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https://www.readbyqxmd.com/read/28431262/immunologic-approaches-for-the-treatment-of-multiple-myeloma
#1
REVIEW
Leo Rasche, Niels Weinhold, Gareth J Morgan, Frits van Rhee, Faith E Davies
The FDA approval of two monoclonal antibodies in 2015has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, 'off-target' immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies...
April 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28428898/severe-acute-hepatitis-b-in-hbv-vaccinated-partner-of-a-patient-with-multiple-myeloma-treated-with-cyclophosphamide-bortezomib-and-dexamethasone-and-autologous-stem-cell-transplant
#2
Majed M Almaghrabi, Kyle J Fortinsky, David Wong
Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28416150/stem-cell-transplantation-in-multiple-myeloma
#3
Manjulika Das
No abstract text is available yet for this article.
April 13, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28411174/evaluation-of-hematopoietic-stem-cell-mobilization-rates-with-early-plerixafor-administration-time-for-adult-stem-cell-transplantation
#4
Jessica T Stover, J Ryan Shaw, Maragatha Kuchibhatla, Mitchell E Horwitz, Ashley M Engemann
The addition of plerixafor to high-dose colony stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin's lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the FDA approved administration time of 11 hours prior to apheresis and an earlier administration time of 16 hours prior to apheresis. Medical records of patient ≥ 18 years of age undergoing autologous stem cell transplantation requiring the use of plerixafor after at least four days of G-CSF therapy to complete stem cell mobilization from 1 January 2010 through 30 September 2014 were retrospectively reviewed...
April 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28409228/diagnosis-and-treatment-of-multiple-myeloma-in-germany-analysis-of-a-nationwide-multi-institutional-survey
#5
Maximilian Merz, Lenka Kellermann, Wolfram Poenisch, Hans-Joachim Tischler, Joern Kohnke, Wolfgang Knauf, Hartmut Goldschmidt
A nationwide, multi-institutional survey was performed in 2011 and 2015 to analyze routine practice for myeloma patients outside clinical trials in Germany. We contacted university hospitals, community hospitals, and office-based hematologists in order to enter clinical data from newly diagnosed and relapsed patients into an online platform. Complete datasets were available for 478 (2011) and 515 (2015) patients. While median age at diagnosis increased from 70 to 72 years, patients had fewer concomitant diseases (2011 61%; 2015 51%) and presented with equal performance status (ECOG 0-1, 2011 66%; 2015 68%)...
April 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28402945/a-prospective-open-label-multicenter-observational-study-to-evaluate-the-efficacy-and-safety-of-bortezomib-melphalan-prednisone-as-initial-treatment-for-autologous-stem-cell-transplantation-ineligible-patients-with-multiple-myeloma
#6
Min Kyoung Kim, Kihyun Kim, Chang-Ki Min, Jae-Yong Kwak, Sang-Byung Bae, Sung-Soo Yoon, Je-Jung Lee, Ki Hwan Kim, Seung-Hyun Nam, Yeung-Chul Mun, Hyo Jung Kim, Sung Hwa Bae, Ho-Jin Shin, Jung-Hee Lee, Joon Seong Park, Seong Hyun Jeong, Mark Hong Lee, Yang-Soo Kim, Ho Sup Lee, Keon Woo Park, Won-Sik Lee, Sang Min Lee, Jeong-Ok Lee, Myung Soo Hyun, Deog Yeon Jo, Sung-Nam Lim, Jae Hoon Lee, Do-Yeun Cho, Young Rok Do, Jeong-A Kim, Seong Kyu Park, Jin Seok Kim, Soo-Jeong Kim, Hawk Kim, Hyeon Gyu Yi, Joon Ho Moon, Chul Won Choi, Sung-Hyun Kim, Young-Don Joo, Hoon-Gu Kim, Byung Soo Kim, Moo-Rim Park, Moo-Kon Song, Su-Youn Kim
Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399522/autologous-stem-cell-transplantation-in-multiple-myeloma-in-the-era-of-novel-drug-induction-a-retrospective-single-center-analysis
#7
Gabriela B Thoennissen, Dennis Görlich, Ulrike Bacher, Thomas Aufenberg, Anne-Christin Hüsken, Anna Antonia Hansmeier, Georg Evers, Jan-Henrik Mikesch, Fleur Fritz, Carsten Bokemeyer, Carsten Müller-Tidow, Matthias Stelljes, Rolf M Mesters, Utz Krug, Martin H Kropff, Nils H Thoennissen, Wolfgang E Berdel
Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0...
April 12, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28383130/clinical-characteristics-and-prognostic-factors-in-multiple-myeloma-patients-with-light-chain-deposition-disease
#8
Meera Mohan, Amy Buros, Pankaj Mathur, Neriman Gokden, Manisha Singh, Sandra Susanibar, Jorge Jo Kamimoto, Shadiqul Hoque, Muthukumar Radhakrishnan, Aasiya Matin, Cynthia Davis, Monica Grazziutti, Sharmilan Thanendrarajan, Frits van Rhee, Maurizio Zangari, Faith Davies, Gareth Morgan, Joshua Epstein, Bart Barlogie, Carolina Schinke
Light chain deposition disease (LCDD) is characterized by monotypic immunoglobulin depositions which will eventually lead to loss of organ function if left untreated. While the kidney is almost always affected, the presence and degree of LCDD in other organs vary. Ten to 30% of LCDD patients have underlying Multiple Myeloma (MM), yet outcome and prognostic markers in this particular patient group are still lacking. Here, we analyzed 69 patients with MM and biopsy proven LCDD and report on renal and extra-renal involvement and its impact on prognosis as well as renal response depending on hematologic response...
April 6, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28382618/effects-of-single-agent-bortezomib-as-post-transplant-consolidation-therapy-on-multiple-myeloma-related-bone-disease-a-randomized-phase-ii-study
#9
Orhan Sezer, Meral Beksac, Roman Hajek, Gülsan Sucak, Seckin Cagirgan, Werner Linkesch, Olga Meltem Akay, Zafer Gülbas, Hareth Nahi, Torben Plesner, John A Snowden, Ayşen Timurağaoğlu, Tobias Dechow, Alois Lang, Tülin Tuğlular, Johannes Drach, Gabriele Armbrecht, Anna Potamianou, Catherine Couturier, Robert A Olie, Caroline Feys, Nathalie Allietta, Evangelos Terpos
This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m(2) intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation)...
April 6, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28379801/transplantation-for-myeloma-now-or-later
#10
Charles A Schiffer, Jeffrey A Zonder
No abstract text is available yet for this article.
April 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28379796/lenalidomide-bortezomib-and-dexamethasone-with-transplantation-for-myeloma
#11
Michel Attal, Valerie Lauwers-Cances, Cyrille Hulin, Xavier Leleu, Denis Caillot, Martine Escoffre, Bertrand Arnulf, Margaret Macro, Karim Belhadj, Laurent Garderet, Murielle Roussel, Catherine Payen, Claire Mathiot, Jean P Fermand, Nathalie Meuleman, Sandrine Rollet, Michelle E Maglio, Andrea A Zeytoonjian, Edie A Weller, Nikhil Munshi, Kenneth C Anderson, Paul G Richardson, Thierry Facon, Hervé Avet-Loiseau, Jean-Luc Harousseau, Philippe Moreau
Background High-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation. Methods We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients)...
April 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28376736/the-importance-of-censoring-in-competing-risks-analysis-of-the-subdistribution-hazard
#12
Mark W Donoghoe, Val Gebski
BACKGROUND: The analysis of time-to-event data can be complicated by competing risks, which are events that alter the probability of, or completely preclude the occurrence of an event of interest. This is distinct from censoring, which merely prevents us from observing the time at which the event of interest occurs. However, the censoring distribution plays a vital role in the proportional subdistribution hazards model, a commonly used method for regression analysis of time-to-event data in the presence of competing risks...
April 4, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28373701/benefit-of-continuous-treatment-for-responders-with-newly-diagnosed-multiple-myeloma-in-the-randomized-first-trial
#13
N J Bahlis, A Corso, L-O Mugge, Z-X Shen, P Desjardins, A-M Stoppax, O Decaux, T de Revel, M Granell, G Marit, H Nahi, H Demuynck, S-Y Huang, S Basu, T H Guthrie, A Ervin-Haynes, J Marek, G Chen, T Facon
The phase 3, randomized FIRST trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone, and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response...
April 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28371460/hematopoietic-stem-cell-transplantation-and-cellular-therapy
#14
REVIEW
H-J Kolb
Allogeneic stem cell transplantation is a form of immunotherapy that has increased the chances of survival for patients with relapsed leukemia and high risk leukemia in remission. The major obstacles are graft-vs-host disease (GVHD) involving vital organs and infections. A most efficacious prophylaxis of GVHD is by depleting of T cells from the graft. However, problems of T-depleted transplants are rejection, slow recovery of the immune system and high incidence of relapse of leukemia and myeloma. The major problem of allogeneic transplantation is the separation of a graft-vs-leukemia (GVL) effect from GVHD...
May 2017: HLA
https://www.readbyqxmd.com/read/28370630/long-term-follow-up-of-patients-with-multiple-myeloma-treated-with-total-body-irradiation-melphalan-conditioning
#15
Reinhold Munker, Ali Baghian, Yordanka Koleva, Patricia Andrews, Gunita S Matharoo, Ato E Wright, Nakhle Saba, Roy Weiner, Hanah Safah
BACKGROUND AND OBJECTIVES: Since a study published in 2002 showed a survival advantage of melphalan-only conditioning for stem cell transplantation (HSCT) over melphalan-total body irradiation (mel-TBI) in patients with multiple myeloma (MM), most centers abandoned mel-TBI. Mel-TBI causes more early toxicity and is more complicated to administer, but we speculated it may result in longer term survival with radiation as an independent treatment modality. Therefore, we analyzed the long-term outcome of patients with MM who received mel-TBI as part of conditioning at our center...
March 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28370486/clinical-presentation-and-outcomes-of-patients-with-type-1-monoclonal-cryoglobulinemia
#16
Surbhi Sidana, S Vincent Rajkumar, Angela Dispenzieri, Martha Q Lacy, Morie A Gertz, Francis K Buadi, Suzanne R Hayman, David Dingli, Prashant Kapoor, Wilson I Gonsalves, Ronald S Go, Yi Lisa Hwa, Nelson Leung, Amie L Fonder, Miriam A Hobbs, Steven R Zeldenrust, Stephen J Russell, John A Lust, Robert A Kyle, Shaji K Kumar
We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n=43, 42%) and ulcers/gangrene (n=35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n=24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients...
March 29, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28370401/cyclophosphamide-based-stem-cell-mobilization-in-relapsed-multiple-myeloma-patients-a-subgroup-analysis-from-the-phase-iii-trial-relapse
#17
Marc-Andrea Baertsch, Jana Schlenzka, Katharina Lisenko, Julia Krzykalla, Natalia Becker, Katja Weisel, Richard Noppeney, Hans Martin, Hans W Lindemann, Mathias Haenel, Axel Nogai, Christof Scheid, Hans Salwender, Roland Fenk, Ullrich Graeven, Peter Reimer, Martin Schmidt-Hieber, Martin Goerner, Ingo G H Schmidt-Wolf, Stefan Klein, Anthony D Ho, Hartmut Goldschmidt, Patrick Wuchter
OBJECTIVE: Analysis of the efficiency and toxicity of cyclophosphamide based stem cell mobilization in patients with relapsed mulitple myeloma (RMM). METHODS: Peripheral blood stem cells were mobilized with high dose cyclophosphamide (2 g /m(2) daily on days 1 and 2) and G-CSF plus pre-emptive/rescue plerixafor in RMM patients (1(st) to 3(rd) relapse) treated within the ReLApsE trial of the German-Speaking Myeloma Multicenter Group (GMMG). RESULTS: Mobilization was initiated with high dose cyclophosphamide and G-CSF in 30 patients...
March 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28368375/multiple-myeloma-patients-in-long-term-complete-response-after-autologous-stem-cell-transplantation-express-a-particular-immune-signature-with-potential-prognostic-implication
#18
A Arteche-López, A Kreutzman, A Alegre, P Sanz Martín, B Aguado, M González-Pardo, M Espiño, L M Villar, D García Belmonte, R de la Cámara, C Muñoz-Calleja
The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC)...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28368259/role-of-18-f-fdg-pet-ct-in-the-diagnosis-and-management-of-multiple-myeloma-and-other-plasma-cell-disorders-a-consensus-statement-by-the-international-myeloma-working-group
#19
REVIEW
Michele Cavo, Evangelos Terpos, Cristina Nanni, Philippe Moreau, Suzanne Lentzsch, Sonja Zweegman, Jens Hillengass, Monika Engelhardt, Saad Z Usmani, David H Vesole, Jesus San-Miguel, Shaji K Kumar, Paul G Richardson, Joseph R Mikhael, Fernando Leal da Costa, Meletios-Athanassios Dimopoulos, Chiara Zingaretti, Niels Abildgaard, Hartmut Goldschmidt, Robert Z Orlowski, Wee Joo Chng, Hermann Einsele, Sagar Lonial, Bart Barlogie, Kenneth C Anderson, S Vincent Rajkumar, Brian G M Durie, Elena Zamagni
The International Myeloma Working Group consensus aimed to provide recommendations for the optimal use of (18)fluorodeoxyglucose ((18)F-FDG) PET/CT in patients with multiple myeloma and other plasma cell disorders, including smouldering multiple myeloma and solitary plasmacytoma. (18)F-FDG PET/CT can be considered a valuable tool for the work-up of patients with both newly diagnosed and relapsed or refractory multiple myeloma because it assesses bone damage with relatively high sensitivity and specificity, and detects extramedullary sites of proliferating clonal plasma cells while providing important prognostic information...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28356669/c3-glomerulopathy-associated-to-multiple-myeloma-successfully-treated-by-autologous-stem-cell-transplant
#20
M A Hamzi, A Zniber, G E Badaoui, E Mahtat, Z Alhamany, R Bayahia, N Ouzeddoun
A 32-year-old male presented with advanced renal failure and nephrotic proteinuria due to lambda light chain multiple myeloma. Renal biopsy showed a proliferative glomerulonephritis with isolated C3 deposits. Renal recovery was obtained after chemotherapy and autologous stem cell transplant. We review previously described cases of C3 glomerulopathy associated with monoclonal gammopathy.
March 2017: Indian Journal of Nephrology
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