Plasmocytosis and Immunoparesis but Not Neutrophil to Lymphocyte Ratio Can Predict Time to Treatment in Smoldering Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5358-5358
Author(s):  
Alessandra Romano ◽  
Marzia L Consoli ◽  
Marina Parisi ◽  
Maide Cavalli ◽  
Nunziatina L Parrinello ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Bone Lesion ◽  
Progression Free Survival ◽  
Absolute Lymphocyte Count ◽  
Bone Lesions ◽  
Time To Treatment ◽  
Smoldering Myeloma

Abstract Objectives: We recently identified the ratio between absolute neutrophils count and absolute lymphocyte count, NLR ≥2, as a predictor of progression free survival (PFS) and overall survival (OS) in patients younger than 65 years with symptomatic Multiple Myeloma (MM). We retrospectively examined the NLR in a cohort of 140 smoldering Myeloma (sMM) defined accordingly to the updated IMWG 2014 guidelines accessed our Center between June 2006 and June 2014. Methods: NLR was calculated using data obtained from the complete blood count (CBC) at diagnosis and subsequently correlated with time to treatment (TTT) for symptomatic MM. All patients underwent bone marrow evaluation to estimate plasma cells infiltration (BMPC), Magnetic Resonance Imaging (MRI) to detect bone lesions, serum free-lite chain evaluation (sFLC) starting from January 2012 when they became evaluable in our center. Results: The mean NLR was 2.0 ± 0.1, lower than the value previously found for MM (2.7 ± 0.2, p= 0.005). Higher NLR was independent of BMPC amount, cytogenetics and sFLC. Using NLR ≥2 as predictive biomarker we could not predict TTT. In univariate analysis only BMPC ≥ 30% (p<0.0001), immunoparesis (suppression of one or more uninvolved immunoglobulins, p=0.017) and presence of at least one bone lesion at MRI (p<0.0001) could predict TTT. In multivariate analysis, these three parameters were independent (p<0.0001). Since new guidelines consider BMPC≥ 60% and positive MRI as myeloma-defining events, we proposed a simplified score model based on BMPC ≥ 30% (1 point) and immunoparesis (1 point). We identified patients with score 0 (20%) as low-risk (TTT at 60 months 0%), with score 1 (61%) as intermediate risk (TTT at 60 months 61%) and with score 2 as high-risk (TTT at 60 months 22%, p<0.0001). Conclusion: We confirmed BMPC and immunoparesis as strong predictors of outcome in sMM. Disclosures No relevant conflicts of interest to declare.

Multiple Myeloma Associated GI Polyposis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5009-5009
Author(s):  
Nassim Nabbout ◽  
Mohamad El Hawari ◽  
Thomas K. Schulz
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Bone Marrow Failure ◽  
Bone Lesions ◽  
Rare Manifestation ◽  
History Of ◽  
Central Ulceration

Abstract Abstract 5009 Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells that can result in osteolytic bone lesions, hypercalcemia, renal impairment, bone marrow failure, and the production of monoclonal gammopathy. The gastrointestinal tract is rarely involved in myeloma. GI polyposis is a rare manifestation of extra-medullary disease in multiple myeloma. Such cases usually present as gastrointestinal hemorrhage or intestinal obstruction. A 53-year-old African American male recently diagnosed with multiple myeloma presented with three-day history of rectal bleed and fatigue. EGD showed multiple raised, polypoid, rounded lesions with a superficial central ulceration in the stomach. Colonoscopy showed similar lesions in the ascending and transverse areas of the colon that ranged in size from 5 to 16 mm in diameter. Biopsies showed that these polyps were made of plasma cells. A bone marrow biopsy showed diffuse involvement (greater than 90%) of bone marrow with multiple myeloma with anaplastic features. The patient was started on bortezomib at diagnosis, however, he passed away a few weeks later. This type of metastatic disease has been described in isolated case reports in the literature, while solitary GI plasmacytoma has been reported more frequently. In rare cases, multiple myeloma can involve the GI tract which may lead to bleed or obstruction. This involvement is likely a marker of aggressivity. This example of extra-medullary disease in myeloma is an uncommon variant with features of poor prognosis and dedifferentiation. Disclosures: No relevant conflicts of interest to declare.

Rituximab and High-Dose Dexamethasone (R-dex) Is Effective In The Treatment Of Relapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4184-4184
Author(s):  
Martin Simkovic ◽  
David Belada ◽  
Monika Motyckova ◽  
Lukas Smolej ◽  
Pavel Zak
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Antimicrobial Prophylaxis ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Published Data ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Tertiary Center

Abstract Introduction High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) but serious infections are frequent. Recently published data suggest that high-dose dexamethasone might be equally effective to HDMP despite lower cumulative dose. Aims To assess efficacy and safety of high-dose dexamethasone combined with rituximab (R-dex) in relapsed/refractory CLL. Patients and Methods A total of 60 pts (pts) with relapsed/refractory CLL treated at a single tertiary center between September 2008 and October 2012 were included in this retrospective analysis. Basic characteristics are summarized in Table 1. The schedule of R-dex consisted of rituximab 500 mg/m2 i.v. day 1 (375 mg/m2 in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13. Treatment was repeated every 3 weeks for a maximum of 8 cycles. All pts received antimicrobial prophylaxis with sulfamethoxazole/trimethoprim and aciclovir. Results Median number of administered R-dex cycles was 6 (range, 1-8). The overall response (ORR)/complete remissions (CR) were achieved in 75/3%. At the median follow-up of 9 months, median progression-free survival was 8 months and median overall survival 24 months. Significant predictors of short PFS in univariate analysis were bulky lymphadenopathy (p=0.023) and refractoriness to fludarabine (p=0.02). Interestingly, activity of R-dex in bulky fludarabine-refractory CLL was similar to ofatumumab (ORR 62 %, median PFS, 4 months, median OS, 12 months) (Wierda et al., 2010). R-dex was successfully used as a debulking regimen before allogeneic stem cell transplantation in 8 patients. Serious (CTCAE grade III/IV) infections occurred in 29% of patients; 19% pts developed steroid diabetes requiring temporary short-acting insulin. Conclusions Our data show that R-Dex is an active and feasible treatment for patients with relapsed/refractory CLL; however, major infections remain relatively frequent despite combined antimicrobial prophylaxis. In addition, durable responses are infrequent. Therefore, further optimization of this therapeutic approach is warranted. Updated results will be presented. Disclosures: No relevant conflicts of interest to declare.

CLINICOPATHOLOGICAL STUDY OF MULTIPLE MYELOMA WITH EXPRESSION OF CD56

2021 ◽  
pp. 2-3
Author(s):  
Jina Bhattacharyya ◽  
Gabyanjali Devi
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Bone Lesion ◽  
Immunoglobulin Superfamily ◽  
Bone Lesions ◽  
Plasma Cell Neoplasm ◽  
Disease Characteristics ◽  
Multisystem Involvement ◽  
Lytic Bone Lesion ◽  
Cd56 Expression

Background: Multiple myeloma (MM) is a plasma cell neoplasm with spectrum of clinical presentation and multisystem involvement. CD56 (a neural cell adhesion molecule, NCAM) is a membrane glycoprotein belonging to the immunoglobulin superfamily. Normal plasma cells do not express CD56, but it is frequently expressed by malignant plasma cells in patients with MM. The present study was conducted to evaluate the expression of CD56 in MM and its association with disease characteristics. Methods: We analysed CD56 expression in 34 newly diagnosed MM cases using immunohistochemistry in bone marrow core biopsies processed routinely. Results: CD56 expression was found in 70.97% cases. The clinicopathological disease characteristics such as age, serum creatinine level, serum β2-microglobulin level and plasmablastic morphology showed no statistically signicant difference between CD56 positive and negative groups. Bone lesions were signicantly higher in positive cases than in negative cases. Conclusion: CD56 expression dene a unique clinicopathological entity in MM. Expression of CD56 correlate well with lytic bone lesion and may correlate with its pathogenesis.

Outcome and treatment of 62 Patients Aged Over 75 Years with Low Grade Non Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4854-4854
Author(s):  
Anne Parcelier ◽  
Isabelle Leduc ◽  
Lavinia Merlusca ◽  
Gandhi Damaj ◽  
Amandine Charbonnier ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Low Grade ◽  
Albumin Concentration ◽  
Charlson Score ◽  
Non Hodgkin Lymphoma ◽  
Number Of Patients

Abstract Abstract 4854 The incidence of B cell Non Hodgkin Lymphoma (NHL) is steadily increasing with age and about 40% of cases occur in patients aged over 70 years. Some series have reported that low grade NHL lymphomas represent about 35% of all B NHL in elderly patients. However few data are available on the outcome of patients aged over 75 years. Methods We report in a retrospective study the outcome and management of 62 patients aged over 75 years and followed between Jan, 2006, and Jan, 2012 from 2 french centers (Amiens, Abbeville). The primary endpoint was overall survival (OS); secondary endpoints were response rates, progression free survival (PFS), and toxicity. Results 62 patients were registered with median age of 80,4 years (75–92): 31 patients with follicular lymphomas (FL) and 31 other low grade LNH: 15 Marginal Zone Lymphomas (MZL) of witch 11/31 splenic MZL, 1 gastric MALT, 5 lymphoplasmocytic and 10 lymphocytic lymphomas. At diagnostic, evaluation included: computed tomography scan for 46/62 patients (76%), bone marrow biopsy: 17/62 (27%), abdominal echography for 13/62 (24%) patients, echocardiography 24/62 (39%) and positron emission tomography for 11/62 (17%) patients. Charlson score (0–27) was evaluable for all of them with a median score of 2(0–4). At analysis, the median follow up was 23 months (range 0–79). Median FLIPI was 3 (0–5) for FL and median IPI 3(0–5) for other NHL. 21/31 (68%) FL patients and 27/31 (87%) other NHL had stage III or IV in the Ann Arbor classification. 47/62 (76%) patients received chemotherapy: 27/31 (89%) FL patients and 20/31 (65%) with other NHL. 12/62 (19%) patients were undergoing watchfull waiting (11 patients with other NHL, 1 FL); 1 patient refused chemotherapy; 1 FL patient died before any treatment. 29/47 (61%) treated patients received Rituximab (R). In the FL group, 12/31 (39%) received RCVP (C=Cyclophosphamide, V=Etoposide, P=Prednisone), 12/31 (39%) RCHOP-like regimen, 2/31 (6%) chlorambucil, 1/31 (3%) corticotherapy alone, 1/31 (3%) radiotherapy alone and 2/31 (6%) chemotherapy plus radiotherapy. For other low grade NHL, 2/31 (6%) received RCVP, 3/31 (9%) RCHOP-like regimen, 10/31 (32%) Chlorambucil, 1/31(1%) Fludarabine, 4/31(13%) orally cyclophosphamide and corticosteroid. 17 on 47 treated patients (36%) were in complete remission: 10/27 (37%) FL and 7/20 (35%) other NHL. The 2-years OS was 67%: 61% in the FL group and 74% other NHL (difference not significative); the 2-years PFS was 68%: 60% for FL and 77% for other low grade NHL. In univariate analysis, OS was affected by IPI (p=0,02) and FLIPI (p=0,008) (figure), but not by serum albumin concentration ≤ 35g/L, lymphopenia ≤1G/L, or Charlson score. 25 deaths were reported (14 FL and 11 other NHL): 9 lymphoma progressions, 6 sepsis, 3 attributed to cardiac failure and 1 to pulmonary embolism. The most frequent side-effects were hematological: febrile neutropenia (15 patients) and cardiac: acute failure (4 patients). Conclusion Our results in older patients with low grade lymphoma compare favorably with results in younger population. IPI and FLIPI only affect OS whereas geriatric evaluation with Charlson score is not relevant, possibly due to the small number of patients and short follow-up. These results prompt us to realize prospective studies in this population, reducing toxicity and improving efficacy with novel approach. Disclosures: No relevant conflicts of interest to declare.

Abnormalities Of FAM46C, AHCYL1, CDC14A and CDKN2C Genes Located At Chromosome 1p Detected By QM-FISH Identifies Deletion Of 1p32.3 Covered CDKN2C Is An Independent Adverse Prognostic Marker In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3145-3145
Author(s):  
Fei Li ◽  
Li-ping Hu ◽  
FengYan Jin ◽  
Yan Xu ◽  
Gang An ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Artificial Chromosome ◽  
Chromosome 1 ◽  
Chromosome 1P ◽  
Large Size ◽  
1P Deletion ◽  
The Impact

Abstract SNP arrays and FISH showed Chromosome 1 appeared as a critical region in MM pathogenesis and was associated with adverse survival, such as: 1q gain and 1p deletion. Recent years, some studies found deletions of some genes in the common minimum deletion regions on 1p were related to adverse prognosis, such as FAM46C at 1p12, CDC14A at 1p21.2, CDKN2C at 1p32.3. However, these studies were limited to one or two regions and lacked the comparison among the effects of different sites on prognosis. The characteristics of chromosome 1p abnormalities are not clear and no uniform consensus has been obtained that which locus is the best prognostic factor suitable for clinical routine detection. In addition, there's lack of data on the impact of 1p abnormalities on homogeneous group of patients. We investigated the abnormalities of FAM46C, AHCYL1, CDC14A, CDKN2C genes located at chromosome 1p12, 1p13.3, 1p21.2 and 1p32.3 by quantitative multicolor-fluorescence in situ hybridization (QM-FISH) using bacterial artificial chromosome (BAC) clones in 230 previously untreated myeloma patients. FAM46C, AHCYL1, CDC14A, CDKN2C genes were labeled with Green-dUTP (green), promoFluor-555-aadUTP (orange), PF590-dUTP (Red) and PF415-dUTP (Blue) and used as a FISH probe. The results demonstrated the deletion rates of 1p12, 1p13.3, 1p21.2 and 1p32.3 were 13.0%, 18.7%, 20.8% and 9.06% respectively. The deletion rate of 1p was 24.2%. Amplifications of 1p with 3.04%, 2.60%, 3.77% and 4.15% respectively in 1p12, 1p13.3, 1p21.2 and 1p32.3 were detected in some patients. These amplifications were significant lower than those of deletions (P=0.000, 0.000, 0.000, 0.021). Interestingly, we found chromosome 1p abnormalities were complex, various in forms. Among 57 patients with del(1p), 26.3% of patients presented with one locus deletion, 22.8% with two loci loss, 35.1% with three loci loss, 15.8% with four loci loss. Most (73.7%) of del (1p) were large size of deletion (≥ two regions). Del (1p) was positively correlated with high LDH (≥220U/L) (P=0.026), del (13q14) (P=0.023), and high percentage of plasma cells in bone Marrow (≥ 50%) (P=0.001). 108 patients were homogeneously treated with thalidomide-based chemotherapy (TAD/MPT). Survival analysis showed the median progression-free survival (PFS) of patients with and without del (1p) were 13.0 vs.26 months (P=0.002), median overall survival (OS) were 15.5 vs. 39.5 months (P=0.000). In addition, we found patients with sole del (1p) involving 1p12 or/and 1p13 had no worse prognosis. Patients with del (1p32.3) had shorter PFS (9.0 vs. 23.0, P=0.001) and OS (9.0 vs. 39.0, P=0.000). In multivariate analyses, 1p32.3 deletion appeared as an independent negative prognostic factor regarding to complex karyotype, LDH≥220U/L and del (17p13) in thalidomide-based chemotherapy group. Hazard ratio showed that the progression risk and death risk in patients with 1p32.3 were increased 5.64 (P=0.031) and 8.314 times respectively (P=0.011). Conclusion our datas show that chromosome 1p abnormalities are complex, various in forms, mainly with large size of deletion, rarely amplification. 1p deletions are negative prognostic factors for PFS and OS in MM patients receiving thalidomide-based chemotherapy. 1p32.3 deletion is the most important 1p deletion and is an independent poor factor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of CRBN Signaling Pathway Proteins Assessed By Immunohistochemical Staining As Candidate Biomarkers for Outcome in Myeloma Patients Treated with IMiDs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1909-1909
Author(s):  
Lijuan Chen ◽  
Qinglin Shi ◽  
Rong Wang ◽  
Xiupan Lu ◽  
Yan Gu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Signaling Pathway ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Expression Level ◽  
Positive Staining ◽  
Myeloma Cells ◽  
Low Level ◽  
First Line Therapy

Abstract Cereblon (CRBN), Ikaros (IKZF1), Aialos (IKZF3) and multiple myeloma oncogene 1 (MUM1) are important component of CRBN signaling pathway when treat MM cells with IMiDs. CRBN interacts with the DNA damage-binding protein-1 (DDB1), Cullin 4 (Cul4A or Cul4B) and regulator of Cullins 1 (ROC1) to form the functional E3 ubiquitin ligase complex (E3ULC). CRBN increases the interaction between E3ULC and IKZF1/3, leading to increased ubiquitination degradation of IKZF1/3, and then induce cytotoxicity in myeloma cells. Subsequently, degradation of IKZF1/3 induce depression of multiple myeloma oncogene 1 (MUM1), which is also called interferon regulatory factors (IRF4) and proved to be involved in the anti-MM activity of IMIDs in previous studies. Immunohistochemical (IHC) staining may be a convenient approach for researchers to differentiate the myeloma cells and non-myeloma cells in BM samples. In this study, we evaluated CRBN, IKZF1/3 and MUM1 expression level in bone marrow (BM) by immunohistochemical (IHC) staining and investigated the relationship between expression level and treatment outcome after IMiDs-based or bortezomib-based therapy in 123 newly diagnosed multiple myeloma (NDMM) patients. H-score method was applied according to both intensity and extent of staining. The intensity was graded from 0 to 3("0"for absent staining, "1" for weak expression, "2" for intermediate expression, and "3" for strong expression of the protein). The extent was graded from "0" to "100" to represent the percentage of MM cells with positive staining of any intensity. H-score was obtained by multiplying the intensity and extent score, ranging from 0 to 300, which reflected protein expression level in MM cells. The median H-score of CRBN, IKZF1, IKZF3 and MUM1 were 200, 0, 180 and 180, respectively. According to the median H-score, we classified the patients into high or low expression group. One hundred and twenty-three NDMM patients were enrolled in this study, including 64 males (52.0%) and 59 females (48.0%). The median age was 60 years (range 34-84). Fifty-one patients (41.5%) received IMiDs-containing regimen as the first-line therapy. The median follow-up time was 24.0 months (range, 10-76 months). After treated with IMiDs, patients with high level of CRBN and MUM1 achieved better overall response rate (ORR) than those expressed low level (CRBN, 88.0% vs. 42.3%, P=0.001; MUM1, 83.3% vs. 48.1%, P=0.009). Besides, patients with CRBN and MUM1 overexpression also had better overall survival (median OS, CRBN, not reached vs. 21.0 months, P=0.004; MUM1, not reached vs. not reached, P=0.021) and progression free survival (median PFS, CRBN, 28.0 vs. 12.0 months, P=0.002; MUM1, 32.0 vs. 12.0 months, P<0.001) than patients with low level, as well as 2-year OS rate (CRBN, 86% vs. 44%, P=0.005; MUM1, 81% vs. 51%, P=0.003) and PFS rate (CRBN, 66% vs. 17%, P=0.001; MUM1, 63% vs. 20%, P<0.001). In addition, in high CRBN and MUM1 expression group, patients treated with IMiDs had a higher 2-year PFS rate than Bortezomib presentation (CRBN, 66% vs. 45%, P=0.004; MUM1, 63% vs. 36%, P=0.003). In low CRBN and MUM1 expression group, patients treated with IMiDs had an inferior OS (median OS, CRBN, 21.0 vs. 57.0 months, P=0.001; MUM1, not reached vs. 57.0 months, P<0.001) and PFS (median PFS, CRBN, 12.0 vs. 31.0 months, P=0.003; MUM1, 12.0 vs. 32.0 months, P<0.001) than patients with Bortezomib, as well as 2-year OS rate (CRBN, 44% vs. 91%, P=0.002; MUM1, 51% vs. 100%, P<0.001) and PFS rate (CRBN, 17% vs. 59%, P=0.010; MUM1, 20% vs. 68%, P<0.001). This study identified high levels of CRBN pathway proteins CRBN and MUM1 were correlated with favorable ORR and survival in NDMM patients with IMiDs therapy, also suggested that expression levels of CRBN signaling pathway proteins in plasma cells assessed by IHC staining could better direct clinic individualized therapy. Disclosures No relevant conflicts of interest to declare.

A Phase II Trial of TBL 12 Sea Cucumber Extract in Patients with Untreated Asymptomatic Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3992-3992
Author(s):  
Ajai Chari ◽  
Amitabha Mazumder ◽  
Lauren Ditrio ◽  
Zachary Galitzeck ◽  
Sundar Jagannath
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Pneumococcal Pneumonia ◽  
Sea Cucumber ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Bone Lesions ◽  
Open Label ◽  
M Spike

Abstract Abstract 3992 Background: Patients with smoldering multiple myeloma (MM) may remain asymptomatic (ASx) for variable amounts of time and are therefore typically monitored without treatment. Chemoprevention trials using thalidomide have found the toxicity to be prohibitive and longer follow up is needed for the early systemic treatment with lenalidomide and dexamethasone of high risk ASxMM. Based on encouraging preclinical data with bioactive food supplements in MM curcumin (Bharti et al., Blood 2003), resveratrol (Bhardwaj et al, Blood 2006), and a component of green tea extract (Shammas et al, Blood 2006) many patients are already using these agents without definitive proof of efficacy or safety. The sphingolipids/glycosides contained in sea cucumbers have also been shown preclinically to have a number of antitumor properties including antiangiogenesis direct tumor cytotoxicity, and also of particular relevance to MM, the inhibition of osteoclastogenesis (Kariya et al, Carb Res 2004). TBL12, an extract of sea cucumber, has been commercially available since 1981 and used by human subjects as a food supplement without any reported toxicities. We therefore designed a pilot phase II study to determine the safety and efficacy of TBL12 in patients with ASxMM and here we present updated data. Methods: Patients were required to have ASxMM with measurable disease, defined as monoclonal immunoglobulin spike (m-spike) on serum electrophoresis of ≥ 1 g/dL and/or urine m spike of ≥ 200 mg/24 hours. If non-secretory, then abnormal free light chains (FLC) were required. A total of 20 patients with ASxMM were given open label TBL12, formulated as a liquid gel (manufactured by Unicorn Pacific Corporation, IND 103,543) to be kept frozen until the time of consumption. Patients ingested 2 units of 20 ml twice per day, for a total of 80 units per day. Disease parameters were monitored monthly and treatment was continued until disease progression. Results: 23 patients were screened, with 3 failures, and the remaining 20 patients proceeded with study treatment. The median age of the patient was 58 years (range 22–75), with 11 males and 9 females. The phenotypes were 14 IgG, 5 Ig A, and one kappa light chain. Generally, this was a population at high risk for progression of disease (PD), with 14 patients having a serum m spike > 3 g/dl and bone marrow plasma cells (BM PC) > 10%. The median BM PC for all patients was 38% (range 10 to 90). (With the additional high risk criteria of a FLC ratio <0.125 or >8, 13 patients were high risk.) Of the remaining 6 patients, all had immunoparesis and 4 had markedly elevated FLC ratios (range 307-incalculable) and the remaining 2 patients had 9.2 g urine m spike and an IgA phenotype. Compliance was excellent and the treatment was well tolerated with only grade 1 nausea. There was one SAE, a pneumococcal pneumonia requiring admission, which was felt to be unrelated to study treatment. A total of 9 patients remain on treatment, having completed a median of 24 monthly cycles of TBL12 (range 20–30 cycles). The median progression free survival (PFS) has not been reached by Kaplan-Meyer survival analysis, including for high risk patients. The best response to date has been a minimal response (MR) for 5 cycles. 3 patients are on intermittent bisphosphonates therapy q 3–12 months for osteoporosis or equivocal bone lesions unchanged since screening. 8 patients came off study for PD after a median of 7.5 cycles (range 2–18). The reasons for PD include: 1 hypercalcemia, 1 acute renal insufficiency (after 2 cycles with 9.2g urine m spike at screening), 2 for anemia (one after 3 cycles with 90% BM PC at screening), and 1 for a new bony lesion on MRI. 2 patients withdrew consent after cycle 6 and 8, and 1 was removed after cycle 13 due to investigator discretion after the pneumococcal pneumonia SAE. Conclusions: In this pilot study of high risk ASxMM patients, TBL12 is well tolerated and 9 (45%) patients remain on treatment with one MR noted. The expected rate of PD for high risk ASxMM is 52% at 2 years (Dispenzieri et al, Blood 2008) and to date, median PFS has not been reached in this study. Also, of note, in contrast to 10 of 16 pts in the placebo arm of lenalidomide in ASxMM study developing bone PD (Mateos et al, ASH 2009), only 1 patient in this study has bone PD. This may reflect anti-osteoclastogenesis effects of TBL12 observed in vitro. Further studies are required. Disclosures: No relevant conflicts of interest to declare.

Effect Of Low Dose Bortezomib On Bone Formation In Smoldering Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3204-3204 ◽  
Author(s):  
Maurizio Zangari ◽  
Tamara Berno ◽  
Mohamed E Salama ◽  
Sherjeel Sana ◽  
Giampaolo Talamo ◽  
...  
Keyword(s):  
Bone Density ◽  
Research Funding ◽  
Low Dose ◽  
Plasma Cells ◽  
Bone Lesions ◽  
T Score ◽  
Score Improvement ◽  
Grade 3 ◽  
Smoldering Myeloma

Abstract Background Bortezomib has been shown to produce an anabolic bone effect (increase bone ALP and osteocalcin) in relapsed/refractory patients. This study examined the bone anabolic effect in patients with smoldering multiple myeloma (SMM) who, with a historical median age of 67 years, have frequent evidence of osteopenia not associated with lytic bone disease. SMM is usually followed expectantly without therapy. The overall risk of progression to active MM has been estimated up to 20% in the first year from diagnosis (Kyle et al, 2007). The primary aim of this trial is to determine the effect of a course of low-dose Bortezomib on bone remodeling and on disease progression. Methods The dose of bortezomib used in this trial of 0.7mg/m² is the lowest dose which has shown efficacy in the 3 largest monotherapy trials with bortezomib. Patients enrolled in this study had serum M protein ≥ 3 g/dL and/or bone marrow plasma cells ≥ 10% with absence of anemia, renal failure, hypercalcemia, and lytic bone lesions. Patients received 9 cycles of bortezomib given on days 1, 8, 15, 22 every 42 days. No bisphosphonates were allowed during the trial, Vitamin D supplements were allowed. Results Seventeen patients (9 males) with a median age of 61 years were enrolled in the study. Fourteen had IgG paraprotein and 3 had an IgA. Two participants did not complete the treatment; the first because of development of a skin rash and the second for personal reasons. A total of 11 patients completed the protocol. Four are still receiving treatment. At the time of this analysis with a median follow-up of 20 months, all patients are alive and none has progressed (Figure 1). The mean M component at baseline, end-of-study, and at most recent follow-up are shown in Figure 2. The treatment was well tolerated by the patients. One patient developed reversible grade 3 neuropathy and a drug related rash and only 3 grade 3 hematological adverse events were recorded (15%). Bone densities by DEXA scan were obtained at baseline, end of study, and yearly thereafter. Out of 17 patients, 13 had bone density T-scores before and after treatment. Six patients (46%) showed an improvement in hip T-score (mean T-score improvement 0.41, range 0.1-1.35). In the overall group, mean T scores improved by 38% (range, 3-200%). T score in lumbar spine improved in 3 patients (23%), who had a mean T-score improvement of 0.2 (range, 0.05-0.43). Conclusions The use of low dose Velcade in smoldering myeloma patients was well tolerated and produces significant increases in bone density in 46% of participants. Disclosures: Zangari: Millenium Pharm.: Research Funding. Off Label Use: Use of Bortezomib in smoldering myeloma. Salama:Eli Lilly and Co: Research Funding.

[18F]NaF PET/CT imaging biomarkers of progression-free survival in metastatic prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 277-277
Author(s):  
Stephanie Harmon ◽  
Tim Perk ◽  
Jens C. Eickhoff ◽  
Mary Jane Staab ◽  
Peter L. Choyke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Imaging Biomarkers ◽  
Great Promise ◽  
Bone Lesions ◽  
Free Survival ◽  
Functional Changes ◽  
Skeletal Involvement ◽  
Pet Ct

277 Background: 18F-Sodium Fluoride (NaF) PET/CT has been shown to be superior to 99mTc-MDP SPECT in detection of bone metastases and shows great promise to reliably measure functional changes in bone. This study assesses the relationship of Progression Free Survival (PFS) with NaF PET/CT measures in patients with metastatic Castration-Resistant Prostate Cancer (CRPC). Methods: 55 CRPC patients had NaF PET/CT scans performed at baseline, which was repeated at week 9 if receiving taxane-based therapy (N = 16) or week 12 if receiving androgen-signaling pathway (AR) inhibitors (N = 39). Bone lesions were identified using a novel technique allowing for extraction and tracking of PET metrics from individual lesions at every timepoint. Cox proportional hazard regression analyses were conducted to evaluate associations between imaging metrics and PFS. Results: Median PFS was 8.3 months (range 1.0-30.3+). The strongest predictor of PFS in univariate analysis was total functional burden (SUVtotal) (P < 0.0001) during treatment for all patients. Predictors of PFS differed between both treatment cohorts of patients (Table 1), including number of lesions, fraction of skeletal involvement, and average lesion activity (SUVmean). Maximum PSA benefit (percent decrease) during the first 12 weeks of therapy was highly predictive of PFS in the AR-directed cohort of patients (HR = 1.012 , P = 0.0005), as was change in the number of lesions (HR = 1.01, P = 0.03). Conclusions: There is indication thattotal functional burden of disease during treatment with taxane or AR-directed therapy is a strong predictor of PFS. In addition, change in number of lesions was predictive of treatment efficacy. This supports ongoing development of NaF PET/CT based imaging biomarkers in mCRPC. Clinical trial information: NCT01516866. [Table: see text]

Absolute lymphocyte count in patients with glioblastoma treated with temozolomide chemoradiation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13564-e13564
Author(s):  
Anas Saeed Bamashmos ◽  
Assad Ali ◽  
Addison Barnett ◽  
Soumya Sagar ◽  
Lisa A. Rybicki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lymphocyte Count ◽  
Univariate Analysis ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Absolute Lymphocyte Count ◽  
Primary Objective ◽  
Start Date ◽  
Grade 3

e13564 Background: Standard glioblastoma (GBM) management includes radiotherapy, chemotherapy, and steroids; all of which can result in immunosuppression and a low absolute lymphocyte count (ALC). Previous literature identified an association between low CD4 and worse progression free survival (PFS) and overall survival (OS). There remains a lack of research addressing predictors of immunosuppression in patients with GBM. The primary objective of this study is to identify the degree of immunosuppression, measured by ALC, in GBM patients receiving concurrent temozolomide chemoradiation (CRT). Secondary objectives include associations between ALC, PFS, and OS, and whether there are any predictors of immunosuppression in patients with GBM. Methods: We retrospectively reviewed 231 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between ALC and age, sex, MGMT methylation status, and extent of surgical resection. ALC was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Common Terminology Criteria for Adverse Events (CTCAE) protocol version 5.0 was then used to grade low ALC as grade 0, 1, 2, 3, or 4. Results: Of the 231 patients analyzed, 139 were males, 74 underwent gross total resection of the tumor, 129 patients were less than 65 years, and 79 (42.5%) were MGMT methylated. 37 patients had grade 3-4 low ALC. In a univariate analysis, grade 3-4 low ALC at 4 weeks (±14 days) post-CRT start was associated with higher mortality (HR 1.54, P = 0.028) but had no significant association with PFS (HR 1.22, P = 0.29). Logistic regression analysis was used to identify risk factors for grade 3-4 low ALC and its association with survival. None of the risk factors that we tested such as age, gender, type of surgery, or molecular markers including MGMT, IDH, or EGFR were associated with low ALC. Conclusions: Our study demonstrated that patients with ALC grade 3 or 4 at 4 weeks (±14 days) of CRT had a significantly higher mortality (HR 1.54, P = 0.028) but had no significant association with PFS (HR 1.22, P = 0.29).

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