% of myeloma patients independent of the disease stage (Avet-Loiseau et al. Blood 2001). However, the clinical significance of c-MYC rearrangement is not well described. Here we report the characteristics and outcome of myeloma patients with c-MYC rearrangements that were treated at our institution. Methods: We identified 18 patients (11 males, 7 females) with c-MYCrearrangements either on fluorescence in situ hybridization (FISH) analyses or conventional cytogenetics, who were treated at the M.D. Anderson Cancer Center. The primary objective was to describe the patient characteristics, response to therapy, time to progression (TTP), and overall survival (OS). Results: Median age at diagnosis was 56. 5 years (21–72). Overall, 8 patients (44%) presented with or progressed to either plasma cell leukemia (PCL: 6) or plasmablastic myeloma (PBM: 2). Abnormalities involving chromosome 8q24. 1, the c-MYC locus, were detected on conventional cytogenetics in all 18 patients, including t(8;14)(q24. 1;q32) in 6 cases, t(2;8)(p12;q24. 1) in 3 cases, t(8;22) (q24. 1;q11. 2) in 4 cases, t(8;20)(q24. 1;q13. 3) in one case, and an abnormal chromosome 8 with unknown material attached to the 8q24. 1 region in 4 cases. Five patients (27%) had a del(13)(q14. 1)/RB1, one of whom had a del(17)(p13)/TP53, while 3 other patients had t(11;14)(q13;q32) involving CCND1-XT/IGHrearrangements. Twelve patents (66%) received induction with a novel agent: bortezomib-based = 8 (44%) and thalidomide- based = 4 (22%). Six patients (33%) received induction with conventional chemotherapy regimens: CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) = 2, pulsed steroids only = 2, EPOCH (Etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) = 1 and melphalan + prednisone =1. Nine patients achieved a partial response (PR, 50%) and 4 patients achieved a very good partial remission (VGPR, 22%), with an overall response rate of 72% to induction. Thirteen patients (72%) went on to receive high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). Four patients died of disease progression before auto-HCT while one patient opted for stem cell harvest and cryopreservation only. Median time to auto-HCT was 7. 1 months (3. 6–12. 7). Median follow up in all patients was 13 months (range 3. 4–105). Fifteen patients had progressed, with a median TTP of 7. 1 months and a median OS of 20. 2 months. Patients with PCL or PBM had significantly shorter OS (p=0. 04). Conclusion: This is the first report describing clinical characteristics of myeloma patients with c-MYC rearrangements. c-MYC rearrangement is associated with a higher incidence of plasma cell leukemia or plasmablastic myeloma, short TTP and OS. Disclosures: No relevant conflicts of interest to declare.

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Plasma cell leukemia: An evaluation of response to therapy

The American Journal of Medicine ◽

10.1016/0002-9343(87)90942-9 ◽

1987 ◽

Vol 83 (6) ◽

pp. 1062-1068 ◽

Cited By ~ 103

Author(s):

Pierre Noel ◽

Robert A. Kyle

Keyword(s):

Plasma Cell ◽

Response To Therapy ◽

Plasma Cell Leukemia ◽

Cell Leukemia

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A successful case of venetoclax-based therapy in relapsed/refractory secondary plasma cell leukemia

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219895072 ◽

2019 ◽

Vol 26 (5) ◽

pp. 1274-1278

Author(s):

Allison Kupsh ◽

Justin Arnall ◽

Peter Voorhees

Keyword(s):

Partial Response ◽

Plasma Cell ◽

Response To Therapy ◽

Plasma Cell Leukemia ◽

Cell Leukemia ◽

Successful Case ◽

Pet Ct ◽

Drug Regimens ◽

Secondary Plasma ◽

Good Partial Response

Background Secondary plasma cell leukemia (sPCL) patients typically are either refractory to conventional therapies or have short remissions to drug regimens used in multiple myeloma (MM), which highlights sPCL’s aggressive nature and association with advanced stage disease. t(11,14) is correlated with increased BCL-2 expression, which makes it a cytogenic marker of interest for use of the BCL-2 inhibitor venetoclax. Little data of venetoclax’s use has been published in plasma cell leukemia. We present a case of a refractory/relapsed sPCL patient displaying t(11,14) who achieved a very good partial response (VGPR) from venetoclax therapy in combination with dexamethasone and bortezomib. Case report Our case describes a 67-year-old male initially diagnosed with IgG kappa MM in 2013, which transformed into non-secretory secondary plasma cell leukemia. Over a two-year period, despite responses to various therapies, the patient continued to experience relapses and exhausted options of novel agents seen in MM treatment. The patient was started on venetoclax in combination with bortezomib and oral dexamethasone. Management and outcome Due to the patient’s disease transformation into a non-secretory form of sPCL, PET/CT scans were relied upon to monitor disease progression. The PET/CT scan after three months of venetoclax combination treatment showed a very good partial response to therapy, with near resolution of metabolically active osseous disease. Discussion The success of venetoclax-based therapy in achieving a very good partial response suggests its utility in relapsed/refractory sPCL patients, who have exhausted various combinations of drug regimens used in treatment of MM and have historically poor survival outcomes.

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Cytogenetics and Clinical Outcomes of Plasma Cell Leukemia Patients: A Single Institution Experience.

Blood ◽

10.1182/blood.v114.22.4932.4932 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4932-4932

Author(s):

Daniel J. Lebovic ◽

Rachid Baz ◽

Melissa Alsina ◽

Jose L Ochoa ◽

Daniel Sullivan ◽

...

Keyword(s):

Overall Survival ◽

Plasma Cell ◽

Plasma Cells ◽

Response To Therapy ◽

Plasma Cell Leukemia ◽

Novel Agents ◽

Cell Leukemia ◽

Allogeneic Transplant ◽

The Impact

Abstract Abstract 4932 Introduction Plasma cell leukemia (PCL) is a rare, poorly understood and clinically aggressive plasma cell dyscrasia that can originate from multiple myeloma (sPCL) or de novo as primary PCL (pPCL). Historically, median survival of patients with PCL has been reported to be 1 and 11 months for patients with secondary and primary PCL, respectively (Tiedemann, Leukemia 2008). The impact of novel agents and transplantation strategies on outcomes of patients with PCL remains unclear. In addition, few have reported extensively on the cytogenetics abnormalities seen in patients with PCL especially with respect to outcomes with novel therapies (proteasome inhibitor or immunomodulator). Accordingly, we thought to evaluate the clinical, cytogenetic features and outcomes of patients with PCL treated at H. Lee Moffitt Cancer Center in the era of novel agents and transplant strategies. Materials and Methods Retrospective review of records of patients with PCL diagnosed after 2003. The diagnosis of PCL was according to the IMWG criteria (specifically peripheral blood plasma cells ≥ 20% or 2 ×109/L). Clinical data reviewed included basic demographic, laboratory, pathologic, treatment and outcomes variables. Cytogenetics was reviewed by metaphases and FISH. Overall survival was defined as the time from diagnosis of PCL to death or last follow-up. Response criteria was according to the IMWG. Treatment was at the discretion of the treating physician. Results Twenty four patients with PCL were identified: 15 patients had pPCL and 9 had sPCL. The median age of all patients was 58 years (range 37-77years). The median peripheral WBC was 15×109/L (range 3-102 ×109/L) and the median percent of peripheral plasma cells was 40% (15-93%). The median β2 microglobulin was 3 mg/L (range 1.4-23). Nine patients (38%) had renal failure (creatinine>2.0mg/L) at diagnosis of PCL and 11/19 (58%) had a serum LDH greater than the institution's upper limit of normal. Two patients had CNS disease and 6 patients had extramedullary disease. Regarding metaphase cytogenetics: One patient had a novel translocation involving 3 separate breakpoints, which included: ins(6;14)(p22;q32q32)t(6;11)(p22;q13), der (14) ins (11)(q32;q13q13)?? t(6;14)(p22;q32), 3 patients (2 with pPCL) had a translocation between chromosomes 1 and 16 including t(1;16)(q21;q24), t(1;16)(q21;22) and t(1;16)(break points not reported). 14/23 patients with PCL (61%) had deletion of chromosome 13 by either FISH or cytogenetics; while 80% of patients with pPCL (12/15) had 13q deletion. Only one patient had deletion 17p. 11 patients received bortezomib based therapy and 19 patients received a novel agent, 5 had an allogeneic transplant, 19 had high dose therapy and autologous transplantation). Best response to therapy was as follows: 9 CR, 4 VGPR, 4PR, 1MR, 2 Non evaluable (PR and better: 77%). After a median follow up of 13 months, 5 remain alive (all had autologous transplant and 3 had an allogeneic transplant) (median follow up 2 years; range 2-34 months). The median overall survival for pPCL compared to sPCL via Kaplan-Meier was 28.4 vs. 3.5 months, respectively (p=0.0018). See Figure 1. Conclusion We herein report novel cytogenetic abnormalities in patients with PCL (1 unique translocation involving chromosomes 6, 11 and 14 as well as 3 patients with t(1; 16) which has rarely been reported). Despite generally poor outcomes with traditional therapies, patients treated with novel agents and allogeneic transplant may enjoy a longer survival than previously reported. Disclosures Off Label Use: Lenalidomide in newly diagnosed myeloma. Baz:celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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