Evaluation Of Immunoglobulin Variations (Clonal Changes) In Symptomatic Multiple Myeloma (MM) Patients’ Course

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3173-3173
Author(s):  
Eftychia Nikolaou ◽  
Panayiotis Panayiotidis ◽  
Katerina Sarris ◽  
Dimitrios Maltezas ◽  
Efstathios Koulieris ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Median Number ◽  
Immunoglobulin M ◽  
Rank Test ◽  
Clinical Relapse ◽  
Cell Competition ◽  
Number Of Treatment

Abstract Changes in the production of monoclonal intact immunoglobulin (M-Ig) or of serum free light chains (sFLC) during symptomatic MM patients’ relapse eventually reflect molecular myeloma cells changes and / or reveal clonal cell competition. We aimed to study changes in Ig production (CIg) in symptomatic MM patients and to evaluate related frequency and corresponding specific disease characteristics. Patients and Methods 232 symptomatic MM patients with available follow-up sFLC measurements, were retrospectively studied. Light chain escape (LCE) was defined as sFLC increase with stable or falling M-Ig concentrations, M-Ig escape (MCE) as decreasing sFLC with increasing M-Ig, de-differentiation (DD) as clinical relapse with normal or decreased M-Ig and sFLC and Clonal Domination (CD) as normalization of formerly increased IgG, IgA or FLC in relapsing patients presenting increase of another component. Survival was calculated from diagnosis or from CIg date to last follow-up or death, survival curves were plotted by Kaplan-Meyer Method and assessed by the log-rank test. Results There were 94 women and 128 men, median aged 66 years; 29%, 42%, 29% and 22%, 30%, 48% were in Durie-Salmon and ISS stages I, II, III and 1, 2, 3 respectively. MM type was IgG MM in 59%, IgA in 21%, light chain only in 17%, IgD in 2% and non-secretory in1%. Median survival of the whole cohort was 46,4 months. CIg was observed in 39 patients (17%), consisting in LCE in 15 patients (6%), MCE in 7 (3%), DD in 5 (2%) and CD in 10 (4%); two additional patients (1 IgD and 1 LC) transiently produced another monoclonal component that was IgG in both cases, while in stringent complete remission. In CD patients, the dominated clone was IgG in 9 out of 10 patients, while the dominating one was LC in 8 and IgA in 2. LCE and MCE were more frequent in IgG patients. The median number of treatment lines received prior CIg was 5 for LCE, 4 for MCE, 2 for DD and 1 for CD. LCE and MCE patients had all received novel agents and/or ASCT. The median time from CIg to last follow-up or death was 2,6 months (2,2-3) for LCE, 3,3 months (2,2-4,4) for MCE, 6,3 months (1,1-11,6) for DD and 31,1 months (23,6-38,6) for CD. Patients presenting LCE, MCE and DD had a considerably shorter survival after CIg compared to patients presenting CD (p=0,0002). However because CIg was usually a late event in the course of the disease the overall survival of CIg patients was 60,6 months. In conclusion, LCE, MCE and DD are late events in the course of MM, mainly observed in patients whose previous treatments included with novel drugs. They reflect a very aggressive disease behavior with shortened survival thereafter, probably due to the emergence of a new resistant clone. CD was mainly observed in patients secreting low IgG levels and FLCs, and possibly reflect IgG clone remission in biclonal patients, given that thereafter, the disease behaves as a usual multiple myeloma, secreting however the other clone. Disclosures: No relevant conflicts of interest to declare.

Efficacy of Lenalidomide-Based Regimens in Multiple Myeloma Complicated by Extramedullary Plasmacytomas at Relapse or Progression.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4952-4952 ◽  
Author(s):  
Jose Manuel Calvo-Villas ◽  
Adrian Alegre ◽  
Ricarda García-Sánchez ◽  
Miguel T Hernández ◽  
Pilar Giraldo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Bone Lesions ◽  
Complete Disappearance ◽  
Toxicity Profile ◽  
Small Series ◽  
Extramedullary Plasmacytomas

Abstract Abstract 4952 Background Current clinical observations on extramedullary myeloma (EM) are based on small series of relapsed myeloma patients (pts) and, in this situation, results suggest that the disease course is often aggressive. Among novel therapies for extramedullary involvement, thalidomide has provided poor results and bortezomib is emerging as a possible useful drug. The role of lenalidomide for treatment of multiple myeloma (MM) with EM is still under investigation. Aim A multicenter retrospective study was performed by PETHEMA (Spanish Myeloma Group, Spain) to evaluate the response rate and toxicity profile of lenalidomide-based regimens in myeloma patients with extramedullary involvement at relapse or progression. All the cases were evaluated for response of MM and improvement of extramedullary plasmacytoma. Patients and Methods From October 2007 to March 2009, thirteen patients (median age 67 years; range 61–87; 7 females) treated with lenalidomide-containing regimens were recorded. Patients with bone disease without extramedullary manifestations were excluded. Response of MM was evaluated according to the new international criteria and the response of EM by measuring size changes by physical examination, CT scans and/or MR imaging. Adverse events were graded based on the WHO toxicity scale. The M-protein type was IgG in 7 cases, IgA in 5 and light chain in 1. The type of light chain was κ in 7 pts and l in 6. In eight patients the soft-tissue plasmacytomas may have developed from underlying bone lesions [(skull (n=2), rib cage (n=4) and paravertebral (n=2)], two patients had subcutaneous nodules and three had visceral involvement (liver (n=1), lung and kidney (n=1) and pleura (n=1). Multiple localizations were present in 4 pts (30.7%). Six cases (79.6%) received previous antimyeloma treatment for EM before lenalidomide therapy and the incidence of prior bone plasmacytomas was 61.5%. Median time from initial antimyeloma therapy to treatment with lenalidomide was 34 months (range 5 - 115). Median number of prior lines of chemotherapy regimens was 3 (range 1 – 4), including autologous stem cell transplantation in 2 pts, bortezomib-containing regimens in 12 (92.3%) and previous exposure to thalidomide in 1 patient. Ten pts received standard lenalidomide dose (25 mg/day every 4 weeks) plus dexamethasone (40 mg/d PO ranging from 1 to 12 doses/cycle) every 3-week; and three patients received lower doses of lenalidomide and/or different schedules. Involved-field radiotherapy was given in 2 cases. Thirty percent of patients required lenalidomide dose reduction, because of toxicity or intolerance. Results Median duration of lenalidomide treatment was 3.6 months (1 – 15). One case was not evaluable for response because of death from disease progression after one cycle. In nine out of twelve evaluable patients (75%), MM responded to lenalidomide regimens according to EBMT criteria. Three (25%) achieved complete response, five (41.6%) partial response and 1 (8.3%) minimal response. Median time to response was 63 days (range 37 – 180). Regarding EM, nine patients showed response in the size of extramedullary plasmacytomas. Seven (58.3%) achieved complete disappearance of EM and two pts reduction of the size. Response of EM was also achieved in 75% of pts previously exposed to bortezomib, and in 4/9 cases who received therapies for prior extramedullary involvement. Median follow-up period was 6.3 months (1 – 15.8). Median overall survival from the start of lenalidomide therapy was 4.7 months. At the time of analysis, seven patients were still on therapy, and ten (76.9%) were alive. Only one out of the 9 patients who had achieved a response has relapsed so far. Toxicity profile (grade 3/4) was: thrombocytopenia, 4 (30.7%); anemia, 2 (15.3%); neutropenia, 5 (46.4%); neutropenic fever, 1 (7.6%) and others, 3 (11.8%). No deep venous thrombosis (DVT) was reported. Thrombosis prophylaxis was used in most cases (92%) patients. Conclusions We report one of the first investigations specifically evaluating the activity of lenalidomide on EM. Lenalidomide-containing regimens could be an alternative promising approach to achieve clinical response in heavily treated MM patients with extramedullary disease. The duration of response and the best regimen or combination are at present unknown. These preliminary observations require further analysis and longer follow-up. Disclosures No relevant conflicts of interest to declare.

scholarly journals Carfilzomib-Pomalidomide-Dexamethasone (KPD) in Relapsed/Refractory Multiple Myeloma Patients - an Institutional Retrospective Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5572-5572
Author(s):  
Pallavi Mehta ◽  
Neha Yadav ◽  
Mohan Bhaarat ◽  
Sumeet Prakash Mirgh ◽  
Vishvdeep Khushoo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
Haematological Toxicity ◽  
Response Assessment ◽  
Median Number ◽  
Entire Cohort ◽  
Response Status

Introduction Multiple myeloma has relished the emergence of various novel agents in last few decades. Unfortunately,relapses are still an inevitable part and at each relapse, treatment choice becomes a complex decision making process as these patients usually have exhausted conventional therapeutic regimens.Carfilzomib is a second-in class Proteosome Inhibitor (PI) and has been approved for patientsrefractory to minimum 2 lines of prior therapies. We are, hereby, presenting our initial experience with this novel combination (KPD)in RRMM patients at our centre. Methodology Retrospective study of RRMM patients who received KPD therapy from August 2017 till October 2018. Responses were assessed as per International Myeloma Working Group. Study was approved by Institutional Review Board. Results Total 39 patients were treated with KPD regimen during study period. Median age was 56 (32-74 years) with male ratio of 51.2% (n=20). At baseline presentation, bone disease {n=32 (82%)} was the most common presenting complaint followed by anemia {n=21 (53.8%)} and renal failure {n=16 (41%)}. Most common ISS staging was ISS-3 {n=18(46.1%)} and subtype was Light chain myeloma {n=15 (38.3%)} followed by IgG {n=13 (33.3%)}.Fluorescence In Situ Hybridization (FISH) was available in {n= 10 (25%)} and it was positive for del13q (n=1/10) and del17p (n=1/10) and t(11;14) (n=1/10). (Table-1) Median number of prior lines of chemotherapy was 3(1-15). Thirty-six (91%) patients were relapsed/refractory to both bortezomib and lenalidomide whereas n=3(9%) were relapsed/refractory to bortezomib only. Eleven (30.5%) patients underwent SCT pre KPD therapy including 2/11 patients received double SCT. Pre KPD 25 (64.1%) patients had progressive disease (PD), 10 (25%) had relapse and 4 (11.1%) patients had stable disease (SD). Median number of KPD cycles were 3(1-8). Median number of KPD cycles after which response assessment was donewas 3 (2-8). Median time to treatment response was 3 (2-7) months. ORR was 51.2% {CR-n=5 (12.8%); VGPR-n=5 (12.8%), PR-n=10 (25.6%)} whereas 2 (5.1%) patient had SD and 10 (25.6%) patients had PD at 2-8 cycles. Two (5.1%) patients are yet to be assessed. (Table-1) Common hematological toxicities seen were anemia (n=8), thrombocytopenia (n=13){grade-3/4=30.7%; n=4/13} and neutropenia(n=14){grade3/4=21.4%; n=3/14}.Non haematological toxicity such as cardiac toxicity was not observed in our patients. Pre KPD 2D-ECHO was available for 13 patients and which was normal in all patients. Post 2-4 cycles of KPD, 2D-ECHO was available for 7 patients and all patients had normal ECHO. Carfilzomib induced hypertension was seen in 20 patientsand could be well controlled with antihypertensives. Peripheral neuropathy (grade1/2) was seen in 10 patients. We also observedCarfilzomib induced hyponatremia in one patient.Febrile neutropenia(bacterial =6, viral=4, possible fungal=5) was seen in 14 patients.(Table-2) Twelve (20.5%) patients proceeded to either maintenance therapy or autologous stem cell transplantation (ASCT). Eight patients opted only for maintenance (carfilzomib=5, pomalidomide-dexamethasone=2 and pomalidomide =1). Remaining n=4/12(16%) patients received SCT. Pre SCT response status was VGPR n=2; PR n=1 and SD=1. Post SCT response status was VGPR (n=3) &PR (n=1). Post SCT, 3 patients were started on maintenance therapy as Bortezomib/pomalidomide=1, Pomalidomide/dexamethasone=2. One patient has been continued on KPD as a consolidation therapy. At a median follow-up of 10 months (1-14 months), relapse rate was 12.8% (n=5). Ten (25.6%) patients had PD.Mortality rate was 8.3% (n=3), commonest cause being progressive disease. The estimated mean PFS, OS and EFS of entire cohort was 11.9 months (95% C.I. 10.8- 13 months) (figure-1 a), 13 months (95% C.I. 11.9-14 months) (figure-1 b) and 7.9 months (95% C.I. 6.5-9.3 months) (figure - 1 c) respectively. Conclusion KPD is a well-tolerated regimen for patients with RRMM who have exhausted frontline myeloma regimen, however at the cost of significant side effects like infections and hypertension. It seems to be a convincing regimen as a bridge to ASCT but warrants further studies with longer follow-up to validate our results. Disclosures No relevant conflicts of interest to declare.

scholarly journals Managing Multiple Myeloma with Second and Later Lines of Therapy: A Challenge in Developing Countries

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5564-5564
Author(s):  
Venkateswar Rao Pydi ◽  
Stalin Chowdary Bala ◽  
Sadashivudu Gundeti
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Median Number ◽  
Rank Test ◽  
Response Evaluation ◽  
Female Ratio ◽  
Line Therapy ◽  
Best Response ◽  
To Receive

Introduction: Multiple myeloma is characterised by abnormal plasma cell proliferation leading to anaemia, hypercalcemia, skeletal lytic lesions and renal failure. Though myeloma is incurable, novel agents have improved the outcomes. Despite the availability of multiple new agents which lead to improvement in survival, majority of patients are still unable to receive second and further lines of therapy. The present study was designed to analyse the outcomes of patients who received 2nd line and later lines of therapy. Materials and methods: Data of all patients diagnosed with multiple myeloma from 2013-2018 was retrieved. Clinical, haematological, other significant lab parameters, treatment details were noted. For patients who progressed on 1st line therapy and those who had responses of less than PR, 2nd line therapy was started. PFS 2 was calculated from start of 2nd line therapy till progression. Survival probabilities were estimated by Kaplan-Meier method and compared by log rank test. SPSS 25 software was used for statistical analysis. Results: A total of 258 patients were diagnosed between 2013 and 2018. The median age at presentation was 56 years (range, 28-84 years). Male to female ratio was 2.03:1. Of these 258 patients, 191(74%) patients took planned therapy and 172(66%) patients had at least one response evaluation. Of these, only 81(47%) patients were able to receive 2nd line therapy. Five patients died during therapy, 16 patients did not complete planned therapy and 58(33%) patients had response evaluation. Seventy five percent of patients received triplet chemotherapy. MPT and VRD were the most commonly used regimens. Median number of cycles before response evaluation was 4 cycles. Of these 81 patients, 14(17.2%) patients underwent autologous stem cell transplantation. The baseline characteristics and outcomes were shown in Table 1. Twenty (34%) patients received 3rd line and further lines of therapy. Of these 20 patients, best response was VGPR, seen in 50% percent of patients. The median progression free survival (PFS2) was 15 months (range1-59 months). At a median follow up of 18 months, 2-year PFS was 61.6%. The 2-year OS of all patients and those who receive 2nd and later lines were 76% and 84% respectively. Conclusion: Only 30% of patients received second line and one tenth of all patients were able to receive third and later lines of therapy. Majority of the patients who received second and later lines of therapy had ≥ VGPR. Overall survival was higher in patients who received further therapy at progression. Outcomes in multiple myeloma can be improved by optimal sequencing of available drugs. Treatment discontinuity is major caveat in management of myeloma in real-world scenario and overcoming this challenge might improve survivals. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic Value of Circulating Plasma Cells in Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1808-1808
Author(s):  
Lijuan Chen ◽  
Jianyong Li
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
High Risk ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
High Risk Group ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Therapeutic Approaches

Multiple myeloma (MM) is biologically diverse and there is a significant variation in survival time from a few months to several years. The presence of circulating plasma cells (CPCs) is associated with a worse prognosis in patients with MM. This study retrospectively analyzed CPCs by 8-color multi-parameter flow cytometry in 108 cases of newly diagnosed MM patients to investigate its value for outcome prediction. Among them, 58 (53.7%) patients were CPCs positive expression. The optimum cutoff predicting for overall survival was determined as 0.29% by using a ROC analysis. Compared with patients with CPCs < 0.29% (n = 75, 69.4%), those with CPCs ≥0.29% (n = 33, 30.6%) showed lower Erythrocyte sedimentation rate(ESR) (P = 0.0032), but higher lactate dehydrogenase (LDH), ferritin (FER) , BM PCs and P53 deletion in BM by FISH (P = 0.001, 0.003, 0.014, and 0.001,respectively). With the median follow-up time 17 months (range, 2.0-37.0), the median PFS in the subgroups with CPCs<0.29% and ≥0.29% was not reached and17.0 months (95% confidence interval (CI):14.85-19.15), respectively, and the median OS was not reached and 12.5months (95% CI: 6.35-18.65), respectively. On multivariate analysis for OS, factors independently predictive of mortality were CPCs≥0.29% (hazard ratio (HR) 4.172; 95% CI, 1.61-10.79; P=0.003), Deletion P53(HR 11.54; 95% CI, 4.06-32.84; P<0.001). We further developed a convenient two-factor risk stratification based on CPCs and p53 deletion according to the results of log-rank test, univariate and multivariate analysis. The high-risk group was defined as both CPCs ≥ 0.29% and P53 deletion, accounting for 10% of the population, have a dire prognosis (median PFS = 5 months; OS = 10 months) despite modern therapies .These results identified CPCs as an unfavorable prediction for the outcome of MM. A combination of p53 deletion may screen out a high-risk subgroup which should be considered for novel therapeutic approaches. Disclosures No relevant conflicts of interest to declare.

Nonmyeloablative Allogeneic HCT From Unrelated Donors for Multiple Myeloma (MM).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3391-3391
Author(s):  
Marcello Rotta ◽  
Barry E Storer ◽  
Thoralf Lange ◽  
Michael Pulsipher ◽  
Judith Shizuru ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Remission ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Median Number ◽  
High Dose ◽  
Unrelated Donor ◽  
Allogeneic Hct ◽  
Unrelated Donors

Abstract Abstract 3391 Poster Board III-279 BACKGROUND: We previously reported on the outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in 24 patients (pts) with poor-risk multiple myeloma treated by Seattle Consortium Centers (Georges et al BBMT 2007). Here we update our observation to 43 pts with a median follow up of 3.3 years after allografting. PATIENTS: Pts with stage II-III MM (n=43) received AlloHCT at 9 centers between May 2000 and September 2008. Forty pts (93%) were matched with their donors for 10 of 10 HLA alleles, and 3 (7%) had single HLA-C allele-level mismatches. Median age at allotransplant was 53 (range 35–67) years. Median number of prior treatments was 2 (1–3), and median number of prior treatment cycles was 8 (5–22). All pts but 2 received at least 1 (range 1-3) high dose-Autograft regimen. Fifteen pts (35%) received planned tandem Auto/AlloHCT as consolidation to first line therapy. Allogeneic conditioning was with 2 Gy TBI plus fludarabine 90 mg/m2 and post allografting immunosuppression was with mycophenolate mofetil (MMF) and cyclosporine or tacrolimus. Disease status at allogeneic HCT included complete remission (CR, 6 pts, 14%), very good partial remission (VGPR, 12 pts, 28%), partial remission (PR, 14 pts, 33%) and refractory disease (RD, 11 pts, 26%). RESULTS: All pts had sustained donor engraftment. Twenty-eight (65%) developed grade 2 to 4 acute graft-versus-host-disease (GVHD) and 6 pts (14%) developed 3 to 4 acute GVHD. Twenty-six pts (60%) had extensive chronic GVHD. The overall response rate was 86%, with 18 pts (42%) achieving CR, 14 (33%) VGPR and 5 (12%) PR. With a median follow-up of 3.3 (0.3–8.1) years from allografting, median time to progression was 1.1 years. Median overall survival (OS) has not been reached. Median progression-free survival (PFS) was 1.5 years. Five-year estimated OS and PFS were 51% and 21% respectively. Cumulative incidence of nonrelapse mortality (NRM) at 100 days, 1 and 5 years were 2%, 16% and 19% respectively. The subgroup of 15 pts receiving upfront tandem Auto/AlloHCT had five-year estimated OS and PFS of 72% and 37%, respectively. These results are similar to the outcomes we observed in a series of 102 patients with MM who received upfront tandem Auto/AlloHCT from HLA-identical sibling donor (Rotta et al, Blood 2009) where five-year OS and PFS were 64% and 36%, respectively. CONCLUSION: The use of unrelated donors leads to sustained donor engraftment and is associated with a low 1-year NRM (16%). As consolidation of first remission, Tandem Auto/Allo HCT leads to similar 5-year outcomes as HCT from HLA-identical sibling donors. Disclosures: No relevant conflicts of interest to declare.

Association Between Immunoparesis and a Skewed Free Light Chain (FLC) Ratio: A New Prognostic Factor Of Progression from MGUS To Multiple Myeloma?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5314-5314
Author(s):  
Michele Pizzuti ◽  
Alberto Santagostino ◽  
Giuseppina Smaldore ◽  
Ida Chitarrelli ◽  
Domenico Vertone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Light Chains ◽  
Molecular Events ◽  
Risk Of Progression ◽  
Two Parameters

Abstract Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3% of people older than 50 years and up to 10% in those older than 70; it is associated with a 1%/year risk of progression to Multiple Myeloma (MM). In recent years there have been improvements in risk stratification models (involving molecular markers) of this disorder, which have led to better understanding of the biology and probability of progression of MGUS. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. Free Lights Chains (FLC) ratio, plasma cells immunophenotype and DNA aneuplody are now important parameters of progression, in addition to the already known prognostic factors (immunoparesis, type and amount of the monoclonal component (MC). Recent data report immunoparesis and a skewed FLC ratio in 25% and 30%, respectively, of patients (pts) at diagnosis. In this study we evaluated the incidence of these two parameters in a cohort of 114 pts with MGUS, if they are associated and if their incidence is influenced by other parameters (time from diagnosis, type of Immunoglobulin (Ig) and/or light chains). The patients screened were 56 males and 58 females with a median age of 67 years (45-91). Median time from diagnosis to the time of observation was 3 years (0-21). The MC was IgA in 13 pts, IgG in 88, IgM in 13; 74 had a clonal Kappa (K) and 40 a lambda (L) light chain. K/L ratio was abnormal in 57 pts (50%). Immunoparesis was present in 60 pts (52,6%): 22 with a normal K/L ratio (38,5%) and 38 with an abnormal K/L ratio (66,6%) (p-0.004). In 18 pts two classes of Ig were involved. An association between the two parameters occurred in 39 pts (34,2%); it was more frequent in IgA MGUS (61,5%) than in IgG (31,8%) and IgM (23%); we did not observe any differences about immunoparesis between K MGUS (33,7%) and L MGUS (32,5%). The association between a skewed K/L ratio and immunoparesis was present in 25.4% of pts with time from diagnosis of less than 3 years and in 48,8% of pts with a longer time from diagnosis (p-0.04). Our new data confirm that immunoparesis is more frequent in pts with an abnormal K/L ratio. The association seems to be more frequent in case of IgA gammopathy; there are no differences between the two types of light chain. Our data also confirm that the longer is the time elapsed from diagnosis, the higher are the frequency of an abnormal K/L ratio and the incidence of immunoparesis, with a greater probability of association. We need still a larger number of pts with an adequate follow up to evaluate if the association between immunoparesis and abnormal K/L ratio has a prognostic value, although the higher frequency of association in the subset of pts with a longer time from diagnosis seems to contradict this hypothesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain

2021 ◽  
Vol 11 ◽  
Author(s):  
Angel P. Sempere ◽  
Leticia Berenguer-Ruiz ◽  
Ines Borrego-Soriano ◽  
Amparo Burgos-San Jose ◽  
Luis Concepcion-Aramendia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Real World ◽  
Median Number ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Clinical Practice Setting ◽  
Number Of Treatment ◽  
Relapsing Multiple Sclerosis

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting.Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded.Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4–6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P &lt; 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious.Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

Improving Outcomes in Patients with Renal Failure Secondary to Multiple Myeloma: Results From ChAR2M2.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1875-1875
Author(s):  
Colin Hutchison ◽  
Parisa Airia ◽  
Mark Cook ◽  
Daniel Grima
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Side Effects ◽  
Light Chain ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Treatment Patterns ◽  
Free Light Chain ◽  
High Rate ◽  
Sustained Reduction

Abstract Abstract 1875 Poster Board I-900 Study purpose: To explore how free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) has been adopted into clinical practice for the management of renal failure secondary to multiple myeloma. Describing treatment patterns and the laboratory and clinical outcomes associated with its use. Methods: A chart audit of patients treated with FLC removal by HCO-HD, using the Gambro HCO 1100 dialyser, was performed in 16 dialysis centers across 9 countries. Patient demographics, treatment patterns and dialysis side-effects were recorded. In addition, the following outcomes were measured: dialysis independence and reductions in serum FLCs concentrations at 12 and 21 days. Results: Data for 66 patients was entered. Patients had an average age of 65.1 (SD×10.1); 42 of them (63.64%) were male and 24 (36.36%) were female. Sixteen (24%) presented with relapsing myeloma and 50 (76%) had de novo disease. On average, each patient received 13 HCO-HD sessions (SD×8). Forty-one patients became dialysis independent (62.12%), after an average of 12 sessions. Dialysis related side-effects were reported in 6% of all patients. Forty patients (60.61%) were reported to have a sustained reduction in serum FLC concentrations by day 12. By day 21 this had increased to forty-one (62.12%). Among the patients who achieved a sustained reduction in serum FLC concentrations, 28 (70%) had a decline in FLC levels of more than 50% by day 12 and 34 (82.93%) by day 21. Among patients who achieved sustained reduction of more than 50% in serum FLC concentrations by day 12, 75% became dialysis independent. In comparison only 53% of those with a reduction of less than 50% became dialysis independent (p×0.007). Furthermore, among patients who achieved sustained FLC reduction of greater than 75%, 81% became dialysis independent. The rate of dialysis independence was also significantly higher in patients with de novo disease compared with those with relapsing myeloma (64% versus 56%, p×0.04). Conclusion: Free light chain removal by HCO-HD was well tolerated and associated with a very high rate of dialysis independence in patients with renal failure secondary to multiple myeloma. Rates of renal recovery were greater in patients with de novo myeloma and those who achieved an early reduction in serum FLC concentrations. Disclosures: No relevant conflicts of interest to declare.

Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2959-2959
Author(s):  
Daisuke Ohgiya ◽  
Makoto Onizuka ◽  
Hiromichi Matsushita ◽  
Naoya Nakamura ◽  
Hiroshi Kawada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Chemotherapy Resistance ◽  
Nuclear Body ◽  
Rank Test ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2959 Background: Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods: Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results: The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion: Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. Disclosures: No relevant conflicts of interest to declare.

A Phase II Study of Decitabine In Advanced Chronic Myelomonocytic Leukemia (CMML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1873-1873
Author(s):  
Thorsten Braun ◽  
Nathalie Droin ◽  
Benoit de Renzis ◽  
Francois Dreyfus ◽  
Kamel Laribi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Conflicts Of Interest ◽  
Cytogenetic Response ◽  
Median Number ◽  
Costal Margin ◽  
Monocyte Count ◽  
Blood Monocytes ◽  
Grade 3 ◽  
Wbc Count

Abstract Abstract 1873 Background: CMML, now classified among MDS/MPN, is prognostically heterogeneous. We (JCO 1988 6:1417, Blood 1996 88:2480) and others found prognosis in CMML to depend on both “MDS factors” (% marrow blasts, cytopenias, karyotype) and “MPN” factors, ie splenomegaly (SMG), WBC count, extramedullary disease (EMD). Treatment of advanced CMML is difficult. The hypomethylating agents Azacitidine and Decitabine (DAC) have shown efficacy in CMML, but in prognostically heterogeneous cohorts. We conducted a phase II trial of DAC in a well defined cohort of advanced CMML. Methods: To be included, CMML (according to WHO) should have: if WBC<13G/l an IPSS≥1.5; if WBC≥13G/l, two of the following criteria: marrow blasts≥5%, Hb<10g/dl, plts<100G/l, abnormal cytogenetics, SMG >5cm below costal margin, (SMG>5cm), EMD, based on our previous prognostic factors. Pts received DAC 20mg/m2/d IV for 5 days every 28 days for at least 3 cycles. Response criteria were based on IWG 2006 for pts with WBC <13G/L and for pts with WBC > 13 G/L also included evolution of WBC, SMG and EMD (Blood 1996 88:2480). Results: Between Nov 2008 and June 2009, 41 pts were included in 16 centers, of whom 39 completed at least one cycle and were considered evaluable for response (the 2 other pts died from septic shock before and during the first cycle respectively). Median number of cycles was 9 (range 1–17). Median age was 71 years (range 54–88), M/F:30/9. Seventeen pts had CMML 1 and 22 had CMML 2 (including pts with up to 29% marrow blasts). Median WBC count was 29.5G/l (range 4.1–147.3), median blood monocytes 3G/l (range 1.05–95.7), and median BM blasts 10% (1-29). Nine pts had WBC<13G/l and 30 WBC≥13G/l. Abnormal karyotype was found in 18 (46.2%) pts, including +8 and -7 in 7 and 1 case, respectively. 15 pts (38.6%) had SMG>5cm and 8 (20.5%) EMD involving skin (n=5) and lymph nodes (n=3). Overall Response Rate (ORR,) was 38.6% with 4 (10.3%) CR, 8 (20.5%) marrow CR and 3 (7.7%) Stable Disease (SD) with HI. 1 CR pt received allo SCT. 18 (46%) pts had SD without HI and 6 (15.4%) pts progressed to AML. 8 (36.4%) of the 22 RBC transfused pts became RBC transfusion independent. 3/10 (30%) pts with plt<50G/l reached plt>100G/l. Four pts had cytogenetic response (3 CR and 1 PR) exclusively among pts with +8. Median peripheral monocyte count decreased from 4.8G/l to 0.3G/l after 3 cycles of DAC among responders. SMG disappeared in 6/15 (40%) pts and EMD in 6/8 (75%) pts. 16 pts were receiving Hydroxyurea (HY) at inclusion which could be stopped in 12 of them. With a median follow up of 10 months (1-18), 7 pts had died from progression (n=3), sepsis (n=3) and unrelated cause (n=1). Overall Survival (OS) estimate was 60% at 2 years (median not reached). By comparison, in our previous trial of HY in CMML where inclusion criteria were the same, 2 year survival was 43% (median OS 20 months; Blood 1996 88:2480), for a median follow up of 11 months (range1-43). The only factor associated with response to DAC was WHO subtype, CMML 2 pts showing significantly better ORR (30.8% vs 7.7% in CMML 1; p=0.041).There was no difference in survival between CMML 1 and 2 pts. Treatment with DAC was generally well tolerated with, except for usual grade 3/4 cytopenias, and grade 3 fatigue (n=1). Conclusion: DAC is active in advanced CMML and safe in these elderly pts. A possibly better survival than with HY will have to be confirmed in randomized trials. Correlative genetic studies identifying markers potentially predicting response and survival for DAC are currently underway in our lab. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document