Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome

2016 ◽  
Vol 34 (18) ◽  
pp. 2125-2132 ◽  
Author(s):  
Bruno Royer ◽  
Stéphane Minvielle ◽  
Momar Diouf ◽  
Murielle Roussel ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Phase Ii ◽  
Cell Leukemia ◽  
Reduced Intensity Conditioning ◽  
Prospective Phase ◽  
Primary Plasma Cell Leukemia ◽  
Reduced Intensity

Purpose Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. Patients and Methods Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). Results Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). Conclusion In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.

A Pilot Study of Reduced-Intensity Conditioning Stem Cell Transplantation with T-Cell Replete HLA-Mismatched Allograft from Child to Parent Patient for the Treatment of Refractory Adult T-Cell Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5406-5406
Author(s):  
Hiroshi Fujiwara ◽  
Atsuo Ozaki ◽  
Makoto Yoshimitsu ◽  
Heiichiro Hamada ◽  
Hideaki Kawada ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Pilot Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Cell Leukemia ◽  
Reduced Intensity Conditioning ◽  
Adult T Cell Leukemia ◽  
Reduced Intensity

Abstract [Background/Purpose] Adult T-cell leukemia (ATL) is a most aggressive lymphoid malignancy with poor prognosis, and at present, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been an only curative modality. Nevertheless, not only the aggressive nature of disease itself, but also the aging of patients older than 55 y.o. contribute to therapeutic impediments by comorbidity and difficulty of timely acquiring HLA-matched sibling donor. In this setting, allograft from child to parent patient is a realistic modality. We report a result of a prospective study evaluating the efficacy of reduced -intensity conditioning SCT (RIST) with HLA-mismatched allograft from child to parent for ATL patients. [Patients/methods] 5 patients (2 males, and 3 females) with ATL in progressive disease (PD) after induction chemotherapy with LSG15 regimen who had no HLA-identical sibling donors were enrolled. Patient median age was 59 y.o. All donors were sons with haploidentical HLA. Median age of donor was 29 y.o. KIR ligands were matched. Preparatory regimen consisted of fludarabine (180mg/m2), busulfan (8mg/m2) or cyclophosphamide (120mg/kg) and rabbit antithymocyte globulin (2.5mg or 5.0mg/kg). Stem cell source was G-CSF mobilized PBSC. Mean infused CD34 cell number was 8.3×106/kg (from 4.1 to 23.3 × 106/kg). GVHD prophylaxis consisted of tacrolimus or cyclosporine and short term methotraxate and mycophenolate mofetil. [Results] Median interval from induction chemotherapy to transplantation was 5 months. Median observation interval was 8 mo. (from 3.5 mo. to 31 mo.). All 5 cases had neutrophil engraftment at day 15 after transplantation. In 5 of 5 cases, complete donor T-cell chimerism were obtained by day 30. Overall survival (OS) and progression free survival (PFS) at 1 year was 50%, and 26.7%, respectively. Evaluation of peripheral residual disease demonstrated by HTLV-I proviral load and soluble interleukin-2 receptor (sIL-2R) value documented the strong disease suppression by this transplants. Analysis of NK cell kinetics revealed that donor-derived NK cells expanded and exerted killing activity mainly until 4 months after transplantation, and decreased in number thereafter. These findings indicated all achieved complete donor T-cell chimerism followed by clinical observations for graft vs. ATL effect. Although, disease progression occurred 4 of 5 cases, 2 achieved remission again with the longest response duration of 31 mo. All but UPN2 experienced GVHD (grade 2 to 4), and UPN2 had early relapse and died of ATL at 4 mo. after allo-HSCT. Frequent reactivations of cytomegalovirus were observed, but well controlled by ganciclovir. [Summary] In our pilot study, RIST with T-cell replete HLA-mismatched allograft from child to parent patient could provide timely donor acquisition and durable remission for all patients with refractory ATL. This setting may be one of realistic modalities for ATL patients who need alternative donors.

scholarly journals Primary plasma cell leukemia and autologous stem cell transplantation

Haematologica ◽  
2010 ◽  
Vol 95 (5) ◽  
pp. 804-809 ◽  
Author(s):  
M. B. Drake ◽  
S. Iacobelli ◽  
A. van Biezen ◽  
C. Morris ◽  
J. F. Apperley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cell ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
Primary Plasma Cell Leukemia

First Large Prospective Study For Patients With Primary Plasma Cell Leukemia: Bortezomib-Doxorubicine-Dexamethasone/Bortezomib-Cyclophosphamide-Dexamethasone Regimens As Induction Before Stem Cell Transplantation Followed By Consolidation With Lenalidomide-Bortezomib-Dex Or Allograft. (a study of the IFM group)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 761-761
Author(s):  
Bruno Royer ◽  
Florence Magrangeas ◽  
Bruno Lioure ◽  
Jean-Paul Fermand ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Prospective Study ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Plasma Cells ◽  
High Dose ◽  
Cell Leukemia ◽  
Primary Plasma Cell Leukemia

Abstract Introduction Primary plasma cell leukemia (pPCL) is a rare form of plasma cell malignancy with poor prognosis (usually less than 12 months survival with conventional chemotherapy). Only one prospective study with Lenalidomide-Dex before high dose therapy has been recently reported1. Bortezomib-based regimens and high dose Melphalan/ autologous stem cell transplantation (HDM/ASCT) have shown promising results in small retrospective studies. We report here the first prospective multicenter phase II trial for pPCL patients (pts) treated with Bortezomib-Doxorubicine-Dexamethasone (PAD) / Bortezomib-Cyclosphosphamide-Dexamethasone (VCD) as induction before HDM/ASCT. With the aim to improve response and survival, allograft or second ASCT plus consolidation/maintenance with Lenalidomide-Bortezomib-Dex (VRD) were proposed. Patients and method Non-previously treated pts with a diagnosis of pPCL were enrolled in this phase II study of the IFM group from April 2010 to July 2013. PAD (dexa 40 mg + bortezomib 1,3 mg/m2 on day 1, 4, 8, 11 + doxorubicine 30 mg/m2 day 4) and VCD (dexa + bortezomib + cyclophosphamide 300 mg/m2 day 1, 8) were administrated alternatively each 21 days for 4 cycles. For responding patients with circulating plasma cell < 1%, peripheral stem cells were collected after Cyclophosphamide + G-CSF. Either (i) double HDM/ASCT was performed followed by consolidation/maintenance íVDR (dexa 40mg + bortezomib 1,3 mg/m2 on day 1, 4, 8, 11 + lenalidomide 15 mg day 1-15) each 3 months and Lenalidomide 15 mg 21/28 days on others months, for 1 yearý or (ii) tandem HDM/ASCT-reduced intensity conditioning-allograft if there were < 66 years-old. Primary end-point was progression free survival (PFS); secondary end-points were responses rates, overall survival (OS), feasibility, and toxicity. We evaluated the disease response to therapy with the IMWG criteria and the percentage of circulating plasma cells; minimal residual disease (MRD) was evaluated during follow-up. Peripheral circulating plasma cells and bone marrow plasmocytes were collected at diagnosis for centralized FISH and SNP array analysis. Results 40 pts were enrolled with a median age of 55y (27-71). Median follow-up was 12.6 months (7.6-24.8). At diagnosis, the median number of circulating plasma cell was 5.2 G/L (1.3-66). Twenty-two percent had creatinine clearance < 50 ml/min, and 11% < 30 ml/min, 44% had an ISS score of 2 and 37% ISS 3. After induction 35 pts are evaluable. In the intent to treat analysis, 25 (72%) responded (VGPR+CR 37%, PR 28%, SD 5%) and 10/35 (28%) were refractory (pts having circulating plasma cell ≥ 1%) and did not continue the study. Twenty-three of the 25 responding pts underwent HDM/auto and 20 pts are evaluable at 3 months: CR+VGPR 14/20 (70%), PR 4/20 (20%), 1/20 (5%) and PD 1/20 (5%). Second HDM/auto was performed in 6 pts and allograft in 12. Ten of the 14 (72%) evaluable pts achieved VGPR or better and 4/14 (28%) PR. Six pts are currently on consolidation/maintenance phase with VRD. Median PFS was 17.8 months. Median OS was not reached. Genomic data are shown in Table I. MDR evaluation will be presented later. Major toxicities were hematological and infections. Eight pts died: 5 during induction, 1 at HDM/ASCT and 2 post allograft while in relapse. Of note, 2 pts had meningeal involvement at relapse. Conclusion This first large study for pPCL patients with PAD/VCD as induction and HDM/ASCT is effective and induce high responses rates. Consolidation with Allograft or bortezomib-lenalidomide-dex is currently investigated. 1Musto P et al. Blood (ASH Annual Meeting Abstracts) 2011; 118 Abstract2925Table I: genomic Disclosures: Leleu: CELGENE: Honoraria; JANSSEN: Honoraria. Moreau:Celgene: Honoraria, Speakers Bureau. Avet-Loiseau:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

scholarly journals The Outcomes of Korean Patients with Primary Plasma Cell Leukemia: Analysis of Korean Multiple Myeloma Working Party (KMM160)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4445-4445
Author(s):  
Sung-Hoon Jung ◽  
Je-Jung Lee ◽  
Kihyun Kim ◽  
Dok Hyun Yoon ◽  
Chang-Ki Min ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Young Patients ◽  
Complete Response ◽  
Novel Agents ◽  
Survival Outcomes ◽  
Cell Leukemia ◽  
Primary Plasma Cell Leukemia

Abstract Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapid clinical course. In this study, we evaluated the treatment status and survival outcomes of Korean patients with pPCL. Seventy patients were diagnosed with pPCL between February 1998 and December 2015. The median age of the patients was 63.5 years (range, 34-85). Most of patients (70.0%) had International Staging System III.Conventional karyotyping was assessed in 47 patients and FISH analysis was performed in 43 patients. Abnormal karyotype was detected in 34 patients (72.3%). The most common abnormalities were complex karyotype (65.9%). Hypodiploidy, del (13q14), del (17p13), and t(11;14) were found16 (34%), 14 (29%), 12 (25%), and 11 (23%) patients, respectively. Amongthe 70 patients, 60 patients were treated.Thirty-six patients were initially treated with novel agents and 12 received novel-containing regimens as salvage therapy. Twelve patients received conventional chemotherapies only. Twenty-two patients underwent high dose chemotherapy and autologous stem cell transplantation (HDT/ASCT), and one received the allogeneic stem cell transplantation. After a median follow-up of 16.5 months, overall survival (OS) was 16.1 months (95% CI, 11.7-20.8). Twenty patients (33.3%) died within less than one year following the diagnosis, and the early mortality rate was lower in patients who were initially treated with novel agents (22.2% vs. 50.0%, p = 0.049). The median OS of three treatment groups comprising conventional chemotherapy only, novel agents only, and novel agents + HDT/ASCT were 2.9, 12.3, and 31.1 months, respectively (P=0.001). Patients who achieved complete response (CR)after initial therapy had significantly improved OS than did others (36.4 vs. 14.1 months, P < 0.011). On multivariate analysis, achievement of complete response (CR) after induction therapy (HR 0.066, 95% CI 0.007-0.615, P = 0.017), increased lactate dehydrogenase (HR 4.803, 95% CI 1.202-19.186, P = 0.026), andserum beta2-microglobulin > 5.5 mg/dl (HR 3.218, 95% CI 1.011-10.238, P = 0.048)were significantly associated with survival outcomes. In young patients (age < 65 years), performance of HDT/ASCT (HR 0.038, 95% CI 0.004-0.381, P = 0.005) was significantly associated with improved OS. In conclusion, patients with pPCL had poor survival outcomes, and achieving CR after induction therapy associated with increased OS. In addition, performance of HDT/ASCT is important treatment modality to improve OS in young patients with pPCL. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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