Paraprotein levels in assessing effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19511-e19511
Author(s):  
Irina B. Lysenko ◽  
Nailya Guskova ◽  
Oleg Ivanovich Kit ◽  
Natalya Dmitrievna Ushakova ◽  
Nadezhda Golomeeva ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Exchange ◽  
Treatment Effect ◽  
Reduction Rate ◽  
Main Group ◽  
Response To Treatment ◽  
Light Chains ◽  
Control Group ◽  
Blood Levels

e19511 Background: Our purpose was to analyze levels and types of paraprotein in polychemotherapy combined with selective plasma exchange in patients with multiple myeloma. Methods: Blood levels of paraprotein (PP) were studied by capillary electrophoresis (Helena Bioscience V8), and content of plasma cells was determined in the bone marrow of 16 patients (main group) with multiple myeloma (MM) during polychemotherapy (PCT) plus selective plasma exchange (SPE). 14 patients receiving standard PCT were the controls. Results: MM patients in both groups were characterized with the presence of PP in the blood serum with the M-peak in the gamma-globulin zone. Only heavy IgG chains were found, bound to lambda (λ) light chains in 48% and to cappa (κ) light chains in 57.15%. The initial PP level in MM-IgGλ was 91.01±0.79 g/L and was 2.4 times higher than in MM-IgGκ (38.3±0.34 g/L). Significant differences in were found in PP reduction rate and intensity depending on the treatment. PP in the main group reduced by 42.4% after course1, by 41.4% after course 2, by 52.2% after course 3 and by 24% after course 4; in the control group – by 17.2%, 19.3%, 27.9% and 47.3%, respectively. PP levels decreased by 87.4% and 74.6% by the end of the treatment, respectively. The data were confirmed by a decrease in plasma cell content in the bone marrow of patients: up to 1.2% in the main group and 6.2% in the controls. Response to treatment in the main group was registered at the early stages of therapy, and at the late stages in the control group. Treatment effect was associated with the type of secreted PP. In MM-IgGκ, PP levels in the main group decreased by 59.7% after course 1, by 40.6% more after course 2 and by 51.9% after course 3; in MM-IgGλ – by 25.1%, 42.1% and 52.5%, respectively. Treatment effect was noted earlier and PP reduction was more intensive in MM-IgGκ than in MM-IgGλ. PP levels decreased by the end of the treatment by 85.4% in MM-IgGκ and by 73% in MM-IgGλ. Similar changes were observed in the control group. Conclusions: Increased rates and intensiveness of paraprotein reduction reflect effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma. Patients with MM-IgGκ are more sensitive to the therapy.

scholarly journals Evaluation of the Effect of Shenmai Injection on Chemotherapy Efficacy and Side Effects of Acute Leukemia

2019 ◽  
Vol 3 (6) ◽  
Author(s):  
Jianling Qiao ◽  
Xuan Kan ◽  
Fei Qin
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Acute Leukemia ◽  
Control Group ◽  
Blood Levels ◽  
Observation Group ◽  
Impaired Liver Function ◽  
Shenmai Injection ◽  
Before And After ◽  
Bone Marrow Blood

Objective: To study the effect of Shenmai injection on the efficacy and side effects of chemotherapy in acute leukemia. Methods: Sixty-two patients with acute leukemia admitted to the hospital between February 2018 and June 2019 were enrolled in this study. All patients were divided into observation and control groups according to different treatment methods in chemotherapy. The control group was treated with chemotherapy alone. The observation group was treated Shenmai injection combined with chemotherapy. The treatment effect of the two groups was compared, and the incidence of bone marrow blood and side effects before and after treatment were compared. Results: The therapeutic effect of the observation group was 93.55% which was much higher than that of the control group of 74.19%, P<0.05. The bone marrow blood levels of WBC, PLT and Hb in the observation group before and after treatment were 23.97±3.05, 6.76±1.27, 69.01±8.15, 66.96±9.46, 91.07±8.15, 89.35±7.46, respectively, compared with the control group. The difference in the situation after treatment was found to be significant. The incidence of toxic side effects such as nausea and vomiting, impaired liver function and renal dysfunction in the observation group was 9.68%, which was lower than that of the control group (32.26%, P<0.05). Conclusion: Shemai injection has significant effects on the efficacy and side effects of chemotherapy in acute leukemia and effectively improves the effect of chemotherapy.

scholarly journals Chronic lymphocytic leukemia (CLL) terminating in multiple myeloma: report of two cases

Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 532-536 ◽  
Author(s):  
RH Kough ◽  
AZ Makary
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Plasma Cells ◽  
Medical Center ◽  
White Male ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
White Female ◽  
Pathologic Fractures

Abstract Two cases of multiple myeloma (MM) developed late in the course of chronic lymphocytic leukemia (CLL). An 81-yr-old white female developed, after 6 yr of CLL, IgAk MM with sheets of plasma cells abutting sheets of lymphocytes in the bone marrow, multiple pathologic fractures, and 0.26 g/24 free k light chains in the urine. A 74-yr-old white male developed, after 16 yr of CLL, k light chain MM with 20% plasma cells in the bone marrow, multiple panthologic fractures, and 3.7 g/24 hr free k light chains in the urine. In both cases the CLL had responded well to intermittent low-dose chlorambucil therapy, but the MM failed to respond to cyclic melphalanprednisone therapy. A review of 105 cases of CLL seen at the Geisinger Medical Center failed to turn up any other cases of MM developing during the course of CLL. The suggestion that there is an increased prevalence of MM in CLL is an attractive one because both diseases are B cell neoplasms and because of the increased frequency of asymptomatic monoclonal gammopathies in CLL found by others.

scholarly journals Whole-Body Functional MRI and PET/MRI in Multiple Myeloma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3155
Author(s):  
Sébastien Mulé ◽  
Edouard Reizine ◽  
Paul Blanc-Durand ◽  
Laurence Baranes ◽  
Pierre Zerbib ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Functional Mri ◽  
Bone Marrow Involvement ◽  
High Sensitivity ◽  
Response To Treatment ◽  
Whole Body ◽  
Response Evaluation ◽  
Whole Body Mri ◽  
Dce Mri

Bone disease is one of the major features of multiple myeloma (MM), and imaging has a pivotal role in both diagnosis and follow-up. Whole-body magnetic resonance imaging (MRI) is recognized as the gold standard for the detection of bone marrow involvement, owing to its high sensitivity. The use of functional MRI sequences further improved the performances of whole-body MRI in the setting of MM. Whole-body diffusion-weighted (DW) MRI is the most attractive functional technique and its systematic implementation in general clinical practice is now recommended by the International Myeloma Working Group. Whole-body dynamic contrast-enhanced (DCE) MRI might provide further information on lesions vascularity and help evaluate response to treatment. Whole Body PET/MRI is an emerging hybrid imaging technique that offers the opportunity to combine information on morphology, fat content of bone marrow, bone marrow cellularity and vascularization, and metabolic activity. Whole-body PET/MRI allows a one-stop-shop examination, including the most sensitive technique for detecting bone marrow involvement, and the most recognized technique for treatment response evaluation. This review aims at providing an overview on the value of whole-body MRI, including DW and DCE MRI, and combined whole-body 18F-FDG PET/MRI in diagnosis, staging, and response evaluation in patients with MM.

Personalized Treatment with low doses of Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma in frail or Elderly Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5049-5049
Author(s):  
Angel Ruedas ◽  
Pablo Guisado ◽  
Beatriz Aguado ◽  
Ricardo Perez ◽  
Joaquin Martinez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Elderly Patients ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Light Chains ◽  
Bone Marrow Toxicity ◽  
Low Doses ◽  
Very Elderly

Abstract Abstract 5049 Background. Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims. To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods. The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results. 38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions. Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures: No relevant conflicts of interest to declare.

Soluble Bcma in Myeloma Serum Binds Its Ligands BAFF and Prevents Normal Antibody Production in Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1799-1799
Author(s):  
Eric Sanchez ◽  
Abigail Gillespie ◽  
Nika Manik Harutyunyan ◽  
George Tang ◽  
Jillian Gottlieb ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Antibody Production ◽  
Conflicts Of Interest ◽  
Scid Mice ◽  
Response To Treatment ◽  
Control Group ◽  
Raji Cells

Abstract Introduction: A hallmark of multiple myeloma (MM) is the low levels of uninvolved immunoglobulin (Ig) levels. B-cell maturation antigen (BCMA) is a receptor expressed in mature non-malignant and malignant B lymphocytes, including plasma cells. Its ligands are B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL). We previously demonstrated that BCMA is present in the serum of MM patients (pts) and that its levels predict survival (Sanchez et al. Br J Haematol 2012). We hypothesized that circulating BCMA binds it ligands, preventing normal plasma cell development in MM patients which may explain their reduction in uninvolved Ig levels. Methods: BCMA-Fc and control Ig were obtained and reconstituted in PBS (R&D Systems). Retro-orbital bleeds were performed on C57 Bl/6 and SCID mice implanted with the human MM xenografts LAGλ-1, LAGk-1A or LAGk-2. Human BCMA and mouse BAFF, IgM, IgA and IgG levels were measured with ELISA (R&D Systems & Bethyl Laboratories). The Raji B-cell line was obtained from the American Type Culture Collection (Rockville, MD, USA). Human IgA and IgG levels were determined in MM patients using nephelometry (Immage 800, Beckman Coulter). Hevylite® Assays (Binding Site) were used to quantify the levels of heavy-light chain isoform pairs in MM patients. Results: We determined if mBAFF formed complexes with human BCMA (hBCMA) in the plasma from SCID mice implanted with LAGλ-1, LAGκ-2 or LAGκ-1A, and were able to identify mBAFF-hBCMA complexes in plasma samples from these mice. To determine what effect human BCMA had on Ig levels in immune competent mice, rhBCMA-Fc or control Ig-Fc (100 mg) was injected into C57 Bl/6 mice, and plasma IgA, IgM and IgG levels were measured. Decreases in IgA levels were observed following BCMA treatment when compared to baseline plasma IgA on days 4 and 6 (P = 0.0031 and P = 0.0064, respectively), and the control group (P = 0.0087 and P = 0.0221). Samples were also analyzed for mouse IgM levels with similar marked reductions when compared to the untreated (P = 0.0001) and Ig-Fc (P = 0.0088) groups. For plasma IgG levels, a marked decrease was observed on day 6 following rhBCMA-Fc administration when compared to its baseline levels (P = 0.0023), and also when compared to the Ig-Fc control protein (P = 0.0014) and the untreated control (P = 0.0129) groups. We then set out to determine if sera from MM patients contained BCMA-BAFF complexes, using ELISA plates coated with an anti-human BAFF antibody followed by exposure to a polyclonal anti-human BCMA antibody. A strong absorbance indicating the presence of BCMA-BAFF complexes was detected in serum samples from MM patients, whereas no antibody cross reactivity was observed in control samples. We also determined whether human MM serum or rhBCMA-Fc blocked BAFF from binding to Raji B-cells. Raji cells (B-cell line) were incubated with serum from a MM patient containing hBCMA (0.75μg/ml) or rhBCMA-Fc (3 μg/ml) in the presence of rhBAFF (500 ng/ml). Myeloma serum and rhBCMA-Fc decreased rhBAFF binding to Raji cells by 71% (from 96.8 to 25.6 %) and 74% (from 96.8 to 22.9 %), respectively. Next, we determined whether serum BCMA levels inversely correlated with uninvolved Ig levels in MM pts. For pts with IgA (n = 134) or IgG (n = 313) MM, higher BCMA levels (> 100 ng/ml) correlated with below normal levels of uninvolved IgG in IgA MM and uninvolved IgA in IgG MM, whereas lower BCMA levels (< 100 ng/ml) correlated with normal uninvolved levels (P < 0.0001). Using the Hevylite Assay, similar results were observed for the levels of BCMA compared to uninvolved IgG isoforms in both pts with involved IgG lambda (n = 62, P = 0.0006) and IgG kappa (n = 117, P < 0.0001) MM. Conclusions: Our laboratory previously has reported that serum levels of BCMA are increased in the serum of MM patients, and correlates with response to treatment and predicts survival. We now demonstrate 1) the formation of complexes of BCMA with its B-cell ligand BAFF in the plasma of MM xenografts and sera of MM patients, 2) show that rhBCMA and MM patient serum blocks the binding of BAFF to human B-cells, 3) administration of rhBCMA to normal mice results in marked reductions in their antibody levels, and 4) show that BCMA levels inversely correlate with uninvolved Ig levels in MM pts. Thus, the lack of normal antibody production in MM pts results, in part, from circulating BCMA binding its ligands, preventing production of normal antibody-producing cells. Disclosures No relevant conflicts of interest to declare.

Pure Red Cell Aplasia after ABO-Mismatched Allogeneic Stem Cell Transplantation Treated with Therapeutic Plasma Exchange and Rituximab

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5453-5453
Author(s):  
Rebecca Karp ◽  
Jon E. Arnason ◽  
Jacalyn Rosenblatt ◽  
David Avigan ◽  
Robin Joyce ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Plasma Exchange ◽  
Patient Characteristics ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Transfusion Independence ◽  
Cell Engraftment ◽  
Reduced Intensity

Abstract Introduction Pure red cell aplasia (PRCA) is a severe consequence of major and bi-directional ABO-mismatched allogeneic stem cell transplantation (allo-SCT), likely the result of persistent isoagglutinin-producing host plasma cells that have escaped pre-transplant conditioning or graft vs. plasma cell effect (Aung et. al. 2013). PRCA, defined as anemia with reduced reticuloytosis and absence of red cell precursors in the bone marrow at 60 days after transplantation, complicates about 10-20% of all ABO-mismatched allo-SCTs; however, optimal treatment remains unknown. We report 5 cases from our institution of ABO mismatched allo-SCT complicated by PRCA treated with therapeutic plasma exchange (PEX) with or without the anti-CD20 monoclonal antibody rituximab. Report Patient characteristics are shown in Table 1. Indications for transplantation included refractory multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome (table 1); four of five patients underwent myeloablative conditioning, and the fifth received a reduced-intensity regimen due to age and co-morbidities. Prophylaxis for graft-versus-host disease consisted of cyclosporine alone, cyclosporine and prednisone, or tacrolimus and prednisone. ABO mismatching was major in four patients and bi-directional in one patient; all donors and recipients were Rh(D) positive. In all five patients, neutrophil engraftment occurred between days 11-15 after transplantation, with failure of red cell engraftment by day 60. Response Intervention included PEX in all patients, performed every-other-day (table 1). Three patients also received adjuvant rituximab in addition to PEX. Resolution of PRCA, which we defined as transfusion independence, presence of erythroid precursors on bone marrow biopsy, and Òmixed fieldÓ on blood type crossing, occurred in four out of five patients (mean 95 days). In two patients (patients 3 and 5) PEX and rituximab led to transfusion independence in less than 30 days after initiation of PEX. In one patient (patient 2), red cell engraftment occurred 87 days after initiation of PEX; another patient (patient 4) required 10 sessions of PEX and 2 cycles of rituximab (4 weekly doses separated by 6 months) to achieve transfusion independence 253 days after initiation of PEX. One patient (patient 1) had persistent PRCA despite 10 sessions of PEX and died of disease relapse 398 days after transplantation. In one patient (patient 2), tapering of immunosuppression was attempted in conjunction with PEX and led to resolution of PRCA; in the other four, withdrawal of immunosuppression was either not clinically indicated or unsuccessful in resolving PRCA. Conclusion We report five cases of PRCA after ABO-mismatched allo-SCT in the setting of major or bi-directional ABO incompatibility treated with PEX with or without rituximab, with four out of five patients responding to this intervention. This case series demonstrates the potential efficacy of PEX and rituximab for the treatment of PRCA. However, the optimal number of sessions of PEX, timing of this intervention, dosing and schedule of rituximab, and appropriate patient selection still remain unknown. A prospective study is planned. Table 1. Patient characteristics and treatment outcomes Patient Age Disease Graft Conditioning Recipient/Donor ANC>500 Treatment Outcome/TTE 1 48M IgG MM PB MURD MyeloablativeBu/Cy O+/A+ F D+15 PEX 10 sessions PRCA unresolved Died 398 days after transplant of recurrent disease 2 56 M MDS PB MURD MyeloablativeFlu/Bu/ATG O+/B+ M D+11 PEX 10 sessions Withdrawal of immunosuppression Resolution of PRCA 87 days 3 58 M AML PB MRD MyeloablativeFlu/Bu O+/A+ M D+13 PEX 10 sessions Rituximab 2 doses Resolution of PRCA 13 days 4 49 M AML PB MRD MyeloablativeBu/Cy B+/A+ F D+11 PEX 10 sessions Rituximab 8 doses (2 cycles of 4 weekly doses separated by 6 months) Resolution of PRCA 253 days 5 70 M MDS PB MRD RIC Flu/Bu O+/A+ M D+15 PEX 7 sessions Rituximab 4 doses Resolution of PRCA 15 days M: male; MM: multiple myeloma; MDS: myelodysplastic syndrome; AML: acute myelogenous leukemia PB: peripheral blood; MRD: matched related donor; MURD: matched unrelated donor; Bu: busulfan; Cy: cyclophosphamide; Flu: fludarabine; RIC: reduced intensity conditioning regimen; F: female; ANC: absolute neutrophil count; PEX: plasma exchange; TTE: time to red cell engraftment after PEX. Disclosures No relevant conflicts of interest to declare.

scholarly journals Incidental discovery of multiple myeloma, presenting as an amyloid tumor with plasmacytic elements of the thoracic wall

2015 ◽  
Vol 53 (3) ◽  
pp. 267-272
Author(s):  
Oana Şerban ◽  
A. Achim ◽  
Laura Irina Poantă
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Serum Proteins ◽  
Histopathological Examination ◽  
Bone Marrow Aspiration ◽  
Thoracic Wall ◽  
Light Chains ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Contrast Enhanced Ct

AbstractMultiple myeloma is characterized by monoclonal proliferation of bone marrow plasma cells causing multiple bone lesions and overproduction of a monoclonal protein (M-protein) that could deposit in tissues (amyloidosis). Dissemination of the multiple myeloma outside the bone is rare.We present a case of a 76 years old woman presenting with dry cough. Chest X-ray showed a giant tumor of the upper right lung. Contrast enhanced CT revealed a tumor that most probably originated from the structures of the thoracic wall. The transthoracic biopsy was inconclusive. The tumor was resected and the histopathological examination showed amyloid tumor of the thoracic wall with plasmacytic elements and lambda light chains deposits. A bone marrow aspiration was performed that found diffuse plasmacytic infiltrate of 20-60% and the serum proteins electrophoresis with immunofixation revealed elevated IgA and lambda light chains. The patient was diagnosed with IgA and lambda light chains multiple myeloma with consequent AL amyloidosis presenting as thoracic mass.

scholarly journals Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

2021 ◽  
Author(s):  
Meera Mohan ◽  
Samantha Kendrick ◽  
Aniko Szabo ◽  
Naveen K Yarlagadda ◽  
Dinesh Atwal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Clinical Relapse ◽  
Landmark Analyses ◽  
Minimal Residual

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next generation flow cytometry (sensitivity of 10-5 cells) at 3 to 6 months intervals. With a median follow up of 9.9 years from diagnosis (range, 0.4 - 30.9), 61% of patients maintained MRD negativity, while 39% experienced MRD conversion at a median of 6.3 years (range, 1.4 - 25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95%vs. 84%; P = 0.001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 year (range, 0 - 4.9). However, 27% of MRD conversion positive patients had not yet experienced a clinical relapse with a median follow-up of 9.3 years (range, 2.2 - 21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared to patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

scholarly journals The importance of serum immunoglobulin free light chain assessment for predicting outcome in patients with newly diagnosed multiple myeloma in real clinical practice

2020 ◽  
Vol 15 (3) ◽  
pp. 38-50
Author(s):  
N. V. Skvortsova ◽  
I. B. Kovynev ◽  
K. V. Halzov ◽  
T. I. Pospelova
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Practice ◽  
Blood Serum ◽  
Control Group ◽  
Newly Diagnosed ◽  
Lactate Dehydrogenase Activity ◽  
Immunochemical Study ◽  
Real Clinical Practice

Background. The prognosis of patients with multiple myeloma (MM) is significantly different depending on the biological characteristics of the tumor substrate, the microenvironment of the bone marrow, as well as factors associated with the patient’s body. Therefore, the search for new reliable and easily identifiable prognostic markers is relevant for the effective management of patients with this disease.The objective of the study was to assess the prognostic value of the study of serum free light chains (FLC) of immunoglobulins κ and λ and their ratio κ / λ FLC in the blood serum of patients with newly diagnosed MM in real clinical practice.Materials and methods. 369 patients with first diagnosed MM (134 men and 235 women) were examined who were hospitalized in the hematology department of the City Clinical Hospital No. 2 Novosibirsk in the period since January 2012 to December 2017. The median age of the patients was 67 (32–82) years. All patients received induction courses of chemotherapy based on bortezomib. The control group consisted of 56 conditionally healthy individuals: 34 women (60.7 %) and 22 (39.3 %) men with a median age of 62 (40–68) years. The concentration of FLC-κ and FLC-λ (mg / L) in blood serum was determined by immunoturbidimetric method on a Hitachi 911 automated biochemical analyzer using the Freelite Human Lambda and Freelite Human Kappa reagent kits (Binding Site, Great Britain).Results. It was found that in patients with MM, the concentration of serum FLC-κ or FLC-λ was statistically significantly higher compared to the control group and varied depending on the type of MM (p <0.001). The diagnostic sensitivity of the quantitative determination of FLC and their ratio for MM was 98.64 %, compared with 94.04 % in a standard immunochemical study. The values of the ratio κ / λ FLC <0.04 or> 65, as well as the concentration of FLC-κ and FLC-λ are higher than the median obtained in the whole group (FLC-κ ≥702 mg / L and FLC-λ ≥493.2 mg / L), correlate with known factors of poor prognosis for MM (with a high concentration of β2‑microglobulin (>3.5 mg / L) (r = 0.461; p <0.001), plasma cell bone marrow infiltration >60 % (r = 0.420; p <0.001), renal failure (creatinine >177 μmol / L) (r = 0.380; p = 0.002), and also with high lactate dehydrogenase activity (>450 U / L) (r = 0.520; p <0.001) and is associated with poor outcomes. The median overall survival in the group of patients with κ / λ FLC <0.04 or >65 was 49 months compared to 76 months in the group with κ / λ FLC 0.04–65 (log-rank p = 0.012).Conclusion. The determination of free FLC in the blood serum of patients with MM can be used to assess the prognosis of their survival. The value of the κ / λ FLC ratio <0.04 or >65 allows us to divide patients with MM into risk groups with significantly different outcomes and can be used to identify patients at high risk who need more aggressive therapy and more detailed monitoring of the response.

Anti-Angiogenic Effect of Bortezomib in Multiple Myeloma Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4912-4912
Author(s):  
Marianna Politou ◽  
Kikeri Naresh ◽  
Evangelos Terpos ◽  
Danielle Crowley ◽  
Irvin Lambert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Partial Response ◽  
Angiogenic Factors ◽  
Response To Treatment ◽  
Serum Samples ◽  
Bone Marrow Biopsies ◽  
Significant Difference ◽  
Before And After ◽  
Angiogenic Effect

Abstract Bortezomib is a proteasome inhibitor, which is an effective treatment for multiple myeloma (MM). Bortezomib inhibits NF-κB and thus enhances apoptosis and leads to reduced levels of growth factors, angiogenic factors and cell adhesion molecules, which are crucial for the growth and survival of myeloma. The aim of this study was to investigate whether bortezomib has an anti-angiogenic effect in MM patients and whether that effect correlates with response to treatment. We have studied the effect of bortezomib on angiogenesis in bone marrow biopsies and serum samples of nine patients with MM, who were treated with bortezomib. The patients studied (6M/3F median age 59 years, range 35–71 years) had received more than 4 lines of treatment before bortezomib administration. Six patients had IgG, one IgA, one non-secretory and one light-chain MM. Bortezomib was given at a dose of 1.3 mg/m2, iv, in 3-week cycles, on days 1, 4, 8, and 11 of each cycle. Microvessel density (MVD) was assessed in bone marrow trephine biopsies before and after 8 cycles of treatment by immunohistochemistry with monoclonal mouse antibodies to CD34 (QBEND-10, DAKO, Denmark). Serum samples were assessed for VEGF and angiogenin levels before and after every cycle of treatment with an ELISA (R&D systems). Five out of 9 patients achieved a partial response (PR), two patients had a minimal response (MR),one achieved a good partial response (GPR) and one a complete response (CR) to bortezomib administration, according to EBMT criteria. In six out of 9 patients there was a decrease of the MVD. More specifically in two of the patients with PR (P2,P4) and the two patients with MR (P5 and P7) there was a significant decrease in the MVD ( 1.7, 3.8, 4.2 and 1.4 fold decrease respectively). Patient 9, who achieved GPR had also a 2.3 fold decrease in MVD. In patients P2,P4,P5 and P6, who received 8 cycles of treatment, further reduction of MVD was noticed with further treatment. In patient 1, who achieved a PR, MVD did not show any significant change after 8 cycles of treatment. The patient relapsed soon after he has completed the treatment. In patient 5, the MVD increased over 2-fold and she relapsed very soon after the 4th cycle and died of disease progression. There was a significant reduction in mean angiogenin levels by cycle 4 (380 ng/ml) when compared with cycle 1 (537ng/ml) (p=0.028). On the contrary, there was no significant difference between the levels of VEGF at cycles 1 and 4 (122.5 pg/ml and 127.2 pg/ml respectively) (p=0.173).All data are shown in Table 1. We conclude that PS-341 may exert its anti-myeloma effect partly through anti- angiogenic mechanisms. Whether Bortezomib acts directly on endothelial cells or indirectly through modulation of the expression of angiogenic factors and angiopoetins which influence endothelial cell proliferartion and survival is unclear. Before treatment After 4th Cycle of treatment After 8th Cycle of treatment response to treatment VEGF(pg/ml)/Ang (ng/ml) MVD vessels/mm 2 VEGF(pg/ml)/Ang (ng/ml) MVD vessels/mm 2 VEGF(pg/ml)/Ang (ng/ml) MVD vessels/mm 2 patient 1 PR 213/642 74.1 813/432 428/361 83.99 Patient 2 PR 172/425 124.7 449/334 77.48 243/371 73.85 patient 3 PR 84/404 61/256 175/2 65 patient 4 PR 160/800 109.55 180/316 37.5 80/359 28.5 patient 5 MR 57/615 195.8 70/517 85.51 94/447 46.1 patient 6 PR 47/459 267 82/335 591.8 patient 7 MR 105.88 75.55 patient 8 GPR 48.89 2 patient 9 CR 135.78 57.14

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