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relapsed multiple myeloma

Sumimasa Nagai, Keiya Ozawa
Background As relapsed disease is frequently the first target of newly developed therapies, it is vital to address the difficulty in demonstrating the efficacy of new drugs for relapsed malignancy in randomized phase 3 trials. Methods We analyzed the approved indications, target populations, and development status of post-marketing confirmatory trials of all oncology-related drugs that were granted accelerated approval for both hematological and solid malignancies. Furthermore, we searched for randomized phase 3 trials for adult patients with relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)...
February 17, 2018: Investigational New Drugs
Kristen B McCullough, Miriam A Hobbs, Jithma P Abeykoon, Prashant Kapoor
PURPOSE OF REVIEW: The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class...
February 15, 2018: Current Hematologic Malignancy Reports
Jie Ying, Miaomiao Zhang, Xiaoyan Qiu, Yu Lu
The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the potential to be effective treatment strategies for diseases. Among of all of the components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs are the largest family of ubiquitin E3 ligases and they play a critical role in substrate binding...
February 15, 2018: Cancer Chemotherapy and Pharmacology
Maria-Victoria Mateos, Hartmut Goldschmidt, Jesus San-Miguel, Joseph Mikhael, Lucy DeCosta, Lifen Zhou, Mihaela Obreja, Julie Blaedel, Zsolt Szabo, Xavier Leleu
We performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to investigate the efficacy of carfilzomib among subgroups of relapsed or refractory multiple myeloma patients who had early or late disease relapse following initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib, lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib and dexamethasone (Vd)...
February 15, 2018: Hematological Oncology
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
Elizabeth Dianne Pulte, Andrew Dmytrijuk, Lei Nie, Kirsten B Goldberg, Amy E McKee, Ann T Farrell, Richard Pazdur
On February 22, 2017, the U.S. Food and Drug Administration (FDA) granted approval for the use of lenalidomide as maintenance therapy after autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with multiple myeloma. The approval was based on evidence from two randomized, blinded trials of maintenance lenalidomide versus placebo in patients with myeloma who had undergone auto-HSCT along with a third trial of lenalidomide versus no therapy. Each of the trials demonstrated superior progression-free survival for the patients treated with lenalidomide...
February 7, 2018: Oncologist
Paul G Richardson, William I Bensinger, Carol Ann Huff, Caitlin L Costello, Nikoletta Lendvai, Jesus G Berdeja, Larry D Anderson, David S Siegel, Daniel Lebovic, Sundar Jagannath, Jacob P Laubach, Keith E Stockerl-Goldstein, Long Kwei, Fong Clow, Laurence Elias, Zeena Salman, Thorsten Graef, Elizabeth Bilotti, Ravi Vij
Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design...
February 13, 2018: British Journal of Haematology
Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Zabih Warraich, Sandra E Kurtin, Pavan Tenneti, Ali McBride, Faiz Anwer
We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...
February 1, 2018: Immunotherapy
Hang Quach, Simon Benson, Helen Haysom, Anne-Marie Wilkes, Nicole Zacher, Merrole Cole-Sinclair, Henry Miles Prince, Peter Mollee, Andrew Spencer, Phoebe Joy Ho, Simon J Harrison, Cindy Lee, Bradley Augustson, James Daly
In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen-Cilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs)...
February 2018: Internal Medicine Journal
Luciano J Costa, Heather J Landau, Saurabh Chhabra, Parameswaran Hari, Racquel Innis-Shelton, Kelly N Godby, Mehdi Hamadani, Roni Tamari, Kate Anderton, Pamela Dixon, Sergio A Giralt
We performed a phase 1/2 trial to investigate the safety and activity of the second generation proteasome inhibitor Carfilzomib (K) on days -3/-2 in combination with melphalan 200 mg/m2 (MEL200) on day -2 (K-MEL) in patients with relapsed multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (phases 1 and 2). Patients without progression received 12 cycles of K maintenance at 36 mg/m2 days 1,8,15 (schedule A) or days 1,2,15,16 (schedule B), with patients being treated for 2 cycles in each schedule and on the patient-preferred schedule for the remaining cycles (phase 2)...
February 1, 2018: Biology of Blood and Marrow Transplantation
Martin Köhler, Christine Greil, Michael Hudecek, Sagar Lonial, Noopur Raje, Ralph Wäsch, Monika Engelhardt
Multiple myeloma (MM) is the second most common hematologic malignancy and represents approximately 10% of all hematological neoplasms. Standard therapy consists of induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) or, if ASCT cannot be performed, standard doublet, triplet, or quadruplet, novel agent-containing induction treatment until progression. Although MM is still regarded as mostly incurable by current standards, the development of several novel compounds, combination therapies, and immunotherapy approaches has raised great hopes about transforming MM into an indolent, chronic disease and possibly achieving a cure for individual patients...
February 6, 2018: Cancer
Laurent Garderet, Simona Iacobelli, Linda Koster, Hartmut Goldschmidt, Jan-Erik Johansson, Jean Henri Bourhis, Marta Krejci, Xavier Leleu, Michael Potter, Didier Blaise, Christian Koenecke, Christian Peschel, Jakub Radocha, Bernd Metzner, Pascal Lenain, Kerstin Schäfer-Eckart, David Pohlreich, Mariella Grasso, Denis Caillot, Herman Einsele, Marco Ladetto, Stefan Schönland, Nicolaus Kröger
OBJECTIVES: To evaluate the outcome of a salvage third autologous stem cell transplantation (ASCT) in relapsed multiple myeloma. PATIENTS AND METHODS: We analyzed 570 patients who had received a third ASCT between 1997 and 2010 (EBMT data), of whom 482 patients had received tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients had an upfront ASCT with second and third transplants after subsequent relapses (ARARA group). RESULTS: With a median follow-up of 61 and 48 months after salvage third ASCT, the day 100 non-relapse mortality was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression free survival was 13 and 8 months and median overall survival (OS) was 33 and 15 months (AARA and ARARA groups, respectively)...
February 2, 2018: Biology of Blood and Marrow Transplantation
Wilson I Gonsalves, Ankit Kansagra
No abstract text is available yet for this article.
January 18, 2018: Acta Haematologica
Raphael E Steiner, Robert Z Orlowski, Hans C Lee
BACKGROUND: Acute pancreatitis is an uncommon complication of anti-myeloma agents. Ixazomib is a first-in-class oral proteasome inhibitor to receive regulatory approval for the treatment of multiple myeloma. This case report describes the first case of ixazomib-associated pancreatitis. CASE PRESENTATION: An 80-year-old female with relapsed multiple myeloma presented with severe diarrhea, nausea, vomiting, abdominal pain, and acute renal failure 3 weeks after starting ixazomib and dexamethasone for disease progression...
February 2, 2018: Acta Haematologica
Parameswaran Hari, Dorothy Romanus, Antonio Palumbo, Katarina Luptakova, Robert M Rifkin, Linh Mai Tran, Aditya Raju, Eileen Farrelly, Stephen J Noga, Marlo Blazer, Ajai Chari
BACKGROUND: In clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second-line therapy on overall survival. PATIENTS AND METHODS: Adults with NDMM from January 2008 to June 2015 were followed up to identify their second-line therapy...
January 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
Meletios Dimopoulos, Katja Weisel, Niels W C J van de Donk, Karthik Ramasamy, Barbara Gamberi, Matthew Streetly, Massimo Offidani, Frank Bridoux, Javier de la Rubia, Maria-Victoria Mateos, Antonio Ardizzoia, Elisabeth Kueenburg, Shona Collins, Antonia Di Micco, Barbara Rosettani, Yan Li, Pamela Bacon, Pieter Sonneveld
Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1...
February 2, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Pauline Gueneau, Marie-Lorraine Chretien, Amelie Cansac-Miet, Ludwig Aho, Ingrid Lafon, Camille Favennec, Julien Guy, Denis Caillot, Mathieu Boulin
OBJECTIVES: To investigate the efficacy, safety and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). METHODS: All patients (n=63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. RESULTS: Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance...
February 2, 2018: European Journal of Haematology
Dan T Vogl, David Dingli, Robert Frank Cornell, Carol Ann Huff, Sundar Jagannath, Divaya Bhutani, Jeffrey Zonder, Rachid Baz, Ajay Nooka, Joshua Richter, Craig Cole, Ravi Vij, Andrzej Jakubowiak, Rafat Abonour, Gary Schiller, Terri L Parker, Luciano J Costa, David Kaminetzky, James E Hoffman, Andrew J Yee, Ajai Chari, David Siegel, Rafael Fonseca, Scott Van Wier, Gregory Ahmann, Ilsel Lopez, Michael Kauffman, Sharon Shacham, Jean-Richard Saint-Martin, Carla D Picklesimer, Cassandra Choe-Juliak, A Keith Stewart
Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease)...
January 30, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yayoi Matsumura-Kimoto, Junya Kuroda, Hitomi Kaneko, Yuri Kamitsuji, Shin-Ichi Fuchida, Aya Nakaya, Hirohiko Shibayama, Nobuhiko Uoshima, Isao Yokota, Hitoji Uchiyama, Hideo Yagi, Satoru Kosugi, Toshimitsu Matsui, Jun Ishikawa, Mitsuhiro Matsuda, Kensuke Ohta, Masato Iida, Hirokazu Tanaka, Masayuki Kobayashi, Katsuya Wada, Chihiro Shimazaki, Shosaku Nomura, Kazunori Imada, Masayuki Hino, Itaru Matsumura, Yuzuru Kanakura, Akifumi Takaori-Kondo
Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached...
January 29, 2018: International Journal of Hematology
Jan Smetana, Jan Oppelt, Martin Štork, Luděk Pour, Petr Kuglík
Background: Catastrophic chromosomal event known as chromothripsis was proven to be a significant hallmark of poor prognosis in several cancer diseases. While this phenomenon is very rare in among multiple myeloma (MM) patients, its presence in karyotype is associated with very poor prognosis. Case presentation: In our case, we report a 62 year female patient with rapid progression of multiple myeloma (MM) into extramedullary disease and short overall survival (OS = 23 months)...
2018: Molecular Cytogenetics
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