Has the Prognostic of Primary Plasma Cell Leukemia Improved with New drugs?

Abstract Abstract 3869 Poster Board III-805 Introduction The outcome of patients with plasma-cell leukemia (PCL) is poor. Avet-Loiseau reported on behalf the IFM, our first experience in PCL patients and showed that the median overall survival (OS) was 8 months (Avet-Loiseau, Blood, 2001). Since 1999, novel agents such as Thalidomide, Bortezomib (Velcade) or Lenalidomide (Revlimid) have been widely used in the treatment of multiple myeloma, both at the time of relapse or part of upfront therapy. Patients and methods In this retrospective analysis, we have looked at the outcome of PCL patients treated within the IFM since 1999 in order to study the impact of novel agents on survival. Results 31 cases, 20 males, 11 females, median age 55 years (34-78) were analyzed. Twenty one patients less than 65 years received high-dose therapy as part of frontline treatment : 19 autologous haematopoietic stem cell transplantation (HSCT) and 5 allogeneic transplantation. Novel agents were used part of induction therapy in 6 cases, at the time of relapse for 9 patients, for both induction and relapse in 16 cases. Thirteen patients received 1 novel agent, 11 received 2 and 7 patients received the 3 novel agents. The median number of lines of therapy was 2 (1 to 4). Bortezomib was used as up front treatment in 15 patients and at relapse for 9 patients. Overall response rate according the IMWG criterias was 70% (17/24) including 11 CR or VGPR (45%). PAD (Bortezomib, Adriamycin and Dexamethasone) and VTD (Bortezomib, Thalidomide, Dexamethasone) regimens provided the best response rates. Lenalidomide was used in 13 patients mostly at relapse. A response was obtained in 53% of patients including 2CR and 2 VGPR (30%). Nineteen patients were treated with Thalidomide-based regimens. Overall response rate was 52% (10/19) including 2 CR and 6 VGPR (31%). Overall, for the whole group of patients, the median progression-free survival was 8 months (0-26) and the median OS was 15 months (6-108). When comparing this survival with that described in our previous experience reported before 1999, we clearly showed that the use of novel agents improved the survival of patients with PCL. Conclusion In this retrospective study, novel agents improved the prognosis of P-PCL. Prospective IFM phase II studies are ongoing to confirm these results. Disclosures: No relevant conflicts of interest to declare.

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Primary Plasma Cell Leukemia: Results of a Retrospective Italian Multicentric Survey.

Blood ◽

10.1182/blood.v114.22.2885.2885 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2885-2885

Author(s):

Livio Pagano ◽

Caterina Giovanna Valentini ◽

Valerio De Stefano ◽

Adriano Venditti ◽

Giuseppe Visani ◽

...

Keyword(s):

Plasma Cell ◽

Response Rate ◽

Conflicts Of Interest ◽

Alkylating Agents ◽

Plasma Cell Leukemia ◽

High Dose ◽

Cell Leukemia ◽

Front Line ◽

Line Therapy ◽

Primary Plasma Cell Leukemia

Abstract Abstract 2885 Poster Board II-861 Background: Epidemiological and clinical information on Primary Plasma Cell Leukemia (pPCL) are rarely reported. Aims: To evaluate in patients (pts) with pPCL the clinical features, the prognostic factors, and the efficacy of treatments. Patients and Methods: A multicenter retrospective cohort study was carried out between January 2000 and December 2008 in 26 Italian hematology divisions. A total of 128 cases of PCL were collected, and 73 of them (57%) were classified as primary (M/F 43/30). Results: The median age was 63 years (range 32-86). At diagnosis the median values of peripheral blood plasma cells and bone marrow plasma cell infiltration were 2.7 × 10 9/L (range 0.4-49.9) and 80% (range 37-100), respectively. The median values of hemoglobin, white blood cell count, and platelet counts were 9.1 g/dl (range 4.8-12.9), 13.7 × 10 9/L (range 1.3-56.7), 116 × 10 9/L (range 8-428), respectively. Extramedullary disease was present in ten cases (14%) and included testis, muscular, neuromeningeal, and cutaneous localization. At diagnosis, 64 pts (88%) had at least one CRAB sign, namely 35 pts (48%) had low hemoglobin level, 20 pts (27%) calcium ≥11 mg/dl, 32 pts (44%) creatinine ≥2 mg/dl, and 47 pts (64%) had osteolysis. In 41 pts (56%) cytogenetic study was performed, revealing an unfavourable karyotype in 17 (23%), in 13 of them del(13q-). Seventy-two pts received front-line therapy (1 died early, receiving only support treatments and steroids), that included antracycline-containing regimens in 36 pts (50%), and single alkylating agents in 17 pts (24%, 9 cyclofosfamide and 8 melphalan). In 11 of them Bortezomib (BTZ, n= 7) or Thalidomide (THAL, n= 4) were also employed. Finally, 19 pts (26%) received BTZ (4) or THAL (5) or both (10) as unique treatment. Twenty-one pts (29%) underwent autologous stem cell transplantation (SCT) as part of front-line therapy, followed by allogeneic-SCT in four cases; two additional pts underwent only allogeneic-SCT. A complete or partial remission after front-line therapy was achieved in 20 pts (27%) and 19 pts (26%) respectively (overall response rate 53%). The median overall survival (OS) was 13.1 months (range 0.5-75.8); 30.6 months (range 4.7-75.8) in responder pts and 4.2 months in non-responder ones (range 0.5-75.6, univariable hazard ratio, HR, 0.28, 95% CI 0.11-0.39). In the responder pts the median progression free survival (PFS) was 17.2 months (range 1.4-72.1). Of note, in SCT pts the median OS and PFS were 38.1 months (range 4.8-75.8) and 25.8 months (range 1.4-72.1) respectively, with a significant advantage with respect to non-transplanted pts in OS (median 9.1 months, range 0.5-75.6, HR 0.28, 95% CI 0.16-0.52) and in PFS (median 7.3 months, range 1.7-17.7, HR 0.29, 95% CI 0.04-0.44). The low number of allo-SCTs did not allow a reliable separate statistical analysis. A multivariable Cox proportional hazard regression analysis showed that OS was influenced by lack of initial response (HR 2.62, 95% CI 1.04-6.57), albumin <3 g/dl (HR 3.33, 95% CI 1.64-6.76), and SCT (HR 0.34, 95% CI 0.12-0.98). Pts with hypercalcemia at diagnosis had a shorter PFS (HR 4.0, 95% CI 1.04-15.24); the PFS was favourably influenced by SCT (HR 0.05, 95% CI 0.009-0.28). Overall, the use of BTZ and/or THAL did not influence the OS and PFS. Conclusions: pPCL is a highly aggressive lymphoprolipherative malignancy, characterized by a poor prognosis and a low response rate to conventional therapy. The use of high-dose chemotherapy followed by autologous or allogeneic-SCT is a very effective therapy leading to 66% increase in the OS and to 95% increase in PFS in respect to non-transplanted pts. Apparently, the use of novel drugs such as BTZ and THAL did not produce a further amelioration in the patient outcome. However, those latter findings should be taken with caution, given the relatively low number of treated pts. Disclosures: No relevant conflicts of interest to declare.

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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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Treatment with bortezomib-based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

American Journal of Hematology ◽

10.1002/ajh.23600 ◽

2013 ◽

Vol 89 (2) ◽

pp. 145-150 ◽

Cited By ~ 30

Author(s):

Eirini Katodritou ◽

Evangelos Terpos ◽

Charikleia Kelaidi ◽

Maria Kotsopoulou ◽

Sossana Delimpasi ◽

...

Keyword(s):

Plasma Cell ◽

Plasma Cell Leukemia ◽

Study Group ◽

Cell Leukemia ◽

Overall Response ◽

Secondary Plasma

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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

Blood Cancer Journal ◽

10.1038/s41408-018-0059-6 ◽

2018 ◽

Vol 8 (3) ◽

Cited By ~ 10

Author(s):

Eirini Katodritou ◽

Evangelos Terpos ◽

Sossana Delimpasi ◽

Maria Kotsopoulou ◽

Eurydiki Michalis ◽

...

Keyword(s):

Plasma Cell ◽

Real World ◽

Plasma Cell Leukemia ◽

Novel Agents ◽

National Study ◽

Study Group ◽

Cell Leukemia ◽

Real World Data ◽

World Data ◽

Primary Plasma Cell Leukemia

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C-MYC Rearrangement: A Marker for High-Risk Myeloma

Blood ◽

10.1182/blood.v120.21.4989.4989 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4989-4989

Author(s):

Isabella C. Glitza ◽

Gary Lu ◽

Su Chen ◽

Robert Z. Orlowski ◽

Muzaffar H. Qazilbash

Keyword(s):

Stem Cell ◽

Plasma Cell ◽

Response To Therapy ◽

Chromosome 8 ◽

Plasma Cell Leukemia ◽

Disease Stage ◽

High Dose ◽

Cell Leukemia ◽

Hematopoietic Stem ◽

Conventional Cytogenetics

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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Real World Data In Myeloma: Experiences From The Swedish Population-Based Registry On 2494 Myeloma Patients Diagnosed 2008-2011

Blood ◽

10.1182/blood.v122.21.1972.1972 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1972-1972 ◽

Cited By ~ 3

Author(s):

Cecilie Blimark ◽

Erik Holmberg ◽

Gunnar Juliusson ◽

Hareth Nahi ◽

Forsberg Karin ◽

...

Keyword(s):

Plasma Cell ◽

Real World ◽

Clinical Intervention ◽

Population Based ◽

Plasma Cell Leukemia ◽

Cell Leukemia ◽

First Report ◽

One Year ◽

The Impact

Abstract Introduction The Swedish Myeloma Registry (SMR) is a prospective observational registry designed to document real-world management and outcomes in newly diagnosed myeloma, with the purpose to improve the quality of the management of patients in Sweden. Population-based registries may provide complementary information on the management of patients to that of clinical intervention trials. With high representation and excellent data quality we can present valuable information in a whole population and reduce the impact of selection on outcome and reduce the subsequent problem with extrapolating data from clinical intervention studies on non-study populations. Methods The registry comprises web-reported data on all patients diagnosed with myeloma, plasmocytoma, and plasma cell leukemia from 2008 in Sweden, at time of diagnosis and after one year of follow-up. Coverage is analyzed through the compulsory Swedish Cancer Registry. Survival is achieved from the Swedish Tax Agency. Missing data are actively requested. This first report contains data on patients diagnosed between 2008 and 2011 with follow-up after one year on patients with symptomatic disease 2008-2010, with a follow-up through the end of 2012. Analyses of incidence, patient characteristics at baseline, proportion of patients given intensive treatment, obtaining very good partial remission (VGPR) and overall survival (OS) were estimated. Results Clinical data at baseline was available for 2494 patients (96% coverage)and 1- year follow-up data on 1427 patients (90% of all symptomatic cases initially reported), from 70 different centers in Sweden. The age adjusted incidence was 6.5 myeloma cases per 100 000 inhabitants and year. The median age was 70 years for men, and 73 years for women (34% younger than 66 years). At diagnosis, 76% were reported as symptomatic myeloma, 18% as smouldering myeloma, 5% plasmocytoma and 1% plasma cell leukemia. IgG-myeloma was most common (59%), followed by IgA (21%), Bence-Jones (13%), non-secretory (4%), IgD and IgM both less than 1%. Among symptomatic myeloma (n=1910), 76% had osteolytic lesions or compression fractures at diagnosis. Anemia (defined as hemoglobin levels below 10 g/dl) was seen in 33%, impaired kidney function (s-creatinin levels above 173 mmol/l) in 18%, and hypercalcemia in 21% at the time of diagnosis. In patients were ISS was available, 23%, 45% and 32% were in stage I, II, and III, respectively. Previous MGUS was known in 13 % of patients. Overall, 81 % of patients 65 years or younger received autologous stem cell transplantation (ASCT) and 4% of the elderly population. In the patients aged 65 years and younger, 63% of patients received one of the newer drugs in the first year of treatment, for the patients 66 to 80 years the number was 56%, and 25% of patients above 80 years. Throughout the study period, an increase in VGPR-rate on initial treatment was observed, more pronounced in younger patients (<66 years), from 35% in 2008 to 46% in 2010. For patients >65 years, the VGPR-rate increased from 17 to 27%. After a median of follow-up time of three years, OS was 63%. There was a significant difference in absolute and relative survival between younger and older patients. In symptomatic myeloma, patients 65 years or younger had an expected 3-year survival of 76% and in patients 66 years and above it was 50% (Figure). The relative 3-year survival for patients with asymptomatic patients was 81%. Discussion SMR is an instrument for increased quality in the management of plasma cell neoplasms in Sweden. This first report from the registry shows very high coverage and good adherence to guidelines in all regions of Sweden, both in diagnostics and treatment. A great effort is made to make the SMR complete and to present population-based data on management and outcome in Sweden. Longer follow-up is needed to address the question of the impact of new treatment options on the survival. The registry gives a great opportunity to perform population-based research of high quality based on the acceptance of the registry among treating physicians. Disclosures: Turesson: Celgene Corp: Honoraria.

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Conditional survival estimates for patients with plasma cell leukemia: An analysis of the SEER database.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e19533 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e19533-e19533

Author(s):

Veena Iyer ◽

Arindam Bagchi ◽

Danae Hamouda ◽

Qiang Nai ◽

Hosam Hakim ◽

...

Keyword(s):

Plasma Cell ◽

Metropolitan Areas ◽

Age Groups ◽

Geographic Location ◽

Plasma Cell Leukemia ◽

Novel Agents ◽

Cell Transplant ◽

Cell Leukemia ◽

Cancer Specific Survival ◽

Kaplan Meier

e19533 Background: Plasma cell leukemia (PCL) is an aggressive malignancy with poor prognosis. Retrospective studies have suggested improved outcomes with stem cell transplant and use of novel agents. Methods: We used the Surveillance, Epidemiology, and End Results database to identify 480 patients with PCL from 1973 to 2009. Kaplan Meier method was used to calculate 3-year Cancer Specific Survival (CSS) estimates, conditional on 1 to 3 years of survival (CS3). Covariates included age, sex, race and geographic location. The cohort was divided into three time frames, 1973-95, 1996-2005 and 2006-2009, to account for use of transplant from 1995 and novel agents from 2005. Results: 398 patients were selected for analysis from the initial cohort. Median age was 65. 50.75% were female and 65.8% were white. The 3-year CSS for patients with PCL was 19.6% and conditional probability of surviving additional 3 years (CS3) at 1, 2, 3 and 5 years from diagnosis was 36.9%, 51.5%, 58.5% and 71.2% respectively. CSS rates at 3 years during 1973-95, 1995-2005 and 2006-2009 were 14.7%, 12.4% and 32.9% respectively and the CS3 improved from 37.4% / 27.9% / 44.5% at 1 year to 72.7% / 46.3% / 57.5% at 3 years. 3-year CSS rates of patients aged < 50, 50-59, > 70 years was 19.9%, 19.7% and 18.7% respectively. The CS3 with each year survived increased for all age groups, with the most dramatic increase for those > 70 years (45.8% at 1 year to 80.5% at 3 years). Hispanics had the lowest 3-year CSS rate (5.5%). Improvement in CS3 from 1 to 3 years for races was as follows – Whites: 35.8% to 57.9%, Blacks: 41.9% to 50.10%, Asians: 28.6% to 67% and Hispanics: 18.7% to 33.3%. 3-year CSS rate for patients from metropolitan/non-metropolitan areas was 19.5%/18%. CS3 for metropolitan/non-metropolitan areas increased from 38.2%/27.3% at 1 year to 63%/33.3% at 3 years. Conclusions: The risk profile of patients with PCL changes as they survive past the diagnosis. Improvements in survival are more substantial in older patients and patients from metropolitan areas.

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