Distress Screening Scores of Malignant and Benign Hematology Patients: Results of a Pilot Project.

Abstract Abstract 3173 The Cleveland Clinic Taussig Cancer Institute completed a pilot project on distress screening as part of the plan to address the American College of Surgeons Commission on Cancer requirement (Standard 3.2: Psychosocial Distress Screening) to screen malignant and benign hematology patients for distress and psychosocial health needs. Over a two week period every hematology patient seeing a physician or mid-level provider completed the distress screening instrument Emotions Thermometer (ET), a five dimensional tool that includes four predictor domains: distress, anxiety, depression, anger and one outcome domain of need for help. Each domain is rated on a 0 to 10 Likert type scale, in a thermometer format. With respect to validity and reliability, the sensitivity and specificity of the ET tool has been found comparable to known validity and reliability of other accepted measures of distress, depression, and anxiety (Mitchell, et al, 2009). Per National Comprehensive Cancer Network (NCCN) guidelines, a score of 4 or higher on distress screening warrants a referral to a psychosocial professional. Distress scores 4 and over were compared among the diagnoses using the Chi-Square test. When the overall P-value was significant (P <0.05), at least two groups differed, and pairwise comparisons were conducted to determine which diagnostic groups differed. Of the five thermometer domains, patients scored highest on anxiety. There were no differences among diagnoses on anger (P=0.51), but there were differences in the other four domains (P<0.001 distress, depression, and need for help; P=0.026 anxiety). For all four, pairwise comparisons indicated that multiple myeloma patients had higher (worse) scores on anxiety, distress, depression, and need for help than all other diagnoses; there were no differences among benign hematology, leukemia/MDS/CML, or lymphoma/CLL. While this pilot project does not answer why multiple myeloma patients report levels of psychosocial distress significantly higher than other hematology patients, increased attention needs to be given to address these patients' experience of anxiety, depression, and distress. This project provides valuable information about the levels of distress experienced among all hematology patients and is useful for determining staffing levels of psychosocial professionals needed to address distress. Percentage of Emotion Thermometer Scores Over 4 Diagnosis Distress Anxiety Depression Anger Help Benign Hem 18% 27% 18% 12% 7% Leuk/MDS/CML 19% 28% 17% 9% 14% Lymph/CLL 18% 31% 16% 14% 13% Myeloma 38% 44% 35% 15% 27% P-value <0.001 0.026 <0.001 0.51 <0.001 Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A Better Mobilization Regimen for Newly Diagnosed Multiple Myeloma Patients,

Blood ◽

10.1182/blood.v118.21.4051.4051 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4051-4051

Author(s):

Ahmed Y Abuabdou ◽

Eric R Rosenbaum ◽

Saad Usmani ◽

Bart Barlogie ◽

Michele Cottler-Fox

Keyword(s):

Multiple Myeloma ◽

Conflicts Of Interest ◽

Optimal Number ◽

P Value ◽

Newly Diagnosed ◽

The Poor ◽

Cd34 Cells ◽

Significant Difference ◽

Minimum Number ◽

Poor Mobilizer

Abstract Abstract 4051 Introduction: What constitutes an acceptable mobilization regimen for collecting CD34+ cells depends on whether the goal of collection is to obtain a minimum number versus optimal number of cells. When treating patients with high-risk myeloma it may be important to obtain an optimal number. Here we compare retrospectively our earlier mobilization regimen, VTD-PACE, with MVTD-PACE in newly diagnosed, previously untreated multiple myeloma patients. Materials and Methods : We reviewed data for all patients who collected hematopoietic progenitor cells on Total Therapy protocols TT3a/TT3b with VTD-PACE (n=394) from February 2004 to September 2008 (138 females and 256 males, median age 59y; range 31–75), and on TT4/TT5 with MVTD-PACE (n=188) from August 2008 to May 2011 (78 females and 110 males, median age 61y, range 30–76). Based on their predicted first day collection with a large volume leukapheresis (30L processed), using our center's predictive formula (Blood 2010; 116(21):1182a), patients were stratified into 4 mobilizer types: poor (<2×106 CD34+ cells/kg), intermediate (≥2 to 10×106), good (>10 to 20×106) and excellent (>20×106). Variables examined included number of CD34+ cells/μl blood on day 1 and day 2 of collection (we have a minimum 2 day collection requirement), number of collection days to reach our minimum goal of 20×106 CD34+ cells/kg, and total CD34+ cells/kg collected for both chemotherapy groups. Variables for both groups stratified by mobilizer type were compared using two-tailed student's t-tests, except for the poor mobilizer group, where population size was too small for formal statistical analyses (VTD-PACE n=7, MVTD-PACE n=4), although averages were calculated. Results : There was no significant difference between VTD-PACE and MVTD-PACE for CD34+ cells/μl blood on day 1 of collection among the excellent [mean 368.9 (n=184) vs. 434.6 x106 (n=92); p-value 0.07], good [mean 138.6 (n=102) vs. 128.6 x106 (n=40); p-value 0.19], and intermediate [mean 60.1 (n=100) vs. 55.9 x106 (n=52); p-value 0.39] groups. A statistically significant difference between VTD-PACE and MVTD-PACE was found for CD34+ cells/μl blood on day 2 of collection for excellent mobilizers [mean 333.8 (n=184) vs. 460 ×106 (n=92); p-value <0.001], but not for the good [mean 165.7 (n=102) vs. 189.5×106 (n=40); p-value 0.21] and intermediate [mean 80.1 (n=101) vs. 102.3 ×106 (n=52); p-value 0.07] groups. When CD34+ cell/kg collection totals with VTD-PACE and MVTD-PACE were compared, a significant difference was seen for the intermediate mobilizer group only [mean 23.6 (n=101) vs. 26.3 ×106 (n=52); p-value 0.03]. For the poor mobilizer group, VTD-PACE had an average CD34+ cells/μl blood of 13.5×106 for day 1 of collection and 17.0 ×106 for day 2, with a total of 14.5×106 CD34+cells/kg collected; while MVTD-PACE had an average of 13.2×106 CD34+ cells/μl blood for day 1 of collection, 24.9×106 for day 2, with a total of 24.2×106CD34+ cells/kg collected. The number of collection days was similar between VTD-PACE and MVTD-PACE in the excellent mobilization group (2 days), but was slightly more for VTD-PACE compared to MVTD-PACE for the good (2.1 vs. 2 days), intermediate (3.2 vs. 2.9 days), and poor (6.1 vs. 5.8 days) groups. Conclusion : Both regimens allow more than minimum collections, but MVTD-PACE provides a higher peak number of CD34+ cells/μl blood, resulting in a slightly lower mean number of days of collection than VTD-PACE to reach an optimal collection. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Original Versus Generic Lenalidomide in Patients with Relapsed Multipl Myeloma: Comprasion of Effectivity and Adverse Events

Blood ◽

10.1182/blood-2019-131093 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5594-5594

Author(s):

Zahit Bolaman ◽

Sehmus Ertop ◽

Atakan Turgutkaya ◽

Selim Cem ◽

Ayse Hilal Eroglu Kucukerdiler ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Adverse Events ◽

Conflicts Of Interest ◽

Complete Response ◽

Muscle Cramp ◽

P Value ◽

Medicine Department ◽

School Of Medicine ◽

Number Of Patients

Original versus generic lenalidomide in patients with relapsed multipl myeloma: Comprasion of effectivity and adverse events Ali Zahit Bolaman1, Sehmus Ertop2 Atakan Turgutkaya1, Cem Selim, 1 Ayse Hilal Eroglu Kucukerdiler1, Birsen Sahip2, Irfan Yavasoglu1. 1 Adnan Menderes University, School of Medicine, Department of Hematology AYDIN/TURKEY 2 Bulent Ecevit University School of Medicine, Department of Hematology ZONGULDAK/TURKEY Backround: Lenalidomide is an effective IMID derivative drug in the treatment of patients with multiple myeloma. Lenalidomide is available as original and generic forms in our country. So far, there is no any clinical study comparing generic and original lenalidomine for effectivity and adverse events. We compared generic and original lenalidomide effects and adverse events (AEs) in patients with relapsed multiple myeloma (RMM). Methods: The patients with RMM using original or generic lenalidomide were evaluated as retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease and progressive disease rates and also for adverse events, development rates of neutropenia, anemia, thrombocytopenia, febrile neutropenia, anorexia, constipation diarrhea, nausea, vomiting, creatinine increase, transaminase increase, asthenia, fatigue, pyrexia, peripheral edema, upper respiratory system infection, pneumonia, another infection, muscle cramp, back pain, bone pain, muscle weakness, arthralgia, headache, tremor, paresthesia, deep vein thrombosis, pulmonary embolism, hyperglycemia, hypokalemia, hypocalcemia, hypomagnesaemia, skin dry and skin erythema were investigated in myeloma patients. All data were analyzed using the PASW for Windows version 19.0 (SPSS Inc., Chicago, IL, USA). The results were described as a number, frequency, and percentage. The chi-squared test and Fisher's exact test were used for the analysis of categorical data and independence between variables. The results were assessed at 95% confidence interval and p-value of less than 0.05 was accepted as significant. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. OR rate was 60 % versus 39.5% in patients using original and generic lenalidomide, respectively. CR rate was 14.5%, VGPR was rate 45.4% in original group while CR rate was 20.9 and VGPR 18.6 in patients using generic lenalidomide. AEs were low in original lenalidomide group than generic group. AEs were usually grade 1 or 2. Response and AEs rates are shown in Table 1. Conclusion: Our study showed original and generic forms of lenalidomide are effective for the treatment of RMM. OR rate was higher in original lenalidomide than generic lenalidomide. The AEs of original lenalidomide were lower than generic lenalidomide without statistically significance. Further studies involving a larger number of patients with RMM would be useful for comparing the efficacy and AEs of original or generic lenalidomide. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Polymorphisms in Regulators of Xenobiotic Transport and Metabolism Genes NR1I2 and NR1I3 and Multiple Myeloma Risk: A Case-Control Study in the Context of IMMEnSE Consortium

Blood ◽

10.1182/blood.v118.21.5014.5014 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5014-5014

Author(s):

Gabriele Buda ◽

Alessandro Martino ◽

Daniele Campa ◽

Juan Sainz ◽

Rui Manuel Vieira Reis ◽

...

Keyword(s):

Multiple Myeloma ◽

Genetic Variation ◽

Conflicts Of Interest ◽

Individual Variability ◽

P Value ◽

Genotype Distribution ◽

Nucleotide Polymorphisms ◽

Elimination Process ◽

Increased Risk ◽

The Impact

Abstract Abstract 5014 Exposure to toxic compounds and pesticides leads to an increased risk to develop Multiple Myeloma (MM). The metabolism and the excretion of xenobiotics are mediated by the enzymes and transporters acting in the detoxifying/elimination process. The nuclear receptors NR1I2 (or PXR) and NR1I3 (or CAR) act as xenosensor activating the detoxifying/elimination process in response to the intracellular levels of xenobiotics. It has been hypothesized that part of the individual variability in drug metabolism efficiency could be due to the genetic variations within these regulator genes affecting their expression and/or function. To investigate the impact of genetic variation within these genes on MM susceptibility, we selected and genotyped 10 tag Single Nucleotide Polymorphisms (SNPs) in the PXR gene and 7 tag SNPs in the CAR gene in 627 MM cases (320 males and 307 females) and 883 (459 males and 424 females) controls from different European populations. All the SNPs were in Hardy-Weinberg equilibrium (p>0.001), with the exception of the PXR SNP rs2461818 that was therefore excluded from the analysis. We found no association of any of the genotyped SNPs with MM risk. In the same way, haplotype distribution showed no differences between cases and controls. This was the first comprehensive investigation of genetic variation in xenobiotic regulators genes PXR and CAR in relation to MM risk and our data suggest that common variants in these genes have no impact in modifying MM risk. Table I. Genotype distribution of the PXR and CAR SNPs among MM cases and controls. SNP (rs) Cases (%) Controls (%) OR* 95%C.I. p-value p-trend PXR C/C 429 (69.5) 623 (70.7) 1.00 Ref 0.423 rs10511395 A/C 160 (25.9) 228 (25.9) 1.02 0.81 – 1.30 0.851 A/A 28 (4.6) 30 (3.4) 1.38 0.81 – 2.35 0.232 PXR C/C 452 (74.0) 656 (74.8) 1.00 Ref 0.451 rs1054190 C/T 137 (22.4) 200 (22.8) 1.00 0.78 – 1.28 0.993 T/T 22 (3.6) 21 (2.4) 1.56 0.84 – 2.88 0.155 PXR C/C 412 (65.9) 591 (67.2) 1.00 Ref 0.819 rs11917714 C/T 190 (30.4) 250 (28.5) 1.07 0.85 – 1.35 0.535 T/T 23 (3.7) 38 (4.3) 0.84 0.49 – 1.44 0.536 PXR C/C 223 (36.3) 296 (33.7) 1.00 Ref 0.126 rs12488820 C/T 289 (47.0) 407 (46.4) 0.93 0.74 – 1.18 0.574 T/T 103 (16.7) 175 (19.9) 0.79 0.58 – 1.06 0.119 PXR G/G 430 (69.6) 593 (67.4) 1.00 Ref 0.807 rs13071341 A/G 166 (26.9) 269 (30.6) 0.85 0.67 – 1.07 0.158 A/A 22 (3.5) 18 (2.0) 1.70 0.90 – 3.22 0.102 PXR A/A 352 (58.7) 516 (39.4) 1.00 Ref 0.981 rs3237359 A/G 209 (34.8) 291 (33.5) 1.04 0.83 – 1.30 0.720 G/G 39 (6.5) 62 (7.1) 0.90 0.59 – 1.37 0.619 PXR C/C 255 (41.2) 383 (43.6) 1.00 Ref 0.815 rs13059232 C/T 299 (48.3) 390 (44.4) 1.16 0.93 – 1.44 0.192 T/T 65 (10.5) 106 (12.0) 0.94 0.66 – 1.33 0.711 PXR A/A 300 (48.7) 437 (49.7) 1.00 Ref 0.258 rs3732357 A/G 240 (39.0) 361 (41.0) 0.94 0.75 – 1.17 0.589 G/G 76 (12.3) 82 (9.3) 1.31 0.92 – 1.85 0.130 PXR T/T 328 (53.6) 463 (52.9) 1.00 Ref 0.424 rs1357459 C/T 249 (40.7) 345 (39.4) 1.02 0.82 – 1.27 0.850 C/C 35 (5.7) 67 (7.7) 0.75 0.49 – 1.17 0.206 CAR A/A 218 (35.4) 335 (38.1) 1.00 Ref 0.571 rs3003596 A/G 296 (48.0) 393 (44.7) 1.16 0.93 – 1.46 0.191 G/G 102 (16.6) 151 (17.2) 1.04 0.77 – 1.41 0.799 CAR G/G 264 (42.7) 371 (42.0) 1.00 Ref 0.642 rs3813627 G/T 276 (44.7) 392 (44.4) 0.98 0.79 – 1.23 0.882 T/T 78 (12.6) 120 (13.6) 0.91 0.66 – 1.26 0.581 CAR A/A 441 (73.1) 635 (73.5) 1.00 Ref 0.911 rs11265571 A/T 147 (24.4) 207 (24.0) 1.01 0.79 – 1.29 0.911 T/T 15 (2.5) 22 (2.5) 0.97 0.49 – 1.89 0.921 CAR T/T 404 (64.2) 575 (65.7) 1.00 Ref 0.836 rs2307418 G/T 193 (31.1) 268 (30.6) 1.02 0.81 – 1.27 0.879 G/G 23 (3.7) 32 (3.7) 1.05 0.60 – 1.83 0.863 CAR C/C 348 (56.6) 508 (57.7) 1.00 Ref 0.527 rs2502805 C/T 220 (35.8) 313 (35.6) 1.05 0.84 – 1.30 0.693 T/T 47 (7.6) 59 (6.7) 1.16 0.77 – 1.74 0.484 CAR A/A 245 (39.8) 346 (39.4) 1.00 Ref 0.770 rs4073054 A/C 291 (47.2) 412 (46.9) 0.98 0.78 – 1.22 0.855 C/C 80 (13.0) 120 (13.7) 0.94 0.68 – 1.31 0.720 CAR C/C 360 (57.6) 524 (59.8) 1.00 Ref 0.391 rs4233368 A/C 225 (36.0) 302 (34.4) 1.09 0.88 – 1.36 0.439 A/A 40 (6.4) 51 (5.8) 1.15 0.74 – 1.78 0.538 Genotype distribution among MM cases and controls in the overall population. * OR are adjusted for age, gender and region of origin. Differences in samples numbers are due to failures in genotyping. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

The Chronic Kidney Disease-Epidemiology Collaboration-Cystatin C (CKD-EPI-CysC) Equation Has an Independent Prognostic Value for Overall Survival in Newly-Diagnosed Patients with Symptomatic Multiple Myeloma: Comparison with 3 Other Equations for GFR Estimation

Blood ◽

10.1182/blood.v120.21.1849.1849 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1849-1849

Author(s):

Meletios A Dimopoulos ◽

Efstathios Kastritis ◽

Eirini Katodritou ◽

Anastasia Pouli ◽

Eurydiki Michalis ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Cystatin C ◽

Prognostic Value ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

P Value ◽

Newly Diagnosed ◽

Number Of Patients ◽

Ckd Stage

Abstract Abstract 1849 Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The estimation of glomerular filtration rate (GFR) is based on equations that use serum creatinine (sCr) as a marker of RI (i.e. MDRD or CKD-EPI). The IMWG has recommended the use of the MDRD formula for the estimation of GFR in MM patients with stabilized sCr, while the classification of RI is based on the 5 stages of the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). However, the equations based on sCr are imprecise and thus novel markers of renal injury have been used in patients with renal damage, including cystatin-C (CysC). CysC is considered as a more sensitive marker of GFR than sCr. Recently, the CKD-EPI investigators have reported that a combined sCr-CysC (CKD-EPI-sCr-CysC) equation correlated better with GFR than equations based on either of these markers alone (CKD-EPI or CKD-EPI-CysC; Inker et al, NEJM 2012;367:20–9). Although cysC has been reported by our group to be elevated in MM patients, the CKD-EPI equations and their value on MM patients' survival have never been evaluated. Therefore, we studied 220 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years) and 16% had sCr ≥2 mg/dl. Serum CysC was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). Serum CysC was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, CKD-EPI, CKD-EPI-CysC and CKD-EPI-sCr-CysC equations were 63.45 ml/min/1.73m2, 68.13 ml/min/1.73m2, 68.11 ml/min/1.73 m2, and 64.87 ml/min/1.73 m2, respectively (p<0.01). Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 39.5% for MDRD vs. 42.2% for CKD-EPI vs. 43.1% for CKD-EPI-CysC vs. 45% for CKD-EPI-sCr-CysC (p<0.01; see also the table). Concordance for CKD stage allocation for the 4 equations of estimating eGFR was 97% for MDRD vs. CKD-EPI, 60% for MDRD vs. CKD-EPI-CysC and 84% for MDRD vs. CKD-EPI-sCr-CysC. A significant correlation was found between ISS stage and all studied equations (p<0.01 for all). The median overall survival (OS) for all patients was 52 months. In the univariate analysis per CKD stage, the 4 equations could predict for OS (the higher CKD stage had poorer survival) with the following significance: MDRD (p=0.057), CKD-EPI (p=0.01), CKD-EPI-CysC (p<0.0001), and CKD-EPI-sCr-CysC (p=0.006). When we tested the 4 equations as continuous variables, all had prognostic value for OS but the CKD-EPI-CysC had the strongest prognostic value (p<0.0001 and Wald=24.0 vs. p<0.0001 and Wald=19.7 for CKD-EPI-sCr-CysC, p=0.003 and Wald=8.9 for CKD-EPI and p=0.005 and Wald=7.7 for MDRD). In the multivariate analysis, that included ISS stage, LDH ≥300 U/l and eGFR for each different equation (as a continuous variable) only eGFR that included CysC but not sCr (CKD-EPI-CysC and not CKD-EPI-sCr-CysC) had independent significance (p=0.013) along with high LDH (p=0.029). Our data suggest that the CKD-EPI-sCr-CysC equation for the estimation of GFR detects more MM patients with stage 3–5 RI than the MDRD, CKD-EPI or CKD-EPI-CysC equations. However, CKD-EPI-CysC was the only equation that could predict for OS, possibly due to the very strong correlation of CysC with ISS (as myeloma cells produce CysC also). The confirmation of these data will lead to the broader use of equations based on CysC (CKD-EPI-CysC with or without sCr) for the evaluation of RI in patients with MM, as it has been suggested for patients with several other renal disorders. Table. Evaluation of Renal Function Stage by Different Equations CKD stage MDRD equation CKD-EPI equation CKD-EPI-CysC equation CKD-EPI-sCr-CysC equation p-value 1 60 (27%) 57 (26%) 67 (30%) 44 (20%) 2 73 (33%) 70 (32%) 58 (26%) 77 (35% Friedman-test 3 53 (24%) 55 (25%) 57 (26%) 62 (28%) p<0.01 4 21 (9.5%) 25 (11%) 27 (12%) 24 (11%) 5 13 (6%) 13 (6%) 11 (5%) 13 (6%) Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Bortezomib Induced Peripheral Neuropathy Is Related to Altered Level of Brain Derived Neurotrophic Factor in the Circulating Blood.

Blood ◽

10.1182/blood.v120.21.2819.2819 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2819-2819

Author(s):

David Azoulay ◽

David Lavie ◽

Moshe E. Gatt ◽

Celia Surio ◽

Luiza Akaria ◽

...

Keyword(s):

Multiple Myeloma ◽

Peripheral Neuropathy ◽

Neurotrophic Factor ◽

Hematological Malignancies ◽

Conflicts Of Interest ◽

Brain Derived Neurotrophic Factor ◽

P Value ◽

Limiting Factor ◽

Altered Level ◽

Bortezomib Treatment

Abstract Abstract 2819 Peripheral Neuropathy (PN) is a major side effect and dose-limiting factor of Bortezomib treatment in multiple myeloma (MM). The exact mechanism underlying Bortezomib induced PN (BIPN) is unknown, and the risk factors which increase susceptibility for developing this syndrome have yet to be elucidated. Brain Derived Neurotrophic Factor (BDNF) is a nerve growth factor which is responsible for the development, maintenance, and repair of the peripheral nervous system. Aim: In this work we examined alterations in the levels of BDNF in circulating blood and searched for their relation with BIPN development. Method: 24 patients with Multiple Myeloma receiving Bortezomib based regimen and 30 patients with other hematological malignancies (OHM) were examined. We used ELISA to quantify soluble BDNF (sBDNF) level in patient's platelets-poor plasma (PPP) and flow cytometry or western blotting to quantify BDNF in platelets. PN was assessed and graded according to the cancer common toxicity criteria index. Results: The level of sBDNF in MM patients PPP at diagnosis was similar to the level of sBDNF in patients with other hematological malignancies at diagnosis (3.86±2.47 ng/ml Mean ± SD in MM and 3.70±2.5 ng/ml in OHM). During treatment with Bortezomib the level of sBDNF was reduced only in the group of MM patients that developed BIPN (1.94±1.7 ng/ml P value<0.05) whereas the level of sBDNF in MM patients who did not develop BIPN remained equal to the level at diagnosis. Correspondingly, a negative correlation between the level of sBDNF and the severity of BIPN was observed. Analysis of platelets, the main cellular storage of BDNF in the peripheral blood, revealed a high incidence of BDNF-containing platelets as well as increased BDNF content within platelets of patients with BIPN as compared to patients without BIPN. No difference in the number of platelets between patients with BIPN and patients without BIPN was observed. Conclusions: Our results suggest that alterations in the circulating blood level of BDNF may play role in the pathophysiology of BIPN development. Detailed investigation regarding potential mechanisms by which BDNF is involved in BIPN is required. Furthermore, BDNF could serve as a useful biomarker for early detection of Bortezomib induced BIPN. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Mucin-1 (MUC1) Oncoprotein in Multiple Myeloma Cells Inhibits the Th1 Responses By Down Regulating the Expression of Mir-200c and up-Regulating the PDL1 Expression

Blood ◽

10.1182/blood.v124.21.2072.2072 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2072-2072 ◽

Cited By ~ 1

Author(s):

Hasan Rajabi ◽

Maxwell Douglas Coll ◽

Jacalyn Rosenblatt ◽

Li Yin ◽

Dina Stroopinsky ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Cell Lines ◽

Immune Escape ◽

Conflicts Of Interest ◽

Ectopic Expression ◽

Micro Rna ◽

P Value ◽

Muc1 Expression ◽

Myeloma Cells

Abstract Introduction: The PDL1/PD-1 pathway is a critical mediator of immune escape in patients with multiple myeloma (MM). Regulation of this pathway has not been well characterized. MicroRNAs (miRNAs) are a conserved class of small (~22 nucleotides) RNAs that post-transcriptionally regulate gene expression by interacting with the 3′ untranslated region (3′ UTR) and, in some settings, coding regions of target mRNAs. MiRNAs suppress gene expression by promoting mRNA degradation or inhibiting translation. Of note, the 3’UTR of the PDL1 gene contains putative binding sites for miR-200 family of micro-RNA’s, suggesting a possible role of miR-200’s in regulation of PDL1 expression. We have previously demonstrated that miR-200c is suppressed by the MUC1 oncoprotein, and hypothesized that MUC1 expression on myeloma cells upregulates the expression of PDL1, via suppressing miR-200c. In the present study, we investigated the relationship between MUC1, miR-200c and PDL1 in multiple myeloma. Methods and Results: Lentivirus vectors expressing miR-200c or a control vector with green fluorescence protein (GFP) were transduced in two different MM cell lines (MM-RPMI, MM-U266). Cells were harvested sorted by Fluorescence-Activated Cell Sorting (FACS) after 72 hours of transduction, using a dual fluorescence for GFP and anti-PDL1 antibody to analyze the changes in PDL1 expression. MiR-200c transduction of U266 cells resulted in a decrease in mean expression of PDL1 from 69.55% to 1.4% (n=2). Similarly, RPMI cells demonstrated a reduction in mean expression of PDL1 from 62.5% to 1.9% (n=2) following miR-200c transduction. The abrogation of PDL1 expression in MM cells by ectopic expression of miR-200c was confirmed using western immunoblot analysis. Having previously demonstrated that miR-200c is suppressed by MUC1 in a solid tumor model, we evaluated the effect of silencing MUC1 in U266 and RPMI cell lines on miR-200c and PDL1 expression. MUC1 silenced stable cell lines of RPMI and U266 cells were generated using lentivirus shRNA vectors against MUC1 or a scrambled vector control. MUC1 silenced cells demonstrated an increase in miR-200c expression (> 2 fold, p value <0.05). Notably, PDL1 expression decreased from 52% to 3.7% and from 62.5% to 6.1% following silencing of MUC1 on U266 and RPMI cells respectively. Conclusions: Ectopic expression of micro-RNA miR-200c in RPMI-MM and U266-MM cell lines results in down regulation of PDL1 expression. Silencing MUC1 in RPMI-MM and U266-MM cell lines results in both increased expression of miR-200c and downregulation of PDL1 expression. These results support the hypothesis that MUC1 expression on myeloma cells contributes to tumor mediated immunosuppression, by suppressing miR-200c thereby enhancing PDL1 expression. Interfering with MUC1 mediated signaling represents a novel approach towards augmenting immune mediated targeting of myeloma. Disclosures No relevant conflicts of interest to declare.

Download Full-text

LACK of ASSOCIATION BETWEEN Race and Probability of TRANSPLANT AMONG PATIENTS Referred for Hematopoietic CELL TRANSPLANTATION (HCT) for MULTIPLE Myeloma

Blood ◽

10.1182/blood.v118.21.3129.3129 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3129-3129

Author(s):

Manish Sharma ◽

Michael Bromberg ◽

Thomas R. Klumpp ◽

Patricia Kropf ◽

Mary Ellen Martin ◽

...

Keyword(s):

Multiple Myeloma ◽

African American ◽

Hematopoietic Cell Transplantation ◽

Conflicts Of Interest ◽

P Value ◽

Initial Visit ◽

Transplant Center ◽

Caucasian Patients ◽

Race 4 ◽

Median Interval

Abstract Abstract 3129 Background: As documented in recently published large database reviews, race appears to be a barrier to the access to HCT. Hypotheses as to why this may be the case include (but are not limited to): 1. patient preference; 2. delayed time to referral from community physicians to transplant centers; 3. delays in transplant once evaluated by a transplant center; 4. Possible increased prevalence of comorbidities among racial minorities referred for transplant. We attempt to address some of these issues by reviewing our 20-year experience with transplantation for multiple myeloma. Methods: We queried our core clinical database for potential associations between race and the following parameters: 1. Median interval between date of diagnosis and date of referral; 2. Median interval between date of initial visit and date of transplant 3. Probability of actually receiving a transplant following formal evaluation by a transplant physician by race; 4. Type of transplant recommended 5. Reasons for not receiving a transplant. Results: Between January 1990 and June 2011, 441 patients with multiple myeloma were referred to our center for consideration of HCT, of whom 293 (66%) were Caucasian, 94 (21%) were African American (AA), 27 (6%) were of unknown race, and 27 (6%) were of other races. The median interval from diagnosis to referral for transplant for AA patients was 145 days, versus 137 days for Caucasian patients (p=0.32). Fifty-three of the 94 AA patients (56%), versus 157 of the 293 Caucasian patients (54%) have received at least one transplant to date (p=0.72). The median interval between the date of the initial visit to our transplant center and the occurrence of an initial transplant was 120 days for AA, versus 150 days for Caucasians (p=0.39). The probability of being transplanted on an allogeneic or hybrid (auto-allo) initial transplant protocol was 0% for AA making it to transplant vs 6% for Caucasions making it to transplant (p=0.07). Reasons for not receiving a transplant are indicated in Table 1 (global p-value = 0.94). Conclusions: African American and Caucasian patients with myeloma have similar intervals from diagnosis to referral, similar intervals from referral to transplant, and are equally likely to actually receive a transplant once referral to the transplant center took place. Therefore, the reported barrier to transplantation for myeloma patients appears to be prior to referral to the transplant center. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Lymphocytopenia Is Associated with an Increased Risk of Severe Infections in Patients with Multiple Myeloma Treated with Bortezomib-Based Regimens

Blood ◽

10.1182/blood.v120.21.5042.5042 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5042-5042 ◽

Cited By ~ 1

Author(s):

Sung-Hoon Jung ◽

Jae-Sook Ahn ◽

Seung-Ji Kang ◽

Deok-Hwan Yang ◽

Yeo-Kyeoung Kim ◽

...

Keyword(s):

Multiple Myeloma ◽

Multivariate Analysis ◽

Conflicts Of Interest ◽

Severe Infection ◽

Infectious Complications ◽

P Value ◽

Factors Affecting ◽

Increased Risk ◽

Severe Infections ◽

Grade 3

Abstract Abstract 5042 Bortezomib is a proteasome inhibitor with potent antimyeloma activity in relapsed/refractory multiple myeloma (MM) patients. We evaluated the type and factors affecting the onset of infectious complications and mortality owing to infection in MM patients treated with bortezomib-based regimens. We reviewed 139 patients with MM treated with regimens containing bortezomib in order to assess the type and factors affecting the development of severe infections. Infections occurred in 56 (40. 3%) of 139 patients and 83 (7. 8%) cases of the 1, 069 evaluable cycles. Severe infections developed in 43 (30. 9%) patients and ten patients (7. 1%) died during bortezomib-based treatment. Multivariate analysis determined lymphocytopenia grade 3–4 (OR 3. 17, 95% CI 1. 38–7. 31, p = 0. 007) and number of cycle ° Â 8 cycles (OR 3. 91, 95% CI 1. 39–11. 02, p =0. 010) as risk factors associated with increased severe infection. This study showed that MM patients who received bortezomib-based regimens are at a higher risk of severe infections within eight cycles of treatment during especially severe lymphocytopenic period. MM patients treated with bortezomib-based regimens should be closely monitored for the development of infectious complications during lymphocytopenia. Table I. Multivariate analysis of factors affecting severe infection development Parameter OR (95% CI) p-Value Age (> 65) 1.78 (0.77–4.13) 0.180 Immunophenotype IgA 1.51 (0.60–3.77) 0.379 Lymphocytopenia (grade 3–4) 3.17 (1.38–7.31) 0.007 Neutropenia (grade 3–4) 1.25 (0.55–2.85) 0.600 Number of cycles (°Â 8 cycles) 3.91 (1.39–11.02) 0.010 Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Impact of a Patient-Access Program with Integrated Distress Screening on Resource Utilization and Psychosocial Distress Levels in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.1319.1319 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1319-1319

Author(s):

Victoria Kennedy ◽

Joanne S. Buzaglo ◽

Sara Goldberger

Keyword(s):

Multiple Myeloma ◽

Psychosocial Distress ◽

Patient Access ◽

Distress Screening ◽

Grant Funding ◽

Unrestricted Grant ◽

Cancer Support ◽

Distress Level ◽

Screening Questions ◽

Level Of Concern

Abstract Background: There is growing awareness of the importance in integrating psychosocial care into routine practice in oncology. A new American College of Surgeons Commission on Cancer accreditation standard requires psychosocial distress screening for patients with cancer as part of an initiative to treat the “whole patient” and ensure quality care. Distress screening at pivotal transition points along the disease continuum can identify problems before a crisis event occurs, allow patients to voice concerns and gain information, and improve the use of healthcare resources. The value of distress screening in patients with multiple myeloma (MM) or by industry patient access programs, however, has received relatively little attention to date. The Cancer Support Community (CSC), in collaboration with Onyx Pharmaceuticals, Inc., an Amgen subsidiary, established an integrated patient assistance program (Onyx 360) to screen and refer patients/caregivers facing advanced MM for psychosocial services. As part of this program, distress screening was performed at baseline and after patients engaged with Onyx 360 resources. Herein, we report results evaluating the impact of distress screening on the utilization of resources offered by Onyx 360 and the effect of these resources on patient distress levels over time. Methods: The Onyx 360 program was initiated in 2012 and distress screening was introduced in the program in late December 2013. Patients are asked 4 distress screening questions by an Onyx 360 Oncology Nurse Advocate during an initial phone call: 1.) overall level of distress today; 2.) level of concern about practical issues such as home care, transportation, finances, etc.; 3.) level of concern about family, work, or home life; and 4.) level of concern about emotional issues or coping with MM. For each question, patients gauged their level of distress on a scale from 0 to 10 (0-lowest level of distress and 10-highest level of distress). Patients were then offered enrollment in Onyx 360 services, which include reimbursement and clinical support, transportation assistance, and real-time referrals to key resources including the Chronic Disease Fund, the International Myeloma Foundation, the Multiple Myeloma Research Foundation, and the Cancer Support Community. Consenting patients/caregivers were transferred to CSC, whose licensed mental health professionals conducted further distress screening and offered patients/caregivers free supportive counseling, resource referral, group support, and treatment decision counseling. Patients were rescreened with the 4 questions 30 days after the initial call. Results: Between March 4, 2014 and July 11, 2014, a total of 227 patients in the Onyx 360 program were screened for baseline distress levels. For each screening question, 70%–80% of patients expressed some level of distress (i.e., distress level of ≥1). A total of 172 patients (76%) responded with a distress level of ≥4 for ≥1 of the screening questions; of these patients who were also new to Onyx 360 at the time of the initial call, 86% subsequently enrolled in ≥1 Onyx 360 service including 72% enrolling in transportation services and 27% enrolling in copay assistance. Referral rates to the CSC increased when distress screening was performed compared with when it was not. A total of 145 (64%) patients completed a follow-up call; 74% reported lower levels of distress for ≥1 question since the initial call. Among patients who initially reported a distress level of ≥4 on ≥1 of the screening questions, 79% reported lower levels of distress for ≥1 question since the initial call. Conclusion: Through a brief distress screening measure, the Onyx 360 program identified patients with psychosocial distress and connected them to a variety of resources and community programs. Patients utilized these resources at a higher rate when distress screening was implemented compared with when it was not. Distress levels decreased after patients engaged with these resources and services; moreover, the decrease in distress levels was greatest in patients who initially had higher levels of distress. These results demonstrate that an integrated patient-centered standard of care improves psychosocial outcomes in patients with advanced MM. Further research is needed to determine whether reduced levels of distress will translate into increased duration of therapy and increase in value to the patient and healthcare system. Disclosures Kennedy: Onyx Pharmaceuticals: Unrestricted grant funding Other. Buzaglo:Onyx Pharmaceuticals: Unrestricted grant funding Other. Goldberger:Onyx Pharmaceuticals: Unrestricted grant funding Other.

Download Full-text

Treatment Advances for Multiple Myeloma Have Disproportionally Benefited Patients Who Are Young, White, and Have Higher Socioeconomic Status

Blood ◽

10.1182/blood.v124.21.555.555 ◽

2014 ◽

Vol 124 (21) ◽

pp. 555-555 ◽

Cited By ~ 1

Author(s):

Mark A. Fiala ◽

Jesse Keller ◽

Keith E. Stockerl-Goldstein ◽

Michael H. Tomasson ◽

Ravi Vij ◽

...

Keyword(s):

Multiple Myeloma ◽

Socioeconomic Status ◽

Overall Survival ◽

Conflicts Of Interest ◽

Age At Diagnosis ◽

Reference Level ◽

P Value ◽

Cox Regression Analysis ◽

Black Patients ◽

White Patients

Abstract Background: The use of autologous stem cell transplants (ASCT) for multiple myeloma (MM) has greatly improved overall survival (OS), however, not all patients have benefited equally. Several studies have indicated that patients over the age of 65 or 70 at diagnosis had no immediate improvement in OS following the use of ASCT for MM, which is intuitive as ASCT was not covered by Medicare until 2001 and today is still often reserved for patients under 70. In addition, Waxman, et al (Blood, 2010) reported that ASCT for MM, resulted in nearly a two-fold improvement in OS in white patients compared to black patients. This suggests that white patients had better access to ASCT as retrospective studies of MM patients who undergo ASCT have failed to show an OS difference between the two races. Disparities in the OS benefit of ASCT among patients of different socioeconomic groups have not been reported on to date. It is also unclear if these disproportional improvements in outcomes have continued following the approvals of bortezomib and lenalidomide. Methods: Using the SEERStat software, we extracted the case listings of 85,115 patients diagnosed with MM from 1973 through 2010 in Surveillance Epidemiology and End Results (SEER)-18 registries database based on the November 2012 submission. Children (under 18 years old) were excluded. Autopsy or death certificate only cases were excluded. Patients identified as any race other than white or black were excluded. Patients were followed for OS through December 2011. Patients were divided into three cohorts based on the year of diagnosis, era 1 those diagnosed from 1973 to 1994, era 2 those diagnosed from 1995-2002 (to coincide with ASCT), and era 3 those diagnosed from 2003-2010 (to coincide with bortezomib’s approval). Socioeconomic status (SES) was approximated by median household income (MHI) of each patient’s county of residence from the 1990 US census; patients were divided into tertiles within their era of diagnosis based on MHI and classified as low-SES, middle-SES, or high-SES. Results: 78,681 patients were eligible for analysis. The median age at diagnosis was 70 years (range 18-85+); 54% were male; 18% were black. The median follow-up was 22 months (range 0-441). The OS of white patients increased from 23 months in the era 1 to 27 months in era 2, to 36 months in the era 3 (p <0.001), representing improvements 15% and 25%, respectively; the OS of black patients increased from 27 months to 28 months to 36 months (p <0.001), representing only improvements of 4% and 22% respectively. In patients under 65 years old at diagnosis, those most likely to be candidates for ASCT, the OS of white patients increased from 35 months in era 1 to 52 months in era 2, to 69 months in era 3 (p <0.001), representing improvements 33% and 25%, respectively; the OS of black patients increased from 36 months to 41 months to 58 months (p <0.001), representing improvements of 12% and 29% respectively. During era 1 being younger and/or being black were both independently associated with improved OS while SES was not associated with OS. In era 2 and era 3 being younger, being white, and/or being higher SES were all independently associated with improved OS. Table 1 summarizes the results from the multivariate cox regression analysis. Table 1- Multivariate Overall Survival Analysis Era 1 (1973-1994) Era 2 (1995-2002) Era 3 (2003-2010) Age HR1 (95% CI) p value HR1 (95% CI) p value HR1 (95% CI) p value <65 12 12 12 65-69 1.32 (1.27-1.38) < 0.001 1.48 (1.41-1.55) < 0.001 1.37 (1.31-1.45) < 0.001 70+ 1.85 (1.80-1.91) < 0.001 2.26 (2.19-2.34) < 0.001 2.56 (2.47-2.64) < 0.001 Race White 12 12 12 Black 0.95 (0.91-0.98) 0.005 1.05 (1.01-1.09) 0.008 1.04 (1.01-1.08) 0.025 SES High 12 12 12 Middle 0.98 (0.95-1.01) 0.230 1.08 (1.04-1.12) < 0.001 1.14 (1.10-1.18) < 0.001 Low 1.01 (0.98-1.04) 0.662 1.13 (1.09-1.17) < 0.001 1.22 (1.17-1.26) < 0.001 1- Hazard Ratio is adjusted for all other variables within the model 2- Used as the Reference level Conclusions: As previously reported, the improvements in OS following the use of ASCT for MM disproportionally benefited patients who were a younger age at diagnosis and/or were white. In addition, higher SES patients benefited more than lower SES, a novel finding. Bortezomib and lenalidomide have equally benefited both black and white patients, but has worsened the outcome disparities for patients over 70 years of age at diagnosis and/or those with lower SES. Disclosures No relevant conflicts of interest to declare.

Download Full-text