Clinical Features, Outcome and Prognostic Factors For Survival and Evolution To Multiple Myeloma Of Solitary Plasmacytomas: A Report Of The Greek Myeloma Study Group In 97 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3130-3130
Author(s):  
Eirini Katodritou ◽  
Evangelos Terpos ◽  
Argiris S. Symeonidis ◽  
Anastasia Pouli ◽  
Charikleia Kelaidi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Plasma Cells ◽  
Surgical Excision ◽  
Novel Agents ◽  
High Dose ◽  
Solitary Plasmacytoma ◽  
Prognostic Impact ◽  
Free Survival

Abstract Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary tumors consisting of monoclonal plasma cells, without evidence of systematic multiple myeloma (MM). The treatment of choice is local radiotherapy (RT) with or without surgical excision (SE). Our aim was to describe the clinical features, the outcome and prognosis of SP patients. Thus, we studied 97 consecutive patients, 65 with solitary bone plasmacytoma (SBP) and 32 with solitary extramedullary plasmacytoma (SEP), (M/F: 66/31, median age: 61 years, range 17-85 years) who were diagnosed and treated in 12 Greek Myeloma Centers; treatment was given according to each center’s local policy. Patients with SBP and SEP did not differ in age, gender, performance status (PS), Hb, CRP, LDH, calcium, beta2-microglobulin, renal function or impairment of humoral immunity (immunoparesis). Patients with SEP presented more often with serum or urinary monoclonal component (p<0.001 and p=0.004, respectively). The median size of SP was larger in patients with SBP compared to patients with SEP (5.5cm vs. 3cm; p=0.003). CD56 antigen was expressed more often on plasma cells of SBP biopsies (p=0.03). Eighteen (56.2%) patients with SEP presented with upper respiratory track plasmacytoma and 14 presented with plasmacytomas in other locations. In 26/65 patients (40%) with SBP, plasmacytoma was located in the vertebrae and 39 had plasmacytoma in other bones. Bisphosphonates were administered more frequently in SBP patients (p=0.001). There was no difference in the type of treatment (RT, conventional chemotherapy (CT) ± novel agents (NA), SE or combined treatment) between the 2 groups; 80 patients (82.5%) received RT alone or in combination with CT and/or SE, 7 patients (7.2%) received CT alone, 7 patients (7.2%) underwent only SE and 3 patients (3.1%) were treated with CT and SE. The median dose of radiation delivered was 40 Gy (range 24-55 Gy). Novel agent combinations were administered in 27/47 patients (57.4%) who received CT (bortezomib-based regimens: 46.8%); 13/47 (27.6%) patients treated with CT underwent high-dose therapy. Myelotoxicity, neurotoxicity and neutropenic infections presented more frequently in patients treated with CT (p<0.001, p=0.01, p=0.009, respectively). Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively. There was no difference in response rates or median time to response (3 months, range 1-24 months) between patients with SBP or SEP. Overall, 38 (39.2%) patients relapsed (relapse of SP only: 14; progression to MM only: 16, relapse of SP and progression to MM: 8). After a median follow up of 60 months (range 3-264 months), 74 (76.3%) patients were alive, 13 (13.4%) were dead and 10 (10.3%) patients were lost to follow up. Overall survival (OS), although higher in SEP over SBP, did not reach statistical significance. The 10-year MM-free survival (MMFS) was 50% vs. 70% respectively, for patients with SBP vs. SEP (p=0.054). Ten-year OS for patients treated with RT± surgical excision was 81% vs. 70% for those treated with other therapies including CT± NA (p=0.3). Overall, the 10-year OS, plasmacytoma relapse-free survival (PRFS), progression-free survival (PFS) and MMFS was 78%, 58%, 43% and 59%, respectively. In the multivariate analysis PRFS and age predicted for OS (p=0.02, HR: 0.97; 95% CI: 0.94-0.99 and p=0.01, HR: 1.09; 95% CI: 1.017-1.16, respectively); 10-year OS for patients <60 vs. ≥60 years was 85% vs. 60% (p=0.02); patients with PRFS >24 vs. ≤24 months had a 10-year OS of 82% vs. 60% (p=0.01). Achievement of CR predicted positively for PRFS. Immunoparesis (n=24) predicted negatively for progression to MM. Chemotherapy including NA had no prognostic impact on OS, PRFS or MMFS. Our study demonstrated that patients with SP enjoy a prolonged OS that is favorably influenced by young age and PRFS. We also confirmed that patients with SBP progress more frequently to MM compared to SEP in the era of novel agents. Radiotherapy with or without SE remains the treatment of choice for SP. The additional use of systematic therapy including novel anti-myeloma agents increases toxicity without improving survival or decreasing the probability of SP relapse or progression to MM. Immunoparesis predicts for progression to MM. Disclosures: No relevant conflicts of interest to declare.

Prognostic Value of Immunophenotyping in Multiple Myeloma: A Study by the PETHEMA/GEM Cooperative Study Groups on Patients Uniformly Treated With High-Dose Therapy

2008 ◽  
Vol 26 (16) ◽  
pp. 2737-2744 ◽  
Author(s):  
Gema Mateo ◽  
M. Angeles Montalbán ◽  
Maria-Belén Vidriales ◽  
Juan J. Lahuerta ◽  
Maria V. Mateos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Study Groups ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Multiparametric Flow Cytometry ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Purpose To analyze the prognostic impact of immunophenotyping in patients with multiple myeloma (MM). Patients and Methods We have prospectively analyzed the prognostic impact of antigenic markers, assessed by multiparametric flow cytometry, in a series of 685 newly diagnosed MM patients that were uniformly treated according to the GEM 2000 protocol. Results Our results show that expression of both CD19 and CD28 as well as the absence of CD117 were associated with a significantly shorter progression free-survival (PFS) and overall survival (OS). Interestingly, the CD28 expression correlated with t(14;16) and del(17p), while CD117-negative patients were associated with t(4;14) and del(13q). Simultaneous assessment of CD28 and CD117 antigens allowed stratification of patients with MM into three risk categories: poor risk (CD28 positive CD117 negative), intermediate (either both markers negative or both positive), and good risk (CD28 negative CD117 positive), with PFS rates of 30, 37, and 45 months, respectively (P = .01), and OS rates of 45, 68, and not reached, respectively (P = .0001). Conclusion To the best of our knowledge, this is the first prospective analysis in which the prognostic impact of a relatively high number of antigenic markers has been simultaneously analyzed in a large series of uniformly treated patients, showing that the expression of several antigens (particularly CD28 and CD117) on bone marrow plasma cells from patients with MM can help to identify patients at high risk of progression.

Combination of Bortezomib and Dexamethasone (VD) or Bortezomib, Adriamycine and Dexamethasone (PAD) Followed by High Dose Therapy and Peripheral Blood Stem Cell Transplantation in First-Line Treatment of T(4;14) Multiple Myeloma : a Prospective Study of the MAG Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3408-3408
Author(s):  
Lionel Karlin ◽  
David Ghez ◽  
Marie-Olivia Chandesris ◽  
Sylvain Choquet ◽  
Margaret Macro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood Stem Cell ◽  
Induction Treatment ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Blood Stem Cell Transplantation

Abstract Abstract 3408 Poster Board III-296 The t(4;14)(p16.3;q32), leading to the ectopic expression of two potential oncogenes, the Multiple Myeloma Set Gene (MMSET) and the Fibroblast Growth Factor 3 (FGFR3), is found in 15% of patients with multiple myeloma (MM) and is associated with a very poor prognosis. We previously shown in patients under 65 years of age that High Dose Therapy followed by Peripheral Blood Stem Cell Transplantation (HDT-PBSCT) provides a high response rate (RR) but a very short median relapse-free survival of only 11 months. In addition, relapses are often aggressive and chemoresistant. Thus, more effective regimen is urgently needed. We prospectively studied 23 t(4;14) MM patients treated with 3 or 4 cycles of a combination of Bortezomib and Dexamethasone (VD) (n=4) or of Bortezomib, Adriamycine and Dexamethasone (PAD) (n=19) as induction treatment before HDT-PBSCT (Melphalan 200 mg/m2). T(4;14) was detected using real time quantitative PCR searching for IGH/MMSET and FGFR3 transcripts. RR, event-free survival (EFS) and overall survival (OS) were evaluated. Median age at diagnosis was 51 years (range, 33-64). Isotype was IgA in 12 (52%) patients. All patients had stage II or III MM. An elevated serum β2m level (>3.5 mg/L) was found in 14 (61%) patients, and a low haemoglobin (Hb) level (<10 g/dL) in 10. Four presented with renal failure and 5 with hypercalcemia. Three (16%) of 19 patients had a t(4;14) without expression of FGFR3. After induction treatment with VD or PAD, PBSC were successfully harvested with granulocyte-colony stimulating factor only (n=15) or following a cycle of high-dose cyclophosphamide (n= 7). RR after induction treatment was complete response (CR) in 6 (26%) patients, very good partial response (VGPR) in 9 (39%), partial response (PR) in 3. Five patients had refractory or progressive disease (PD), including 1 who died before stem cell mobilization. RR after HDT was CR in 11 (48%), VGPR in 4 (17%) and PR in 4 (overall RR of 82%). Three had PD. With a median follow-up of 18 months (range, 3-32), 9 (39%) patients are alive without relapse, including 4 with a 19, 27, 30 and 32 months follow-up respectively. Twelve (52%) patients relapsed. Two patients died in the first month post HDT from PD. We found a median EFS and OS from initiation of therapy of 14.7 and 30.9 months respectively. EFS was not influenced by Hb and/or serum β2m level. However, we found a significantly longer OS in patients with low β2m (median non reached) as compared to patients with high β2m (median=23.1 months, p=0.04). These preliminary results illustrate the heterogeneity of this disease and indicate that some t(4;14) MM patients seem to benefit from bortezomib containing regimen as induction treatment before HDT in term of EFS and OS. A larger series with a longer median time of follow up will be presented. Disclosures: No relevant conflicts of interest to declare.

Multiple Myeloma Profile In Latin America: Clinical and Epidemiological Observational Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5327-5327
Author(s):  
Vania T M Hungria ◽  
Angelo Maiolino ◽  
Gracia Aparecida Martinez ◽  
Carmino A De Souza ◽  
Rosane Bittencourt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Clinical Features ◽  
Median Overall Survival ◽  
High Dose Chemotherapy ◽  
Patterns Of Care ◽  
Disease Stage ◽  
High Dose

Abstract Introduction Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries. Objective To characterize the demographic and clinical features of patients with multiple myeloma from five LA countries (Brazil, Argentina, Chile, Mexico and Peru) and to create a LA database on MM; in addition to investigating the patterns of care for MM patients in Latin America. Patients and Methods This is an observational, non-intervention study, with a prospective evaluation of data. Eligible patients were diagnosed with multiple myeloma, between January 1, 2005, and December 31, 2007, at any one of the participating centers, regardless of disease stage or treatment modality. The follow-up period extended to at least 5 years for each patient (December 31, 2012). Results Eight hundred and seventy six patients were included. The median age was 60 years old (25-97), 53.4% male and 46.6% female. The median follow-up was 31.4 months, and the median overall survival was 57 months. The median overall survival to patients who received high-dose chemotherapy was 77 months and for patients who received conventional chemotherapy was 48 months (p<0.001). The multivariate prognostic model included patient baseline variables that were associated with mortality in the Kaplan-Meier univariate analyses. Only hypercalcemia, DSS II and III, ISS stage III andnon- high-dose chemotherapy were independent predictors of mortality. Conclusion This current study, which is the largest case series of MM patients in Latin America, recognizes the feasibility of large, collaborative, observational studies among various tertiary-care hematology centers in Latin America. Note We will present more details related to the demographic and most frequently used treatments in Latin America for newly diagnosed and relapsed patients in these LA countries. Disclosures: No relevant conflicts of interest to declare.

A Randomized Comparison of Total-Marrow Irradiation, Busulfan and Cyclophosphamide with Tandem High-Dose Melphalan in Patients with Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 728-728
Author(s):  
Stefan Knop ◽  
Katja Bauer ◽  
Holger Hebart ◽  
Hannes Wandt ◽  
Lorenz Trumper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Plasma Cells ◽  
Disease Free Survival ◽  
Marrow Transplant ◽  
High Dose ◽  
Newly Diagnosed ◽  
Peripheral Blood Stem Cells ◽  
Free Survival ◽  
Total Marrow Irradiation

Abstract Background Myeloablative chemotherapy with support of autologous peripheral blood stem cells (APBSC) has widely been accepted as a standard of care in patients (pts) with newly diagnosed multiple myeloma (MM). High-dose (HD) melphalan (Mel) 200 mg/m2 was considered superior to total-body irradiaton (TBI) plus Mel 140 mg/m2 for toxicity reasons. Since MM plasma cells are inherently responsive to irradiation, our group evaluated TBI aimed at reduced organ toxicity by shielding lungs and liver (total-marrow irradiation [TMI], 9 Gy) combined with busulfan (Bu, 12 mg/kg) and cyclophosphamide (Cy, 120 mg/kg) in a previous phase I/II trial (Einsele et al, Bone Marrow Transplant, 2003). Patients and methods In the current study (DSMM I), subjects with previously untreated MM in Durie-Salmon stages II/III were randomly assigned to either receive one course of TMI/Bu/Cy versus two cycles of HD Mel 200 mg/m2 each with APBSC transplantation if having had an adequate number of stem cells collected and at least stable disease. Primary end point was event-free survival (EFS), secondary end points overall (OS) and disease-free survival (DFS). Results A total of 294 pts (median age, 54 years), 246 of whom completed stem cell harvest were enrolled between 8/1998 and 1/2002 by 46 centres. Eventually, 198 (n=100 TMI/Bu/Cy and n=98 HD Mel) pts were randomized and included into the ITT population. The safety population (n=80 TMI and n=118 HD Mel, due to 18 pts switching to Mel) was analyzed for toxicity and response. CR rate before HD therapy was 7.0% (7/100) in the TMI and 6.1% (6/98) in the Mel arm respectively. Significantly more pts receiving TMI/Bu/Cy experienced WHO grades 3 and 4 pulmonary and gastrointestinal toxicity and pain. Following HDT, CR rate increased to 17.5% (14/80, TMI) and 32.2% (38/118, HD Mel; p=.022) respectively. After a median follow-up of 1447 days, median EFS in the TMI group was 1161 days versus 1090 days for HD Mel (p=.812). Probability of 4-year OS was 72.7% (95%-CI: 62.1–80.7) with TMI and also 72.7% (95%-CI: 61.7–81.1) after HD Mel (p=.754). For pts in CR following HD therapy, probability of 4 year DFS was 62.4% (95%-CI: 33.6–81.6) for TMI vs. 50.4% (95%-CI: 30.6–67.3) for HD-Mel (p=.138). Conclusion In this randomized trial on pts with newly diagnosed MM, the irradiation-based regimen was associated with more pulmonary and GI toxicity when compared to HD Mel. Incidences of other toxicities including hepatotoxicity, however, were not different between the two treatment arms. CR rate was superior for HD-Mel, while there was no difference in OS and EFS between the two treatment arms. Subjects achieving CR may be more likely to enjoy prolonged DFS after TMI/Bu/Cy.

Achievement of CR and nCR Before and After First High-Dose Therapy Followed by Autologous Stem Cell Transplantation Is a Major Marker for Long-Term Survival in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3400-3400
Author(s):  
Hartmut Goldschmidt ◽  
Gerlinde Egerer ◽  
Ute Hegenbart ◽  
Markus Munder ◽  
Thomas Hielscher ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Significant Prognostic Factor ◽  
High Dose Therapy ◽  
Free Survival ◽  
Before And After ◽  
Duration Of Response

Abstract Abstract 3400 Poster Board III-288 To analyse the impact of complete response (CR), near CR (nCR) and very good partial response (VGPR) before and after first high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) on overall survival (OS) and progression-free survival (PFS), we evaluated all patients with multiple myeloma (MM) who underwent an ASCT in frontline treatment at our centre. The transplantations were performed between June 1992 and February 2009 giving a minimum follow up of 5 months after ASCT. The retrospective analysis included a total of 994 patients (579 males and 415 females) with a median age of 58 years at time of first ASCT (range 25 - 76 years). Median follow-up after first ASCT was 5.8 years. All patients suffered from symptomatic MM. Before induction treatment 48%, 31% and 21% of patients were in ISS-stage I, II and III, respectively. The following induction regimes were applied prior to HDT: VAD (n=683), TAD (n=74), PAD (n=64), and other regimes (n= 173). The patients were treated with HDT once (n= 460), twice (n=437) or thrice (n=97). 91 patients received an allogeneic SCT, 30 of these before first progression after ASCT. These were censored for PFS at time of allogeneic SCT. Maintenance therapy (interferon n=332, thalidomide n=203, bortezomib n=48 or others n=13) was administered in 596 patients. Overall survival and progression-free survival were calculated from the time of first ASCT. The median OS time was 5.7 years and the median PFS was 2.2 years. Log-rank test, univariate and multivariate Cox PH regression as well as landmark analyses were utilized to assess the prognostic impact of response. We analysed the effect of achievement of CR, of nCR or CR and of VGPR or CR or nCR before and after HDT, respectively. Achieving CR or nCR is a highly significant prognostic factor for PFS and OS before (p<0.001 and p=0.01, respectively) and after first HDT (both p<0.001). The group including VGPR showed superior outcome when assessed after HDT, driven by the effect of CR/nCR. When adjusting for the effect of age, beta-2 microglobulin before ASCT, albumin before ASCT, new drugs before ASCT (thalidomide and bortezomib; yes/no), second ASCT within 9 months (yes/no), maintenance therapy (yes/no), and date of first ASCT, achieving CR or nCR remained a significant prognostic factor (PFS after ASCT: HR=0.66 [0.54;0.80], p<0.001; OS after ASCT: HR=0.65 [0.51;0.83], p=0.001). In addition, we analyzed the effect of duration of response compared to response achievement per se. Patients who sustained their remission (overall response = PR and better) at 3 yrs after first ASCT had a favourable prognosis with respect to OS compared to patients losing remission. Conclusion: In our single-center cohort achieving CR or nCR before and after first HDT is highly prognostic for PFS and OS in MM. Sustained duration of response is also associated with an improved prognosis (3 years landmark analysis). At our centre we recommend that patients not achieving at least an nCR should be treated with a second cycle of HDT. Disclosures: No relevant conflicts of interest to declare.

Multiple Myeloma Patients Who Are Chemosensitive and Present with Plasma Cells Lacking Phosphorylated Retinoblastoma and/or Cyclin A Expression Benefit From High Dose Therapy and Autologous Stem Cell Transplantation More.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1345-1345
Author(s):  
Selami Kocak Toprak ◽  
Gulsah Kaygusuz ◽  
Nazmiye Kursun ◽  
Duygu Ozu ◽  
Merih Kizil Cakar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Initial Treatment ◽  
Plasma Cells ◽  
Cyclin A ◽  
Response To Therapy ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Group 1

Abstract Abstract 1345 Background and aim: Multiple Myeloma (MM) plasma cells are known to posses low replicative potential and plasma cell labelling index is generally accepted as a strong prognostic factor. TC classification of MM defines categories of myeloma cases expressing different cyclins (Fonseca et all, Leukemia 2009). Although cyclin dependent kinase inhibitors (CDKI) are important for cell cycle, they are not included in this molecular classification. Patients and Methods: With an aim to define high and low proliferative myeloma cases antibodies detecting cyclins (Cyc) A, D1, D2, D3, phosphorylated retinoblastoma (Rb), p16, p21, p27, Ki67 were applied to tissue sections obtained from either marrow plasmacytoma of 106 consequtive myeloma patients (median: 59, 32–79 years) diagnosed between 1998–2007. 100 patients <65 years (n:51) were evaluable for treatment outcome and received an induction of VAD (4-6 cycles), followed by a novel agent containing regimen (2-4 cycles) or autologous stem cell transplant (ASCT) depending on the response to induction. Postransplant consolidation or subsequent transplants were performed when < VGPR was obtained. Elderly patients (n:49) received induction for at least a year. Novel agents (Thalidomide: 66.7%, Bortezomib: 27.5%) were given in 94.2% of patients as ≥2 line treatment. Mann Whitney U, Kaplan-Meier or log rank analysis were performed using the SPSS version 15.0. Results: Loss of CDKI's were detected in 55.4–88.5 % of the cases. Cyclin D1D2D3 or Cyclin A expression was detected in 29.2, 21.7, 5.7 or 19.8 % of the cases. Rb was detected in 25%. Among the CDK's or CDKI's only Cyc D2 was correlated with Ki67 percentage (p=0.027). Loss of all CDKI's was observed in 31.1 %. The majority of p16 (-) cases were Cyc A (-) too (p=0.001). Loss of p16 and p 27 was observed more frequently than loss of p 21 (88 and 85% versus 54%). Patients were either both CycA and p21 (-) (50%) or both CycA and p21 (+) (31 %) (p=0.025). However there was no patient expressing Rb and p16. On the contrary, the majority patients were both Rb and p16 (-) (60%) (p=0.037). Groups of patients with high proliferative protential group 1 (Cyc D+ p16-), group 2 (CycA+ p21-), group 3 (CycA+ Rb+) and low proliferative protential group 4 (Rb- p16+), group 5 (CycA- Rb-) were analyzed. These were observed 42.5 %, 5.5%, 11.7%, 15.4% and 57.1%. No correlation could be found between the CDKI/Cyc defined risk groups and ISS, B2MG, LDH, CRP, OS. However among p16 (-) cases Rb (-) ones (n:39) had longer OS than Rb (+) patients (n:18) (49 vs 39 months). All p16 (+) patients were Rb (-) too and had a shorter OS (42 vs 84 months, p=0.006). Response to initial treatment was ≥ VGPR 16.8 %, ≥ PR 52%, refractory 21.4 %. High proliferative group 1 or patients with high LDH values had higher initial response rates (82.1 vs 53.8 %, p: 0.016 and 67.6 % vs 36 % p= 0.018). The deepest response was observed with initial treatment among 47.3 % and was improved following ASCT (18.3%). ASCT also improved OS among all (58 vs 34 months, p=0.0) but more strongly among Rb and/or CycA (-) patients (Table). The response to initial treatment did not influence OS. However if response is not upgraded following subsequent treatments OS deteriorated (5 year OS: 34 vs 44 months p=0.022) (Figure). These suboptimal responding patients could not be predicted by ISS, age, B2MG, high/low proliferating group definition. Although LDH was high in 72.7 vs 54.5 % of poor-responders this comparison was not significant. Conclusion: While depth of response to therapy did not, improvement of response with subsequent therapy ie novel agents or ASCT prolongged OS (34 vs 44 months, p=0.022) and was associated with lower LDH values. Compared to gene expression profilling, tissue array using monoclonal antibodies is a method which can be more widely applicable and in our study was able to define new prognostic parameters. Overall ASCT extended OS. This effect was stronger among patients lacking Rb and/or Cyc A, This finding echoes the need for better treatment modalities for patients with poorer prognosis ie Rb and/or Cyc A positivity. Multivariate analysis results will be presented during the congress. Disclosures: No relevant conflicts of interest to declare.

High Dose Therapy with Autologous Stem Cell Transplantation (HDT/ASCT) Support in Follicular Lymphoma (FL) a Very Long Follow-up Analysis of 640 Patients of Geltamo Spanish Group Suggests That FL Might be Cured, Even in High-Risk Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 675-675
Author(s):  
Ana Jiménez Ubieto ◽  
Carlos Grande García ◽  
Lucrecia Yáñez ◽  
Dolores Caballero ◽  
Silvana Novelli ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Retrospective Analysis ◽  
High Dose ◽  
Prognostic Impact ◽  
Second Malignancies ◽  
Free Survival ◽  
Number Of Patients ◽  
Histological Transformation

Abstract Background: Patients with high-risk FL intensified with HDT/ASCT may achieve prolonged remissions. The best timing for the procedure remains controversial. Patients who are transplanted in first response show a major Progression Free Survival (PFS) and Event Free Survival (EFS) advantage compared to those treated with conventional chemotherapy. Nevertheless, no randomized studies have yet shown an overall survival (OS) benefit. Populational-based and very long-term retrospective analysis are indispensable tools to assess the actual impact on outcome of therapeutic interventions in FL. With this assumption we performed a retrospective analysis in FL patients undergoing HDT/ASCT intensification included in the GELTAMO Spanish Group Registry. Objectives: The overall outcome as well as the clinical evolution according to the disease status at transplant, to the Follicular Lymphoma International Prognostic Index (FLIPI and FLIPI II) and to the previous exposure to Rituximab. Series characteristics: Six hundred and sixty six patients with FL (mean age 47 years, male 49%) undergoing HDT/ASCT between 1989 and 2007 were reported to the GELTAMO registry. Patients with histological transformation at the time of HDT/ASCT, those undergoing a 2nd transplant and those with a follow-up of less than 7 years were excluded. Thus, 640 patients were included in the analysis. Median follow-up was 12.2 years from HDT/ASCT and 14.2 years from diagnosis. Follow-up from HDT/ASCT was over 16 years for 153 patients (3rd quartile). The median time from diagnosis to HDT/ASCT was 1.8 years. Two hundred and forty-seven patients (38%) never achieved a complete remission (CR) before HDT/ASCT. Two hundred patients (31%) received HDT/ASCT after achievement of first CR (CR1), 43% of them requiring more than one chemotherapy line to achieve CR1; 26% in 2nd CR, 5% in 3rd CR, 21% in 1st partial response (PR), 12% in chemosensitive recurrence, and 5% with active disease. Of the 321 patients assessable for the FLIPI, 33% had a low-risk (LR), 36% an intermediate-risk (IR), and 45% a high-risk (HR) score; and of the 305 patients assessable for the FLIPI II, 22% had a LR, 38% an IR and 40% a HR. Of the 127 patients in CR1 assessable for the FLIPI, 28% had a LR, 40% an IR, and 32% a HR; of the 115 patient assessable for FLIPI II, 14% had a LR, 46% an IR, and 40 % a HR. One third of patients received Rituximab prior to transplant. Results: Median PFS and OS were 9.4 and 21.3 years, respectively. Patients transplanted in CR1 achieved significantly better final PFS (68%) and OS (73%), than those transplanted in 2nd CR (median PFS 110 months (mo.) and final OS 58%; P <.0005) and the latter ones better than those transplanted in 1st PR (PFS median PFS 31 mo. and median OS 118 mo.; P < .0005) (figure 1). Neither FLIPI1 nor FLIPI2 reached statistical significance in patients transplanted in CR1 (P= .5 and P= .2 for PFS and OS, FLIPI 1 comparisons; P= .47 and P= .1 for PFS and OS, FLIPI 2 comparisons, respectively). Although in the global series patients who received Rituximab prior to HDT/ASCT had a better prognosis than those who did not (median PFS not reached vs median PFS 92 mo, respectively, P= .0005; median OS not reached vs median PFS 246 mo, respectively, P= .0012), treatment with Rituximab has no prognostic impact in cases transplanted in CR1. Only 6 patients died beyond 10 years of follow-up, (1 disease progression, 3 second malignancies, 2 unrelated causes). The accumulated incidence of second malignancies of the global series was 12%. A plateau was observed in the PFS and OS curves for patients transplanted in CR1 beyond 15.9 years from transplantation (figure 1). Conclusions: To the best of our knowledge there is no study on the therapeutic impact in the evolution of LF offering such a long follow-up. HDT/ASCT is a good option of consolidation for those patients who achieve a good quality of response with chemotherapy. The finding of a plateau beyond 15.9 years for patients transplanted in first remission suggests that a significant number of patients from this group may never relapse and could be cured, even those with poor initial features. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The role of complete response in multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (15) ◽  
pp. 3139-3146 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact ◽  
Good Partial Response

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.

scholarly journals Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation By Conventional Microscopy in Multiple Myeloma after High Dose Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3396-3396
Author(s):  
Camille Claracq ◽  
Murielle Roussel ◽  
Benjamin Hébraud ◽  
Michel Attal ◽  
Herve Avet Loiseau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Survival Outcomes ◽  
High Dose ◽  
High Dose Therapy ◽  
Impact On Survival ◽  
Bone Marrow Plasma ◽  
Conventional Microscopy

Abstract Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation by Conventional Microscopy in Multiple Myeloma after High Dose Therapy. Background: The achievement of at least CR is a crucial step for a long-lasting response and prolonged survival after autologous stem cell transplantation (ASCT) in patients (pts) with multiple myeloma (MM). The current definition of complete remission (CR) or better in MM requires a negative serum and urine immunofixation (IF) and <5% bone marrow plasma cells (BMPCs). Additional prognostic tools are related to sFLC ratio, immunophenotypic and molecular evaluations, when possible. As BMPCs levels could differ if evaluated by BM biopsy or aspirate (the latter supposed to underestimate BMPCs count), we aim to determine a new threshold for PCs in BM aspirate and to determine whether it could be, in association with PCs morphology by standard microscopic evaluation, an easy and cheap surrogate marker for outcome, in the absence of sFLC assay and/or phenotypical-molecular analysis for MRD. Material and Methods: 191 de novo MM pts treated between 2003-2010 in Toulouse's myeloma and BMT center with adequate clinical and biological data were retrospectively studied. Responses were evaluated at day 100 after ASCT in all pts according to IMWG criteria. BM examination comprised PCs count, BM cellularity, and the presence of PCs dysmorphy. Progression free survival (PFS) was calculated from the start of therapy until progression, death or last follow-up. Overall survival (OS) was calculated from the start of therapy until death or last follow-up. The Kaplan-Meier method was used to estimate the survival distribution. Results: Baseline demographics and initial disease characteristics are summarized in table 1. Median follow-up is 6 years. At the completion of ASCT, 49 pts (26%) achieved CR, 89 (47%) VGPR and 41 (21%) PR; 57 pts (30%) had a negative serum IF (sIF). Overall, 151 pts relapsed and 68 died with median PFS and OS of 36 and 99 months, respectively. At D100, median PCs count was 1% (range 0-23%): 1% (0-3%) in CR pts, 1% (0-23%) in VGPR pts, and 1.5% (0-7%) in PR pts. Only 1 pt with negative sIF had 5% BMPCs and a positive urine IF, and was assessed as VGPR. Overall, 55 negative sIF pts had 2% or less BMPCs. The number of 2% of BMPCs was found to be predictive, irrespective of response. Median PFS was 39 vs 21 months if BMPCs is > 2% (p<.001) and median OS was 99 months vs 66 (ns). We further aimed to evaluate the impact of PCs dystrophy on survival outcomes in 176 evaluable pts. PCs dysmorphy was reported in 29 pts including 3 pts in CR, 9 VGPR and 13 PR, respectively. All except 2 pts relapsed, with a median PFS of 26 mo (vs 39, p=.002). Nineteen died with a median OS of 60 mo (vs 101, p=.003). For pts at least in VGPR, median PFS was 26 mo in case of PCs dysmorphy vs 40 mo (p=.004) and median OS was 59 mo vs not reached (p=.005). (see figures) Conclusion: conventional microscopy of BM aspirate is a useful and rapid tool to evaluate the percentage of PCs and their morphology as a first step to assess the residual tumor mass in patients with MM after ASCT, and it constitutes a good predictor for disease progression and survival outcome. These findings have to be confirmed and the exact threshold of PCs remains to be determinate in a large prospective study. Table Characteristics n=191 Sex: M/F, n 109/82 Median age, y (range) 57 (31–68) Isotype, n (%) IgG, IgA, LC 123 (64), 35 (18), 28 (15) ISS stage, n (%) n= 158 I, II, III 85 (54), 40 (25), 33 (21) Median bone marrow plasma cells, % (range) 23 (1-96) Median b2-microglobulin, mg/L (range) 3.1 (1.3–19.4) Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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