Regular Follow-Up of MGUS Allow Early Detection of Malignant Transformation Before Severe Complications Occur.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4774-4774
Author(s):  
Olivier Decaux ◽  
Sophie Besnard ◽  
Antoinette Perlat ◽  
Claire Cazalets ◽  
Berengere Cador ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Detection ◽  
Serum Creatinine ◽  
Malignant Transformation ◽  
De Novo ◽  
Severe Complication ◽  
University Hospital ◽  
Medical File ◽  
Hematopoietic Stem

Abstract Background: Monoclonal gammapathy of unknown significance (MGUS) is a frequent disorder that carries a 1% per year risk of progression to multiple myeloma (MM). Patients should be monitored annually to detect malignant transformation before complications occur. Objective: To assess if MGUS regular follow-up allow early detection of malignant transformation before severe complications occur. Progression to multiple myeloma was established according to the criteria defined by the International Working Group. Criteria for severe complication were: hypercalcemia (> 3 mmol/l), acute renal insufficiency needing dialysis, bone fracture, sepsis. Methods: We retrospectively reviewed medical data of patients treated for post-MGUS multiple myeloma in Internal Medicine Departement of Rennes University Hospital (France) between 1980 and 2006. Results: Forty two patients were identified (23 men and 19 women). Median age was 66 years old (49 – 79) at the time of MGUS diagnosis and 70,5 years old (51 – 84) at the time of MM diagnosis. Isotype was: IgG in 37 patients (88%), IgA in 2 (5%) and biclonal IgG/IgA in 3 (7%). Median level of monoclonal component was 19,9 g/L (4,9 – 42,2) at MGUS diagnosis and 35,3 g/L (15,2 – 68) at the time of MM diagnosis. Median bone marrow plasmocytosis was 4% (0–10) for MGUS and 12% (1–30) for MM. Median time from MGUS diagnosis to malignant transformation was 4 years (1 – 12). Anemia (hemoglobin concentration ≤12 g/dL) was present at the time of MM diagnosis in 16 (38%) patients. It was generally moderate in severity; only 6 (14,2%) patients had a hemoglobin value of 10 g/dL or less and no patients had a haemoglobin value of 8 g/dL or less. The serum creatinine level was increased (more than 100 μmol/L) in 6 (14,2%) patients and no patients had a serum creatinine value of 200 μmol/L or more at the time of MM diagnosis. Two patients had an hypercalcemia (2,60 mmol/L or more) at the time of MM diagnosis. In 30 patients (71%), malignant transformation was detected before a severe complication occurs. In 8 patients (19%) a severe complication occurred before multiple myeloma diagnosis: hypercalcemia (2 cases), sepsis (2 cases), spinal fracture with epiduritis (3 cases), spontaneous sternum fracture (1 case). Four of these patients had refused follow-up and were not monitored for MGUS evolution despite medical explanations as regards to the risk of malignant transformation. In 4 patients (10%) criteria of MM diagnosis were not found in medical file because diagnosis was made in another hospital.) Most patients were treated with conventional chemotherapy (40% with MP) and two with autologous hematopoietic stem cell transplantation. The median survival after malignant transformation was 48 months. Conclusions: Regular follow up of patients with MGUS allows earlier diagnostis of MM and prevent them for severe complications. We plan to compare this group with patients treated in our department for de novo MM during the same period of time.

scholarly journals Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 2906-2912 ◽  
Author(s):  
D Haase ◽  
M Feuring-Buske ◽  
S Konemann ◽  
C Fonatsch ◽  
C Troff ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Hematopoietic Stem Cells ◽  
Malignant Transformation ◽  
Cell Sorting ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a heterogenous disease according to morphology, immunophenotype, and genetics. The retained capacity of differentiation is the basis for the phenotypic classification of the bulk population of leukemic blasts and the identification of distinct subpopulations. Within the hierarchy of hematopoietic development and differentiation it is still unknown at which stage the malignant transformation occurs. It was our aim to analyze the potential involvement of cells with the immunophenotype of pluripotent stem cells in the leukemic process by the use of cytogenetic and cell sorting techniques. Cytogenetic analyses of bone marrow aspirates were performed in 13 patients with AML (11 de novo and 2 secondary) and showed karyotype abnormalities in 10 cases [2q+, +4, 6p, t(6:9), 7, +8 in 1 patient each and inv(16) in 4 patients each]. Aliquots of the samples were fractionated by fluorescence-activated cell sorting of CD34+ cells. Two subpopulations, CD34+/CD38-(early hematopoietic stem cells) and CD34+/CD38+ (more mature progenitor cells), were screened for karyotype aberations as a marker for leukemic cells. Clonal abnormalities and evaluable metaphases were found in 8 highly purified CD34+/CD38-populations and in 9 of the CD34+/CD38-specimens, respectively. In the majority of cases (CD34+/CD38-, 6 of 8 informative samples; CD34+/CD38+, 5 of 9 informative samples), the highly purified CD34+ specimens also contained cytogenetically normal cells. Secondary, progression-associated chromosomal changes (+8, 12) were identified in the CD34+/CD38-cells of 2 patients. We conclude that clonal karyotypic abnormalities are frequently found in the stem cell-like (CD34+/CD38-) and more mature (CD34+/CD38+) populations of patients with AML, irrespective of the phenotype of the bulk population of leukemic blasts and of the primary or secondary character of the leukemia. Our data suggest that, in AML, malignant transformation as well as disease progression may occur at the level of CD34+/CD38-cells with multilineage potential.

scholarly journals Successful treatment of gastric relapse in multiple myeloma with bortezomib after autologous hematopoietic stem cell transplantation (autoHSCT)

2013 ◽  
Vol 5 (1) ◽  
pp. e2013006
Author(s):  
Serdar Sivgin
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Plasma Cells ◽  
University Hospital ◽  
Hematopoietic Stem ◽  
Relapsed Disease

We report a  case of  59-year-old Turkish   man with history of MVR and COPD whom was diagnosed with stage IIIA IgG lambda multiple myeloma (MM) in 1997. He underwent autologous hematopoietic stem cell transplantation following melphalan 200mg per body area(m2)in February 2006. On 18th of February 2011; he was admitted to the emergency service of university hospital with complaints of hematemesis and melena. In gastric biopsy obtained from the lesion; pathological evaluation showed monoclonal lambda light chain infiltration originated from neoplastic plasma cells in gastric mucosa. The patient was considered as local gastric relapsed disease and was treated with 2 cycles of bortezomib. An excellent response was achieved after  2 cycles of BEP regimen, his paraprotein levels dropped below 10 g/L and there was no recurrence of the hematemesis or melena.

Durable Remission with Salvage Autotransplants in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1227-1227
Author(s):  
Nina Shah ◽  
Khawaja Fraz Ahmed ◽  
Sofia Qureshi ◽  
Jatin Shah ◽  
Robert Z Orlowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Time ◽  
Chromosomal Abnormalities ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Remission Duration

Abstract Abstract 1227 Poster Board I-249 Background In comparison with single autologous hematopoietic stem cell transplantation (auto HCT), tandem autologous HCT has resulted in longer event-free and overall survival in randomized trials for patients with newly diagnosed multiple myeloma (MM). Most myeloma patients, however, only receive a single auto HCT. Many of these patients are eligible for a second auto HCT as salvage at the time of relapse. We evaluated the outcome of salvage auto HCT for MM patients treated at our institution. Methods We performed a retrospective chart review and identified 62 MM patients (38 males, 24 females) who received a second auto HCT as salvage between 1/3/1992 and 11/4/2008.. Preparative regimen was high-dose melphalan alone or in combination with other chemotherapy agents, including busulfan, topotecan and bortezomib. Three patients received a combination of thiotepa, busulfan and cyclophosphamide. Results Median interval between the first and salvage auto HCT was 21 months (range 2-81). Median age at salvage HCT was 55 years (37-73) and median prior treatment regimens were 4 (range 2-16). Twelve patients had chromosomal abnormalities on conventional cytogenetic studies. Patients received a median CD34 cell dose of 4 ×106 / kg (range 2.3-11.2). Fourteen patients (22%) experienced grade 3 or higher toxicity after the salvage auto HCT. Two patients died within 100 days with a TRM of 3%. Median time to neutrophil engraftment was 10 days (8-38). Responses after salvage auto HCT were as follows: CR+ near CR 15%, PR 48%, with an overall response rate of 63%. Twenty-seven (44%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 25 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) were 15.5 and 43.3 months, respectively. Median time to progression after the first and salvage auto HCT was 20 and 12 months, respectively, with total remission duration of 32 months from two HCTs. Median OS from the time of diagnosis was 72 months, comparable to reported results with tandem auto HCT. At last follow up, 20 patients were alive and in remission. Conclusions In selected MM patients a second auto HCT for salvage therapy is well tolerated with acceptable toxicity. The combined remission duration and overall survival are comparable to outcomes with tandem autotransplants. Disclosures Qazilbash: Cephalon: Speakers Bureau.

Long Term Outcome After Low Dose TBI Based Conditioning Hematopoietic Stem Cell Transplantation (HSCT) From Related and Unrelated Donors for Older Patients with AML

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2030-2030
Author(s):  
Dietger Niederwieser ◽  
Leo F Verdonck ◽  
Jan J Cornelissen ◽  
Michael Cross ◽  
Rainer Krahl ◽  
...  
Keyword(s):  
De Novo ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Study Groups ◽  
Long Term Results ◽  
Term Outcome ◽  
Hematopoietic Stem ◽  
Long Term Outcome

Abstract Abstract 2030 HSCT after reduced or minimal intensity conditioning is increasingly used to treat AML patients not eligible for conventional HSCT. Short term outcome has been reported frequently and risk factors have been identified; long term results still await in depth evaluation. We report here 5 years follow up results from a prospective phase II study conducted by two AML study groups in Europe. Patients were recruited from AML protocols HOVON/SAKK AML 43 and the OSHO AML 1997 study. The regimen consisted of fludarabine (FLU), 30 mg/m2/d on days −4, −3, and −2, 2 Gy TBI on day 0 (the day of HSCT) with mycophenolate mofetil, [15 mg/kg p.o. b.i.d. from 5 hours after HSCT to day +40], and cyclosporine, [CSP; 6.25 mg/kg p.o. bid from day –3 to day +180] after HSCT. Cyclosporine was adjusted to trough levels and reduced according to a predetermined tapering schedule and donor type. A total of 96 patients were recruited between 5/2002 and 8/2005 in the study. Age was median 62 (range 40 – 74) years, 54 patients were male (56%) and 73 patients (76%) had de novo AML. The remission status on entry was CR1 in 83 (86%) patients and CR2 in 13 (14%). Of the 96 patients, 20% had high risk cytogenetics and SCT was performed a median of 75 days after chemotherapy. There were no statistical differences in the above described characteristics except for more secondary AML (p=0.04) and more CR2 patients (p=0.07) among the 59 unrelated SCT (61%) as compared to the 37 related SCT (39%). Graft rejection at two years was observed in 6% of the patients. Absence of chronic GvHD was diagnosed in 40% and limited chronic GvHD in 29% of the patients, with no difference between related and unrelated SCT. Probability of overall survival (OS) at 6 years with a median follow up of 64 (49–92) months reaches a plateau after 5 years at 0.33±0.05 and was not significantly better in CR1 than in CR2. However, there was a trend towards better OS at 6 years for unrelated 0.41±0.11 as compared to related 0.29±0.07 SCT (p=0.08) in CR1 only. This difference was significant for disease free survival (DFS) (0.48±0.09 unrelated vs 0.27±0.06 related; p=0.04), the major reason being a higher relapse rate in related as compared to unrelated SCT (0.62±0.08 vs 0.40±0.09). The overall non-relapse mortality at 6 years was 0.21±0.05. We conclude that OS and DFS reach a stable plateau from 5 years after SCT to more than 8 years after SCT. In CR1 patients, DFS is superior after unrelated as compared to related SCT. Accordingly, strategies designed to decrease relapse, especially after related SCT, have already been implemented in the ongoing protocols. The preferential use of unrelated rather than related donors may be beneficial and should be considered in future protocols. Disclosures: Off Label Use: Transplantation in elderly patients.

Comparison of Autologous and Allogeneic Transplantation As Therapy of First Relapse in Patients with Multiple Myeloma - Long-Term Follow up Analysis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4124-4124
Author(s):  
Ute Hegenbart ◽  
Stefan O Schonland ◽  
Axel Benner ◽  
Christina Wunder ◽  
Thomas M. Moehler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Chronic Gvhd ◽  
High Dose ◽  
Two Stage ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
First Relapse ◽  
First Diagnosis

Abstract Abstract 4124 BACKGROUND: Most patients (pts) undergoing high-dose therapy with melphalan 200 mg/m2 (HDM) and autologous transplant for multiple myeloma (MM) develop disease recurrence. The optimal salvage treatment including autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (SCT) as consolidation therapy for these patients is not yet defined. METHODS: We performed a retrospective analysis of 116 pts with MM treated in our institution between 1999 and 2005. Inclusion criteria were relapse after auto-SCT (n=88) or failure of induction treatment (n=28) and age ≤ 65 years. Re-induction was performed with TCED (thalidomide, cyclophosphamide, etoposide and dexamethasone (Möhler et al, Blood 2001). Seventy-one pts (median age, 59 yrs) received auto-SCT (auto-group) after HDM followed by maintenance therapy with thalidomide or interferon-alpha in 42 pts. Forty-five pts (allo-group, median age, 53 yrs) underwent a reduced-intensity allo-SCT (related in 24 pts), mostly using conditioning with 2 Gy total body irradiation and fludarabine. Thirty-eight pts received an auto-allo-tandem-SCT (Maloney, Blood 2003) and 7 pts have been directly transplanted after TCED. Statistical analysis was done using the two-stage test of Qiu & Sheng (JRSS Ser. B 2008) to compare two possibly crossing survival curves. Extended Cox proportional hazards regression models were applied to allow for time-varying differences between the two SCT groups. RESULTS: Estimated median follow-up after start of TCED was 95 months. All pts received a median number of 3 TCED cycles for re-induction therapy. 64 of 116 pts (55%) showed at least a PR after TCED chemotherapy (CR in 3 pts). TRM was 17% after 2 years in the allo-group and differed significantly from the auto-group (3%, p=0.02). More CR were achieved after allo-SCT compared to auto-SCT (17 vs. 4 pts., p<0.001). Median overall survival (OS) was 26 months for the auto group and 23 months for the allo group (Figure 1, p=0.16). Median progression-free survival (PFS) was 12 months for both groups but crossing hazards were observed (Figure 2, p=0.03, two-stage test of Qiu & Sheng). The results of multivariate regression analysis for OS and PFS including age at relapse-SCT, response to TCED, time between first diagnosis until first relapse-SCT and primary progression are shown in table 1. In the allo group, there was no OS or PFS difference between related and unrelated donors (multivariate analysis). Cumulative incidence of chronic GvHD was 73% (53% extensive). Patients with chronic GvHD showed a better OS and PFS than pts without (univariate analysis, both p<0.01). CONCLUSIONS: To our knowledge, this is the first analysis in a large number of patients with a long follow-up comparing allo with auto SCT in 1st myeloma relapse which were treated uniformly with TCED therapy for re-induction. Main problem was MM recurrence. However, younger pts with disease response after TCED and longer time from first diagnosis to first SCT after relapse profit best from TCED and this transplant approach. Most interestingly, disease control is better after allo compared to auto SCT in univariate and multivariate analysis leading to a PFS of about 20% after 4 years. In our opinion, allo SCT is a valuable clinical option for patients with 1st relapse after HDM and auto SCT. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplant in Advanced Multiple Myeloma: Experience from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5536-5536
Author(s):  
Yizel Elena Paz Nuñez ◽  
Beatriz Aguado Bueno ◽  
Isabel vicuña Andrés ◽  
Ángela Figuera Álvarez ◽  
Miriam González-Pardo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematopoietic Stem

Abstract Introduction The prognosis of patients with multiple myeloma (MM) has improved in the last years due to the important advances in the knowledge of the biology of the disease, the implementation of new drugs and the incorporation of autologous hematopoietic stem cell transplant (autoHSCT). The allogenic hematopoietic stem cell transplant (alloHSCT) continues to be controversial: it offers a curative potential but with the cost of high toxicity, limiting the procedure to those young patients with a high-risk disease. This procedure shall be performed in expert centers and, whenever possible, in the context of a clinical trial. In the following we describe the experience of our center with alloHSCT in advance multiple myeloma patients. Patients and methods A total of 18 patients were diagnosed with multiple myeloma received an alloHSCT during a 13 year period (1996-2013), with a median age of 46 ± 5.9 years. All of our patients received an allogenic HLA matched sibling donor with reduced-intensity conditioning. The majority of patients were transplanted because of advanced disease, relapse after an autologous transplant or as part of a sequential transplant in patient with a high risk disease. One patient received, in two occasions, an alloHSCT. Around 70% of patients had received more than 3 previous lines of treatment including, in nearly 95%, an autoHSCT. Patient's characteristics can be found on table 1, characteristics of the procedure can be found in table 2.Table 1.Patient«s CharacteristicsN (%)GenderMale Female10 (55,5%) 9 (44,4%)Secreted ProteinIgGκ IgG λ IgA κ BJ Plasmocitoma8 (44,4%) 4 (22,2%) 2 (11,1%) 3 (16,7%) 1 (5,6%)Debut DS stageII-A II-B III-A III-B Plasmocitoma5 (27,8%) 1 (5,6%) 8 (44,4%) 3 (16,7%) 1 (5,6%)Cytogentics at diagnosisMissing Unfavorable Favorable10 (55,5%) 6 (33,3%) 2 (11,1%)Previous lines of treatment²2 3-4 ³56 (33,3%) 10 (55,5%) 2 (11,1%)Previous autoHSCTYes No17 (94,5%) 1 (5,6%)Previous radiotherapyYes No8 (44,4%) 10 (55,6%)Disease status at transplantComplete remission Partial remission Relapse9 (50,0%) 3 (16,7%) 6 (33,3%)Table 2.Treatment characteristicsN (%)Conditioning regimenMyeloablative Reduced-intensity6 (33,3%) 12 (66.7%)Stem cell sourceBone marrow Peripheral blood4 (22.2%) 14 (77.8%)GVHD prophylaxisCsA+MTXCsA+CSCsA+MMF10 (55.6%) 3 (16.7%) 5 (27.8%)InfectionsYes No16 (88.9%) 2 (11.1%)MucositisYes No12 (66.7%) 6 (33.3%)Acute GVHDYes II-IV III-IV No4 (22.3%) 3 (16.7%) 1 (5.6%) 14 (77.8%)Chronic GVHDNo Limited Extensive8 (44.3%) 5 (27.8%) 5 (27.8%) Results: Transplant related mortality (TRM) before day 100th was one case due to a thromboembolic event. Global TRM was 16.6% (3 cases). The incidence of acute graft versus host disease (aGVHD) was 22%, controlled on most cases when corticosteroids were initiated. More than half of the patients developed chronic graft versus host disease (cGVHD), with an equal distribution on either presentation as limited or extensive. (Table 2) The total number of patients eligible for analysis was 17 (one patient was lost on follow-up). With a median follow up of 11 years, the overall survival (OS) was of 8.06 years [IC 95% 4,33-11,78] (figure 1.) and the estimated progression free survival (PFS) was of 25.83 months [IC 95% 8.87-42.79](figure 2). A total of 5 (29,4%) patients are still alive and 2 (11,7%) of them are in complete remission, of these 1 patient did not have a previous autoHSCT with a follow up of almost 15 years. Conclusions: Our results are similar to those reflected on the literature1-2. However we have to point out that our population is homogenous with advanced MM with more than 3 previous lines of treatment including in most cases auto-HSCT. In spite of this, morbility and mortality in our cohort was acceptable with the limitation of a high rate of cGVHD. There is a need of more studies including more patients to evaluate the role of alloHSCT in the era of new drugs for MM. References 1. Rosi-ol L et al. Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single institution. Bone Marrow Transplant. 2015. 2. Beaussant Y et al. Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Retrospective Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Biol Blood Marrow Transplant. 2015 Disclosures Alegre: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma for Long-Term Follow-up: Single Center Results

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5836-5836
Author(s):  
Weiwei Sui ◽  
Dehui Zou ◽  
Gang An ◽  
Shuhui Deng ◽  
Yan Xu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
First Line ◽  
Hematopoietic Stem ◽  
Agent Based ◽  
Total Treatment ◽  
Long Term Follow Up ◽  
Baseline Characteristics

Abstract Objective: To evaluate the efficacy and long-term outcome of the total treatment of induction therapy, ASCT and consolidation and maintenance therapy. Methods: A retrospective analysis was made on in multiple myeloma patients in our center between April 1, 2003 and February 1, 2016. The 157 patietns received autologous hematopoietic stem cell transplantation and review the autologous transplantation of long-term follow-up results. Analysis of the effect of transplantation efficacy, the impact on survival remission of different transplantation depth, transplantation in first line or not, salvage transplantation, prognosis of different staging system and other factors. Results: The baseline characteristics of the patients were shown in table 1. Overall patient ASCT before total effective rate (ORR) was 93.6%, in which the complete remission (CR) ratio was 33.1%. After ASCT, the best treatment response rate of PR was 80.3%, and the rate of CR was 58.6%. 91.69 months of median follow-up, patients with an overall survival (OS) and progression free survival (PFS) respectively 91.69 and 50.76 months; in 2005 before the median OS and PFS 39.0m and 23.0m. In 2005 after respectively and 56.41m 120.90m, P = 0.000. The median OS and PFS in the first line transplantation group and salvage transplantation group were vs 54.21m 39.0m and vs 7.09m 119.0m (P value was 0). 136 cases of patients with R-ISS stage, I, II, III of the patients with the median survival time were 120.90m (n=46), 86.43m (n=69), 35.65m (n=21), there were significant differences between groups, p=0.000. Each period of PFS were 72.11m, 51.84m, 28.09m, I and II, III,, p=0.001 and p=0.03, while there was no significant difference between II and III, p=0.122. The received autologous transplantation as first-line and salvage treatment of patients with subgroup survival analysis, median OS of the R-ISS stage III patients and different 15.84m 35.65m, P = 0.031; two groups of patients the median PFS (phase I: 91.69m vs18.92m; II: vs 16.69m 53.42m; phase III: vs 5.91m 28.52m) have difference (P = 0.000). In the first-line transplantation group, transplantation is more than or equal to PR and did not get effective PR group between OS were significantly different; before transplantation achieved CR, PR but did not obtain Cr and did not get effective PR group between PFS were significantly different; after transplantation and achieved CR CR did not get the patients had a median PFS were 65.57m 48.13m, P = 0.039 and median OS no difference. Accept any kind of noval agent- based chemotherapy were significantly longer OS and PFS than traditional chemotherapy (P = 0.001, P = 0.004) .There was no obvious difference on median OS between based regimen (bortezomib group median OS: NR; thalidomide group:120.90m); PFS in thalidomide group (median PFS : NR vs 54.21m) significantly prolonged (P = 0.010). By comparing the baseline characteristics of the two groups, it was found that the PFS was significantly shorter in the bortezomib group with an extra medullary lesion. Multivariate analysis showed that only R-ISS and the depth of remission before transplantation had effect on OS (p=0.003) and PFS (p=0.036) respectively. Conclusion: The total treatment of novel agent-based chemotherapy and ASCT for transplantation-eligible multiple myeloma patients is effective, further improve the remission rate and remission depth, prolong PFS and OS, the overall median survival up to 120.9m. First line transplantation can significantly prolong the OS and PFS compared with salvage transplantation. R-ISS and pre-transplant remission depth are prognostic factors influencing survival of patients. The total treatment to thalidomide based without extramedullary perhaps makes patients get long-term survival. Disclosures No relevant conflicts of interest to declare.

CULMINATE: A phase II study of cusatuzumab + azacitidine in patients with newly diagnosed AML, ineligible for intensive chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS7565-TPS7565 ◽  
Author(s):  
Geralyn Carol Trudel ◽  
Angela J. Howes ◽  
Neelum Jeste ◽  
Jeffrey J. Tryon ◽  
Liang Xiu ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Standard Dose ◽  
Intensive Therapy ◽  
Moderate Hepatic Impairment ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Hematopoietic Stem

TPS7565 Background: AML, the most common acute leukemia in adults, is a heterogeneous malignancy characterized by uncontrolled clonal expansion of hematopoietic progenitor cells. Median diagnosis age is ~67 yrs. Despite current therapies prognosis is poor with 5-yr OS ~25% for patients (pts) ≥65 yrs. For pts unable to receive intensive chemotherapy, survival rates are worse, indicating a critical need to develop better treatments. CD70 is expressed on >95% of AML blasts harvested from newly diagnosed AML pts but not on normal hematopoietic stem cells nor most normal tissues. Cusatuzumab is a first-in-class, high-affinity anti-CD70 monoclonal antibody with multiple mechanisms of action, including Fc-mediated cytotoxicity with enhanced ADCC and inhibition of CD70/CD27 signaling, resulting in leukemia blast and stem cell cytotoxicity. As cusatuzumab and azacitidine target distinct pathways of myeloblast propagation, a combination may have a synergistic therapeutic effect and overcome treatment resistance. Initial data from a Phase I study (NCT03030612) with cusatuzumab (1–20 mg/kg) + standard dose azacitidine in AML pts ineligible for intensive chemotherapy showed no dose-limiting toxicity and a CR/CRi (CR with partial/incomplete hematologic recovery) in 10 of 12 pts (ASH 2019, Abs #234). This abstract describes a follow-on Phase II study (NCT04023526). Methods: CULMINATE is a 2-part study of cusatuzumab + azacitidine to determine the optimal dose of cusatuzumab (Table). Inclusion criteria: ≥18 yrs with de novo or secondary AML unfit for intensive therapy (≥75 or <75 yrs with a comorbidity [i.e. ≥1 of: ECOG 2, severe cardiac/pulmonary or moderate hepatic impairment]). In Part 1, pts are randomized 1:1 to cusatuzumab 10 or 20 mg/kg (IV, on Days 3 and 17 of each 28-day cycle) + azacitidine (75 mg/m2 SC or IV on Days 1–7). Data will be reviewed after 15, 30 and 50 pts are enrolled into each arm to select the cusatuzumab dose for the Part 2 expansion cohort in which efficacy and safety will be further evaluated. Follow-up continues until death, loss to follow-up or study end. The primary objective is to determine CR rate. Secondary objectives include rate of CRi/CRh, rate of MRD-negativity, ORR, time to and duration of response, pharmacokinetics, immunogenicity, transfusion independence and safety. Enrollment began in Sept 2019 and is currently two-thirds complete. Clinical trial information: NCT04023526 . [Table: see text]

Results from Two Consecutive Studies of Consolidation Therapy after Autologous Transplant for Multiple Myeloma: Thalidomide, Dexamethasone, and Clarithromycin or Lenalidomide, Dexamethasone, and Clarithromycin

2017 ◽  
Vol 137 (3) ◽  
pp. 123-131 ◽  
Author(s):  
Leona A. Holmberg ◽  
Pamela S. Becker ◽  
William Bensinger
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Randomized Study ◽  
Single Agent ◽  
Survival Rates ◽  
Immunomodulatory Drugs ◽  
Hematopoietic Stem ◽  
Good Disease Control ◽  
Disease Free

Background: In multiple myeloma (MM), relapse is a problem after autologous hematopoietic stem cell transplantation (ASCT). In the nontransplant setting, thalidomide/dexamethasone/clarithromycin (BLT-D) and lenalidomide/dexamethasone/clarithromycin (BiRd) achieve responses with acceptable toxicity. Both regimens are reasonable objects of study in the post-ASCT setting. Patients and Methods: We report on BLT-D and BiRd given post-ASCT. Studies were conducted consecutively. After recovery from ASCT, therapy was started. All 3 drugs were given for 1 year, and then immunomodulatory drugs alone were given as long as tolerated or until disease progression. Results: For BLT-D, the most common toxicity was peripheral neuropathy (PN). For BiRd, infection, PN, and neutropenia were the most common adverse events. BiRd was associated with a higher frequency of secondary cancers. The median follow-up for BLT-D was 10.2 years (range 8.6-10.7) and for BiRd it was 7.5 years (range 6.4-8.4). After BLT-D, 18 patients (67%) were alive and 10 (37%) were alive without disease progression, and after BiRd, 18 patients (58%) were alive and 10 (32%) were alive without disease progression. Conclusions: BLT-D and BiRd can be given post-ASCT with different toxicity profiles and comparable disease-free and overall survival rates. A randomized study comparing these regimens to single-agent lenalidomide is needed to determine which approach is superior. Key Message: Relapse of MM is a major problem after ASCT. Strategies are needed post-ASCT to improve outcomes. In the nontransplant setting, thalidomide or lenalidomide/dexamethasone/clarithromycin treat MM with acceptable toxicity. We, thus, studied both regimens post- ASCT. They can be given with different toxicity profiles and result in good disease control.

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