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https://www.readbyqxmd.com/read/28892086/allogeneic-stem-cell-transplantation-and-subsequent-treatments-as-a-comprehensive-strategy-for-long-term-survival-of-multiple-myeloma-patients
#1
V Montefusco, A Mussetti, F Rezzonico, F Maura, M Pennisi, C de Philippis, M Capecchi, P Corradini
We evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma (MM). Forty-three patients (61%) received allo-HCT after the first line of therapy. Fifty-eight patients (82%) had chemosensitive disease at the time of allo-HCT. A HLA-matched related or unrelated donor was available for 68 patients (96%). Non-myeloablative or reduced-intensity conditioning regimen and peripheral blood hematopoietic cells as a graft source were used in most patients. The cumulative incidence of grade II-IV acute GVHD at day +100 and chronic GVHD at 5 years was 13% (95% CI 7-23%) and 35% (95% CI 24-46), respectively...
September 11, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28883264/treatment-algorithms-for-multiple-myeloma-in-japan
#2
Shuji Ozaki
Recent progress in the development of novel therapeutic agents has remarkably improved the treatment outcome for multiple myeloma (MM). Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib; immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide; the histone deacetylase (HDAC) inhibitor panobinostat; and the monoclonal antibody, elotuzumab, have all been approved in Japan, although only bortezomib and lenalidomide have been approved for initial therapy. Accordingly, the Japanese Society of Hematology has released updated treatment guidelines for MM...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28881567/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpes-virus-infected-cells-by-lenalidomide-and-pomalidomide
#3
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874903/pomalidomide-desensitization-in-a-patient-hypersensitive-to-immunomodulating-agents
#4
J T Seki, N Sakurai, W Lam, D E Reece
Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published)...
August 2017: Current Oncology
https://www.readbyqxmd.com/read/28863804/investigation-of-a-gene-signature-to-predict-response-to-immunomodulatory-derivatives-for-patients-with-multiple-myeloma-an-exploratory-retrospective-study-using-microarray-datasets-from-prospective-clinical-trials
#5
Manisha Bhutani, Qing Zhang, Reed Friend, Peter M Voorhees, Lawrence J Druhan, Bart Barlogie, Pieter Sonneveld, Gareth J Morgan, James T Symanowski, Belinda R Avalos, Edward A Copelan, Saad Z Usmani
BACKGROUND: Immunomodulatory derivatives (IMiDs), along with proteasome inhibitors, are key components of treatment regimens for multiple myeloma. Nonetheless, outcomes vary among treated individuals. Drug-specific gene-expression profile (GEP) signatures that aid the prediction of favourable and unfavourable outcomes can provide patients with the most effective therapy for their individual disease. We aimed to develop and validate a gene expression signature to suggest which patients would benefit most from IMiD-based therapies...
September 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28860711/pomalidomide-in-the-treatment-of-multiple-myeloma-design-development-and-place-in-therapy
#6
REVIEW
Rafael Ríos-Tamayo, Agustín Martín-García, Carolina Alarcón-Payer, Dolores Sánchez-Rodríguez, Ana María Del Valle Díaz de la Guardia, Carlos Gustavo García Collado, Alberto Jiménez Morales, Manuel Jurado Chacón, José Cabeza Barrera
Multiple myeloma is a very heterogeneous disease with variable survival. Despite recent progress and the widespread use of new agents, patients with relapsed and refractory disease have a poor outcome. Immunomodulatory drugs play a key role in both the front-line and the relapsed/refractory setting. The combination of pomalidomide (POM) and dexamethasone is safe and effective in relapsed and refractory patients, even in those with high-risk cytogenetic features. Furthermore, it can be used in most patients without the need to adjust according to the degree of renal failure...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28860655/pomalidomide-dexamethasone-in-refractory-multiple-myeloma-long-term-follow-up-of-a-multi-cohort-phase-ii-clinical-trial
#7
S Ailawadhi, J R Mikhael, B R LaPlant, K M Laumann, S Kumar, V Roy, D Dingli, P L Bergsagel, F K Buadi, S V Rajkumar, R Fonseca, M A Gertz, P Kapoor, T Sher, S R Hayman, A K Stewart, A Dispenzieri, R A Kyle, W I Gonsalves, C B Reeder, Y Lin, R S Go, N Leung, T Kourelis, J A Lust, S J Russell, A A Chanan-Khan, M Q Lacy
Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were 3 with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs...
September 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28860344/the-kinesin-spindle-protein-inhibitor-filanesib-enhances-the-activity-of-pomalidomide-and-dexamethasone-in-multiple-myeloma
#8
Susana Hernández-García, Laura San-Segundo, Lorena González-Méndez, Luis A Corchete, Irena Misiewicz-Krzeminska, Montserrat Martín-Sánchez, Ana-Alicia López-Iglesias, Esperanza-Macarena Algarín, Pedro Mogollón, Andrea Díaz-Tejedor, Teresa Paíno, Brian Tunquist, María-Victoria Mateos, Norma C Gutiérrez, Elena Díaz-Rodriguez, Mercedes Garayoa, Enrique M Ocio
Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor if this proteins, has demonstrated activity in heavily pretreated multiple myeloma patients. The aim of this work was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect.The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in several in vitro and in vivo models...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28844714/up-regulation-of-olr1-expression-by-tbc1d3-through-activation-of-tnf%C3%AE-nf-%C3%AE%C2%BAb-pathway-promotes-the-migration-of-human-breast-cancer-cells
#9
Bei Wang, Huzi Zhao, Lei Zhao, Yongchen Zhang, Qing Wan, Yong Shen, Xiaodong Bu, Meiling Wan, Chuanlu Shen
Metastatic spread of cancer cells is the most life-threatening aspect of breast cancer and involves multiple steps including cell migration. We recently found that the TBC1D3 oncogene promotes the migration of breast cancer cells, and its interaction with CaM enhances the effects of TBC1D3. However, little is known regarding the mechanism by which TBC1D3 induces the migration of cancer cells. Here, we demonstrated that TBC1D3 stimulated the expression of oxidized low density lipoprotein receptor 1 (OLR1), a stimulator of cell migration, in breast cancer cells at the transcriptional level...
August 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28840598/therapeutic-monoclonal-antibodies-in-combination-with-pomalidomide-can-overcome-refractoriness-to-both-agents-in-multiple-myeloma-a-case-based-approach
#10
Marc-Andrea Baertsch, Michael Hundemer, Jens Hillengass, Hartmut Goldschmidt, Marc S Raab
In multiple myeloma (MM), the synergy between immunomodulatory drugs (IMiDs) and monoclonal antibodies (MABs) has been demonstrated in several pivotal trials. However, disease refractory to either class of compounds remains a major therapeutic challenge. We here report on 3 heavily pretreated MM patients who were refractory to pomalidomide as well as to MABs against CD38 (daratumumab) or CD20 (rituximab), respectively, but who responded to retreatment with the same agents in combination. Responses were durable with PFS of 7, 10 (ongoing), and 30 months from initiation of combination treatment...
August 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28819377/effect-of-pomalidomide-on-relapsed-refractory-multiple-myeloma-a-systematic-review-and-meta-analysis
#11
Runzhe Chen, Yujie Wang, Chengxin Luan, Chong Gao, Xiaoping Zhang, Baoan Chen
In this work, we aim to further analyze the effect of pomalidomide for relapsed and/or refractory multiple myeloma (RRMM). A systematic literature search of PubMed, MEDLINE and EMBASE was conducted on September 20, 2016. Pooled effect size (ES) with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA software (version 12.0; Stata Corporation; College Station, TX, USA) was employed to do all statistical analyses. A total of 8 studies were included for analysis. The combined results demonstrated that the pooled proportion of overall response rate (ORR) was 0...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28799436/immunotherapy-based-approaches-in-myelofibrosis
#12
Lucia Masarova, Srdan Verstovsek, Hagop Kantarjian, Naval Daver
Aberrant regulation of the immune system with up-regulation of pro-inflammatory cytokines contributes to disease pathophysiology in myelofibrosis (MF). Therapeutic options for MF associated anemia, thrombocytopenia, and bone marrow fibrosis remain limited. Areas covered: This review focuses on immune based therapies in MF, including immunomodulatory imide drugs (IMiDs), interferons, monoclonal antibodies and targeted agents (SL-401), and checkpoint inhibitors. Published literature was reviewed using available databases (PubMed, Cochrane, Scopus) and web pages (clinicaltrials...
August 22, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28799231/efficacy-of-daratumumab-based-therapies-in-patients-with-relapsed-refractory-multiple-myeloma-treated-outside-of-clinical-trials
#13
Arjun Lakshman, Jithma P Abeykoon, Shaji K Kumar, S Vincent Rajkumar, David Dingli, Francis K Buadi, Wilson I Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V Kourelis, Ronald S Go, Martha Q Lacy, Miriam A Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L Fonder, Yi L Hwa, Suzanne R Hayman, Stephen J Russell, Robert A Kyle, Morie A Gertz, Prashant Kapoor
Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4...
August 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28790111/amiloride-an-old-diuretic-drug-is-a-potential-therapeutic-agent-for-multiple-myeloma
#14
Elizabeta Rojas, Luis Corchete, Laura San Segundo, Juan F Martínez-Blanch, Francisco M Codoñer, Teresa Paíno, Noemi Puig, Ramón García-Sanz, Maria Victoria Mateos, Enrique M Ocio, Irena Misiewicz-Krzeminska, Norma C Gutiérrez
<br />The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.<br /><br />Experimental Design:  <p>Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq, qRT-PCR, immunoblotting and immunofluorescence assays...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28763310/elderly-patients-with-multiple-myeloma-towards-a-frailty-approach
#15
REVIEW
Sonja Zweegman, Monika Engelhardt, Alessandra Larocca
PURPOSE OF REVIEW: To describe how to better identify frail multiple myeloma patients and to treat them appropriately. RECENT FINDINGS: Proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, and immunomodulatory agents (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, have significantly improved the outcome of multiple myeloma patients in the last decade. However, both in clinical trials and in daily clinical practice, elderly multiple myeloma patients have shown lesser benefit...
September 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28747580/emerging-drugs-and-combinations-to-treat-multiple-myeloma
#16
REVIEW
Alessandra Larocca, Roberto Mina, Francesca Gay, Sara Bringhen, Mario Boccadoro
In the past few years, multiple targeted therapies and immunotherapies including second generation immunomodulatory drugs (pomalidomide) and proteasome inhibitors (carfilzomib, ixazomib), monoclonal antibodies and checkpoint inhibitors were approved for the treatment of myeloma or entered advanced phases of clinical testing. These agents showed significant activity in advanced myeloma and increased the available treatment strategies.Pomalidomide is well-tolerated and effective in patients with relapsed/refractory multiple myeloma who have exhausted any possible treatment with lenalidomide and bortezomib...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747306/how-i-treat-new-agents-in-myeloma
#17
Philippe Moreau
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs) and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second generation PIs carfilzomib and ixazomib, the DACI panobinostat and two monoclonal antibodies, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines and have transformed our approach to the treatment of patients...
July 26, 2017: Blood
https://www.readbyqxmd.com/read/28723635/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#18
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700354/docking-of-cdk1-with-antibiotic-drugs-revealed-novel-therapeutic-value-in-breast-ductal-cancer-in-situ
#19
Zhong-Hai Ding, Jia Qi, An-Quan Shang, Yu-Jie Zhang, Jun Wei, Li-Qing Hu, Wei-Wei Wang, Man Yang
The aim of our research is to identify potential genes associated with Ductal carcinoma in situ (DCIS) through microarrays. The microarray dataset GS54665 were downloaded from the GEO(Gene Expression Omnibus) database. Dysregulated genes were screened and their associations with DCIS was analyzed by comprehensive bioinformatics tools. A total of 649 differential expression genes were identified between normal and DCIS samples, including 224 up-regulated genes and 425 down-regulated genes. Biological process annotation and pathway enrichment analysis identified several DCIS-related signaling pathways...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28684537/pomalidomide-bortezomib-and-dexamethasone-pvd-for-patients-with-relapsed-lenalidomide-refractory-multiple-myeloma
#20
Jonas Paludo, Joseph R Mikhael, Betsy R LaPlant, Alese E Halvorson, Shaji Kumar, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Angela Dispenzieri, John A Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David Dingli, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rafael Fonseca, P Leif Bergsagel, Vivek Roy, Taimur Sher, Asher A Chanan-Khan, Sikander Ailawadhi, A Keith Stewart, Craig B Reeder, Paul G Richardson, S Vincent Rajkumar, Martha Q Lacy
This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m(2) IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 given every 28 days. Bortezomib was increased to 1.3 mg/m(2) for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients...
July 6, 2017: Blood
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