16 results on '"Gary J. Schiller"'
Search Results
2. Selinexor‐based regimens in patients with multiple myeloma after prior anti‐B‐cell maturation antigen treatment
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Muhamed Baljevic, Cristina Gasparetto, Gary J. Schiller, Sascha A. Tuchman, Natalie S. Callander, Suzanne Lentzsch, Jorge Monge, Rami Kotb, Nizar J. Bahlis, Darrell White, Christine I. Chen, Heather J. Sutherland, Sumit Madan, Richard LeBlanc, Michael Sebag, Christopher P. Venner, William I. Bensinger, Noa Biran, Andrew DeCastro, Dane R. Van Domelen, Chris Zhang, Jatin J. Shah, Sharon Shacham, Michael G. Kauffman, Ohad S. Bentur, and Brea Lipe
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anti‐BCMA ,multiple myeloma ,selinexor ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract There is a lack of consensus on therapy sequencing in previously treated multiple myeloma, particularly after anti‐B‐cell maturation antigen (BCMA) therapy. Earlier reports on selinexor (X) regimens demonstrated considerable efficacy in early treatment, and after anti‐BCMA‐targeted chimeric antigen receptor‐T cell therapy. Here, we present data from 11 heavily pretreated patients who predominantly received BCMA‐antibody‐drug conjugate therapy. We observe that X‐containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survival compared to patients’ prior anti‐BCMA therapies, despite being used later in the treatment course. In an area of evolving unmet need, these data reaffirm the efficacy of X‐based regimens following broader anti‐BCMA therapy.
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- 2022
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- View/download PDF
3. A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia
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Gregory A. Reed, Gary J. Schiller, Suman Kambhampati, Martin S. Tallman, Dan Douer, Mark D. Minden, Karen W. Yee, Vikas Gupta, Joseph Brandwein, Yulia Jitkova, Marcela Gronda, Rose Hurren, Aisha Shamas‐Din, Andre C. Schuh, and Aaron D. Schimmer
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Cox‐1 ,Cox‐4 ,mitochondrial protein synthesis ,pharmacodynamics ,pharmacokinetics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Acute myeloid leukemia (AML) cells meet the higher energy, metabolic, and signaling demands of the cell by increasing mitochondrial biogenesis and mitochondrial protein translation. Blocking mitochondrial protein synthesis through genetic and chemical approaches kills human AML cells at all stages of development in vitro and in vivo. Tigecycline is an antimicrobial that we found inhibits mitochondrial protein synthesis in AML cells. Therefore, we conducted a phase 1 dose‐escalation study of tigecycline administered intravenously daily 5 of 7 days for 2 weeks to patients with AML. A total of 27 adult patients with relapsed and refractory AML were enrolled in this study with 42 cycles being administered over seven dose levels (50–350 mg/day). Two patients experienced DLTs related to tigecycline at the 350 mg/day level resulting in a maximal tolerated dose of tigecycline of 300 mg as a once daily infusion. Pharmacokinetic experiments showed that tigecycline had a markedly shorter half‐life in these patients than reported for noncancer patients. No significant pharmacodynamic changes or clinical responses were observed. Thus, we have defined the safety of once daily tigecycline in patients with refractory AML. Future studies should focus on schedules of the drug that permit more sustained target inhibition.
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- 2016
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4. Selinexor‐based regimens in patients with multiple myeloma after prior anti‐B‐cell maturation antigen treatment
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Brea Lipe, Sascha A. Tuchman, Noa Biran, Michael Sebag, Jatin J. Shah, Sumit Madan, Michael Kauffman, Heather J. Sutherland, William I. Bensinger, Nizar J. Bahlis, Jorge Monge, Ohad S. Bentur, Rami Kotb, Cristina Gasparetto, Richard Leblanc, Muhamed Baljevic, Christopher P. Venner, Darrell White, Gary J. Schiller, Andrew DeCastro, Dane Van Domelen, Chris Zhiyi Zhang, Natalie S. Callander, Suzanne Lentzsch, Sharon Shacham, and Christine Chen
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business.industry ,B-Cell Maturation Antigen ,Immunology ,medicine ,Cancer research ,In patient ,Cell Biology ,Hematology ,medicine.disease ,business ,Biochemistry ,Multiple myeloma - Abstract
Background Multiple myeloma (MM) is considered an incurable hematologic malignancy despite a plethora of standard and novel agents. There is no consensus on the optimal sequencing of available therapies in relapsed/refractory MM (RRMM), even in the second line setting. Novel agents such as selinexor (XPOVIO [X]), an oral, first-in-class selective inhibitor of nuclear export (SINE) compound that blocks XPO1, or those that target B-cell maturation antigen (BCMA), have shown significant activity in RRMM. X is approved with bortezomib (V) and dexamethasone (XVd) in patients (pts) with at least 1 prior therapy and is not associated with known long-term clinically significant toxicities such as visual loss, cardiac dysfunction, renal failure, neuropathy, irreversible bone marrow suppression, second malignancies, venous thromboembolism, or rash. Currently, BCMA-targeting agents include 1 form each of chimeric antigen receptor T cell (CAR-T cell) and antibody drug conjugate (ADC) therapy approved in RRMM: idecabtagene vicleucel and belantamab mafodotin, respectively. BCMA-refractory MM represents an area of unmet need in MM without known standards for best treatment. Various novel combinations with X have demonstrated strong benefit in RRMM after 1 or more lines of therapy and activity even in CAR-T cell BCMA-refractory MM (N=7): 1 pt stringent complete (sCR), 3 very good partial (VGPR), 2 partial (PR), and 1 minimal (MR) response (Chari BJH 2020). Here we report on the outcomes of heavily pretreated RRMM pts, a majority of whom had received ADC-BCMA, and who were treated with X-containing regimens on the STOMP trial. Methods STOMP (NCT02343042) is a phase 1b/2, multi-arm, open-label trial of various combinations of X with backbone agents for pts with RRMM or newly diagnosed MM. Here we report on all pts in STOMP with prior anti-BCMA treatment who were treated on STOMP with X+pomalidomide +dexamethasone (XPd); XVd; X+carfilzomib+d (XKd); XPVd; and XPd+elotuzumab (E) (XPEd). Results In total, 11 pts with prior anti-BCMA therapy (6 pts with belantamab mafodotin; 1 each with MEDI2228, SEA-BCMA, BCMA BITE; 2 with idecabtagene vicleucel) were treated with 5 X-containing regimens (Table 1): 9 pts were treated with triplets XPd (4), XVd (3), or XKd (2) and 2 pts with quadruplets XPVd (1) or XPEd (1). Median age was 71 years (range 46-85), 7 pts (63.6%) were women, 11 pts were white. Median duration from MM diagnosis to treatment with a STOMP regimen was 6.9 years (range 2.3-12.8). Five pts (45.5%) had high-risk cytogenetics; pts received median of 6 prior therapies (range 4-10). Eight pts (72.7%) received anti-BCMA in their immediate prior line of therapy. Ten pts (90.9%) were previously treated with all backbone drugs of the STOMP treatments (i.e., X was the only new drug). The overall response rate (ORR) and clinical benefit rate (CBR) for the prior anti-BCMA-containing regimens were 40.0% (2 pts VGPR, 2 PR, 5 stable disease [SD], 1 progressive disease, 1 unknown). Median progression free survival (PFS) was 1.8 months (95% CI: 1.5, NE), and the 6-month PFS probability was 12.5% (95% CI: 2.1, 76.2). ORR for the X-based treatments was 54.5% and CBR was 81.8%: 1 pt VGPR, 5 PR, 3 MR, 2 SD. Median PFS was not reached (95% CI: 5.9, NE) and the 6-month PFS probability was 68.6% (95% CI: 40.3, 100.0). Median overall survival was 10.5 months (95% CI: 9.6, NE) and median time to discontinuation was 8.1 months (95% CI: 6.1, NE). The most common treatment-emergent adverse events were nausea and thrombocytopenia. Nausea was Grade (G) 1/2 (n=8, 72.7%); thrombocytopenia G1-4 in 8 pts (72.7%), 4 with ≥G3; there were no concurrent bleeding events. One pt on XPEd died of pulmonary nocardiosis considered to be associated with the 4-drug regimen. No new safety signals or long-term toxicities due to X were reported. Conclusions In this follow-up cohort of heavily pretreated pts, a majority of whom with MM refractory to ADC-BCMA, we demonstrate impressive potency and durability of the X-based treatments, particularly as compared to that of their prior anti-BCMA therapies. These data support the rationale for the development of novel regimens containing X plus immunomodulatory drugs or proteasome inhibitors in earlier lines of therapy, including first relapse, and further suggest their strong value in the emerging BCMA RRMM space. Figure 1 Figure 1. Disclosures Baljevic: Exelixis: Research Funding; Amgen: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen Research: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Gasparetto: Karyopharm: Consultancy, Honoraria, Speakers Bureau; Gsk: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; Sanofi: Consultancy, Honoraria, Speakers Bureau; Oncopeptide: Consultancy, Honoraria, Speakers Bureau. Schiller: Sangamo: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Celator: Research Funding; Geron: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; PrECOG: Research Funding; Onconova: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Genentech-Roche: Research Funding; Karyopharm: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; Abbvie: Research Funding; Forma: Research Funding; Deciphera: Research Funding; Daiichi-Sankyo: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Regimmune: Research Funding; FujiFilm: Research Funding; Gamida Cell Ltd.: Research Funding; Constellation Pharmaceuticals: Research Funding; Mateon: Research Funding; Astellas: Honoraria, Research Funding, Speakers Bureau; Arog: Research Funding; Delta-Fly: Research Funding; Tolero: Research Funding; Samus: Research Funding; Actuate: Research Funding; Actinium Pharmaceuticals, Inc: Research Funding; Trovagene: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Elevate: Research Funding; Bio: Research Funding; Ono-UK: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; Cyclacel: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Tuchman: Caelum: Consultancy, Research Funding; Sanofi / Genzyme: Consultancy, Research Funding; Shattuck Labs: Consultancy; Karyopharm: Research Funding; Oncopeptides: Consultancy. Lentzsch: Sanofi: Consultancy, Research Funding; Celularity: Consultancy; AbbVie: Consultancy; GSK: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Oncopeptides: Consultancy; Caelum Biosciences: Consultancy, Current holder of individual stocks in a privately-held company; Ossium Health: Consultancy; Magenta Therapeutics: Current equity holder in publicly-traded company; Kadmon: Current equity holder in publicly-traded company. Monge: Karyopharm: Research Funding; BMS: Consultancy. Kotb: Celgene: Honoraria; Karyopharm: Current holder of individual stocks in a privately-held company; Pfizer: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; BMS: Honoraria; Sanofi: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Akcea: Honoraria. Bahlis: GlaxoSmithKline: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Genentech: Consultancy. White: Forus: Consultancy, Honoraria; Antengene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Chen: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Sutherland: GSK: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; Karyopharm: Research Funding; Amgen: Consultancy. Madan: Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Sanofi: Consultancy, Research Funding; GSK: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Karyopharm: Research Funding, Speakers Bureau; Takeda: Speakers Bureau. Leblanc: Celgene/BMS: Research Funding; BMS/Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Canada: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Sanofi Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Sebag: Janssen: Research Funding; Amgen: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol Myers-Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Venner: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Research Funding; Amgen: Research Funding. Bensinger: BMS, Janssen, Poseida, Regeneron, Trillium: Research Funding; Amgen, BMS, Janssen, Sanofi: Speakers Bureau. DeCastro: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Van Domelen: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Bentur: Karyopharm Therapeutics: Current Employment, Current equity holder in publicly-traded company. Zhang: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Lipe: Seagen Inc.: Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; sanofi: Consultancy; GlaxoSmithKline: Consultancy; amgen: Research Funding; Cellectar: Research Funding; Karyopharm: Research Funding; Harpoon: Research Funding.
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- 2022
5. Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial
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Vu H. Duong, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Maria R. Baer, Wendy Stock, Tibor Kovacsovics, William Blum, Martha L. Arellano, Gary J. Schiller, Rebecca L. Olin, James M. Foran, Mark R. Litzow, Tara L. Lin, Prapti A. Patel, Matthew C. Foster, Robert L. Redner, Zeina Al‐Mansour, Christopher R. Cogle, Ronan T. Swords, Robert H. Collins, Jo‐Anne Vergilio, Nyla A. Heerema, Leonard Rosenberg, Ashley O. Yocum, Sonja Marcus, Timothy Chen, Franchesca Druggan, Mona Stefanos, Theophilus J. Gana, Abigail B. Shoben, Brian J. Druker, Amy Burd, John C. Byrd, Ross L. Levine, and Michael M. Boyiadzis
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Cancer Research ,Oncology - Published
- 2023
6. Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components
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Edward L. Snyder, Allison P. Wheeler, Majed Refaai, Claudia S. Cohn, Jessica Poisson, Magali Fontaine, Mary Sehl, Ajay K. Nooka, Lynne Uhl, Philip Spinella, Maly Fenelus, Darla Liles, Thomas Coyle, Joanne Becker, Michael Jeng, Eric A. Gehrie, Bryan R. Spencer, Pampee Young, Andrew Johnson, Jennifer J. O'Brien, Gary J. Schiller, John D. Roback, Elizabeth Malynn, Ronald Jackups, Scott T. Avecilla, Jin‐Sying Lin, Kathy Liu, Stanley Bentow, Ho‐Lan Peng, Jeanne Varrone, Richard J. Benjamin, and Laurence M. Corash
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Blood Platelets ,Respiratory Distress Syndrome ,Photosensitizing Agents ,pathogen reduction ,Clinical Sciences ,Immunology ,Transfusion Reaction ,Platelet Transfusion ,Hematology ,Cardiorespiratory Medicine and Haematology ,pulmonary adverse events ,Cohort Studies ,Rare Diseases ,Cardiovascular System & Hematology ,Clinical Research ,Respiratory ,Humans ,Immunology and Allergy ,Blood Transfusion ,Patient Safety ,assisted mechanical ventilation ,Lung ,Acute Respiratory Distress Syndrome - Abstract
BackgroundPlatelet transfusion carries risk of transfusion-transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion-related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion.Study designAn open label, sequential cohort study of transfusion-dependent hematology-oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment-emergent assisted mechanical ventilation (TEAMV) by non-inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri-transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality.ResultsBy modified intent-to-treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non-inferior to CPC for TEAMV (treatment difference -1.7%, 95% CI: (-3.3% to -0.1%); odds ratio=0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p= .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p= .151; odds ratio=0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p= .256); and allergic TR were significantly less with PRPC (p= .006). PC and RBC use were not increased with PRPC.DiscussionPRPC demonstrated reduced TEAMV with no excess treatment-related pulmonary morbidity.
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- 2022
7. Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma
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Brea Lipe, Kazuharu Kai, Muhamed Baljevic, Rami Kotb, Suzanne Lentzsch, Cristina Gasparetto, Chris Venner, Nizar J. Bahlis, Natalie S. Callander, Jatin P. Shah, Heather J. Sutherland, Noa Biran, Dane Van Domelen, Darrell White, Jean-Richard Saint-Martin, Gary J. Schiller, Michael Sebag, Sharon Shacham, Richard Leblanc, Adriana C Rossi, William I. Bensinger, Sascha A. Tuchman, Michael Kauffman, Heidi Sheehan, and Christine Chen
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Daratumumab ,In patient ,Refractory Multiple Myeloma ,business ,medicine.disease ,Dexamethasone ,Multiple myeloma ,medicine.drug - Abstract
We assessed the safety, efficacy, maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of selinexor, a first in class oral selective inhibitor of nuclear export (100 mg once weekly [QW] or 60 mg twice weekly), in combination with daratumumab (16 mg/kg per label) and dexamethasone (40 mg QW) (SDd) in patients with relapsed refractory multiple myeloma (RRMM). Thirty-four patients (median prior therapies, 3 [range, 2-10]) were enrolled; MM was refractory to proteasome inhibitor (PI) in 85%, immunomodulatory agent (IMiD) in 76%, both in 74%, and daratumumab in 6% of patients. Two dose-limiting toxicities (DLTs) were reported in the selinexor 60 mg twice-weekly cohort with no DLTs in the 100 mg QW cohort, making 100 mg QW the MTD and RP2D. Common treatment-related adverse events included thrombocytopenia (70.6%), nausea (70.6%), fatigue (61.8%), anemia (61.8%), and neutropenia (50.0%). Overall response rate was 73% and median progression-free survival 12.5 months in daratumumab-naïve patients. SDd was well tolerated and its promising efficacy suggests that further study of this PI- and IMiD-free regimen in RRMM patients who had at least one prior line of therapy including a PI and an IMiD but whose disease is naïve to daratumumab is warranted.
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- 2020
8. How to address second and therapy‐related acute myelogenous leukaemia
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Caspian Oliai and Gary J. Schiller
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Oncology ,medicine.medical_specialty ,Disease ,Immunotherapy, Adoptive ,Acute myelogenous leukaemia ,Disease-Free Survival ,World health ,Cell therapy ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Internal medicine ,Antibodies, Bispecific ,medicine ,Humans ,Therapy related ,business.industry ,Daunorubicin ,Remission Induction ,Age Factors ,Cytarabine ,Hematology ,Allografts ,Drug Resistance, Multiple ,Transplantation ,Leukemia, Myeloid, Acute ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Stem cell ,Augment ,business ,Stem Cell Transplantation ,030215 immunology - Abstract
Secondary acute myelogenous leukaemia (AML), as compared to de novo AML, occurs in the more elderly population, is independently more resistant to cytotoxic chemotherapy, has a higher relapse rate, and a worse prognosis. Secondary AML (sAML) is a heterogeneous disease, both biologically and clinically, even within the World Health Organization subgroups of sAML. Outcomes are the poorest in subgroups with sAML arising from an antecedent haematologic disorder which has been previously treated (ts-AML), and sAML in patients
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- 2019
9. Disease characteristics of diffuse large B‐cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience
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Daria Gaut, David Oveisi, Tahmineh Romero, Grant Howell, and Gary J. Schiller
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Transplantation, Autologous ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Autologous stem-cell transplantation ,Refractory ,Interquartile range ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Progression-free survival ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Lymphoma ,Survival Rate ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Recurrence, Local ,business ,Diffuse large B-cell lymphoma ,Follow-Up Studies ,030215 immunology - Abstract
While various tools such as the International Prognostic Index (IPI) and its derivatives exist for risk-stratification of diffuse large B-cell lymphoma (DLBCL) at diagnosis, patient and disease characteristics capable of predicting outcome after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) are not clearly defined. We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed and 33 refractory) who underwent HDC/ASCT at our institution from 2010-2015. After a median follow-up time of 4.6 years (interquartile range [IQR] 2.2-8.1), the likelihood of 5-year progression-free survival (PFS) was 62.2% (95% CI, 53.4%-72.4%) and the likelihood of 5-year overall survival (OS) was 68.9% (95% CI, 60.7%-78.2%). More than three chemotherapy regimens prior to ASCT was the only variable associated with lower likelihood of PFS (P = .004) and OS (P = 0.026). Male gender and high IPI score at time of ASCT were also associated with lower likelihood of PFS (P = .043; P = .013). NCCN IPI and age-adjusted IPI at time of ASCT were not predictive of outcome following ASCT. Patients with refractory and relapsed disease had similar outcomes post-ASCT (P = .207 for PFS, P = .073 for OS).
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- 2019
10. Pomalidomide plus low‐dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure
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William E. Pierceall, David S. Siegel, Kevin W. Song, Christy J. Samaras, Faiza Zafar, Amit Agarwal, Nizar J. Bahlis, Keith Stockerl-Goldstein, Giampaolo Talamo, Richy Agajanian, Jorge Mouro, Gary J. Schiller, Ehsan Malek, Shankar Srinivasan, Weiyuan Chung, Christopher S. Seet, Michael Sebag, and Hakan Kaya
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Male ,Oncology ,Cardiorespiratory Medicine and Haematology ,Dexamethasone ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Clinical endpoint ,Lenalidomide ,Multiple myeloma ,Cancer ,Aged, 80 and over ,education.field_of_study ,Bortezomib ,Hematology ,Middle Aged ,Thalidomide ,multiple myeloma ,Survival Rate ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,Research Paper ,medicine.drug ,Adult ,medicine.medical_specialty ,lenalidomide ,Clinical Trials and Supportive Activities ,Immunology ,Population ,dexamethasone ,pomalidomide ,Disease-Free Survival ,03 medical and health sciences ,Rare Diseases ,Refractory ,Clinical Research ,Internal medicine ,medicine ,Humans ,Haematological Malignancy‐Clinical ,education ,Aged ,business.industry ,Evaluation of treatments and therapeutic interventions ,Pomalidomide ,medicine.disease ,refractory ,business ,030215 immunology - Abstract
Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM-014 trial, we examined the safety and efficacy of pomalidomide plus low-dose dexamethasone immediately after lenalidomide-based treatment failure in patients with RRMM and two prior lines of therapy. Pomalidomide 4mg was given on days 1 to 21 of 28-day cycles. Dexamethasone 40mg (20mg for patients aged>75years) was given on days 1, 8, 15 and 22 of 28-day cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The intention-to-treat population comprised 56 patients; all received prior lenalidomide (87·5% lenalidomide refractory) and 39 (69·6%) received prior bortezomib. ORR was 32·1% (28·2% in the prior-bortezomib subgroup). Median PFS was 12·2months (7·9months in the prior-bortezomib subgroup). Median OS was 41·7months (38·6months in the prior-bortezomib subgroup). The most common grade 3/4 treatment-emergent adverse events were anaemia (25·0%), pneumonia (14·3%) and fatigue (14·3%). These findings support earlier sequencing of pomalidomide-based therapy in lenalidomide-pretreated patients with RRMM, including those who have become refractory to lenalidomide. Trial registration: www.ClinicalTrials.gov identifier NCT01946477.
- Published
- 2019
11. Author response for 'Disease Characteristics of Diffuse Large B‐Cell Lymphoma Predicting Relapse and Survival after Autologous Stem Cell Transplantation: A Single Institution Experience'
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David Oveisi, Tahmineh Romero, Daria Gaut, Grant Howell, and Gary J. Schiller
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Oncology ,medicine.medical_specialty ,Autologous stem-cell transplantation ,business.industry ,Internal medicine ,medicine ,Disease characteristics ,Single institution ,medicine.disease ,business ,Diffuse large B-cell lymphoma - Published
- 2019
12. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML
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David A. Rizzeri, Krzysztof Warzocha, Hagop M. Kantarjian, Donna E. Hogge, Stuart L. Goldberg, Gary J. Schiller, Jorge E. Cortes, Eric J. Feldman, Jonathan E. Kolitz, Arthur C. Louie, Arnaud Pigneux, Christian Recher, and Melissa L. Larson
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Anthracycline ,Daunorubicin ,business.industry ,Population ,Salvage therapy ,Cancer ,Phases of clinical research ,medicine.disease ,Surgery ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Cytarabine ,education ,business ,medicine.drug - Abstract
BACKGROUND CPX-351 is a liposome-encapsulated fixed-molar-ratio formulation of cytarabine and daunorubicin that exploits molar ratio–dependent drug-drug synergy to enhance antileukemic efficacy. METHODS This phase II study randomized 125 patients 2:1 to CPX-351 or investigators' choice of first salvage chemotherapy. Patients with acute myeloid leukemia (AML) in first relapse after initial Complete Remission (CR) lasting ≥1 month were stratified per the European Prognostic Index (EPI) into favorable, intermediate, and poor-risk groups based on duration of first CR, cytogenetics, age, and transplant history. Control salvage treatment was usually based on cytarabine and anthracycline, often with 1 or more additional agents. Survival at 1 year was the primary efficacy end point. RESULTS Patient characteristics were well balanced between the 2 study arms. Improvements in efficacy outcomes were observed following CPX-351, but did not meet prospectively defined statistical criteria for 1-year survival improvement in the overall population. Subset analyses of the EPI-defined poor-risk strata demonstrated higher response rates (39.3% vs 27.6%) and improvements in event-free survival (HR, 0.63; P = .08) and overall survival (HR, 0.55; P = .02). Also, 60-day mortality was lower in the CPX-351 study arm for poor-risk patients (16.1% vs 24.1%). CONCLUSIONS Taken together, the data suggest possible improved outcomes in CPX-351-treated first relapse AML patients with EPI-defined poor-risk disease. Cancer 2015;121:234–42. © 2014 American Cancer Society.
- Published
- 2014
13. Treatment of adults with acute lymphoblastic leukemia: Do the specifics of the regimen matter?
- Author
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Karen Seiter, David W. Golde, Katherine S. Panageas, Steven Coutre, Joseph O. Moore, Peter Maslak, Gary J. Schiller, Nicole Lamanna, Mark Weiss, Matt Kalaycio, and Leonard T. Heffner
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Vincristine ,Adolescent ,Disease-Free Survival ,law.invention ,Young Adult ,Maintenance therapy ,Randomized controlled trial ,law ,Internal medicine ,Acute lymphocytic leukemia ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Survival rate ,Aged ,Mitoxantrone ,business.industry ,Remission Induction ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Surgery ,Regimen ,Oncology ,Female ,business ,medicine.drug - Abstract
BACKGROUND: Induction therapy for adults with acute lymphoblastic leukemia (ALL) is similar across essentially all regimens, comprised of vincristine, corticosteroids, and anthracyclines intensified with cyclophosphamide, asparaginase, or both. Given the lack of randomized data, to date, no regimen has emerged as standard. The authors previously evaluated cytarabine 3 g/m2 daily for 5 days with mitoxantrone 80 mg/m2 (the ALL-2 regimen) as a novel induction regimen. Compared with historic controls, the ALL-2 regimen was superior in terms of incidence of complete remission, failure with resistant disease, and activity in patients with Philadelphia chromosome (Ph)-positive ALL. METHODS: The authors conducted a multicenter, prospective, randomized trial of the ALL-2 regimen compared with a standard 4-drug induction (the L-20 regimen). Patients also received consolidation, maintenance therapy, and central nervous system prophylaxis. The trial accrued patients from August 1996 to October 2004. RESULTS: The median follow-up for survivors was 7 years, and the median patient age was 43 years. Responses were evaluated in 164 patients. The treatment arms were balanced in terms of pretreatment characteristics. The frequency of complete remission for the ALL-2 regimen versus the L-20 regimen was 83% versus 71% (P = .06). More patients on the L-20 arm failed with resistant disease (21% vs 8%; P = .02). Induction deaths were comparable at 9% (ALL-2) versus 7% (L-20). The median survival was similar; and, at 5 years, the survival rate was 33% alive on the ALL-2 arm versus 27% on the L-20. CONCLUSIONS: Despite superior results of induction therapy with the ALL-2 regimen, this treatment did not improve long-term outcomes. When coupled to the reported experience of other studies in adults with ALL, the results of this randomized trial raise the possibility that ultimate outcomes in adult ALL may be independent of the specific regimen chosen. Cancer 2013. © 2012 American Cancer Society.
- Published
- 2012
14. Analysis of Multiple Myeloma Third Complementarity-Determining Regions Reveals Characteristics of Prenatal B Cells
- Author
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Robert Vescio, A. Kim, Alan Lichtenstein, James R. Berenson, Gary J. Schiller, C. H. Hong, L. A. Kunkel, and J. Cao
- Subjects
Adult ,Fetal Proteins ,Molecular Sequence Data ,B-Lymphocyte Subsets ,Immunoglobulin Variable Region ,Sequence alignment ,Computational biology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Text mining ,History and Philosophy of Science ,Sequence Homology, Nucleic Acid ,medicine ,Humans ,Base sequence ,Gene ,Multiple myeloma ,Base Sequence ,Genes, Immunoglobulin ,business.industry ,General Neuroscience ,medicine.disease ,Clone Cells ,biology.protein ,Nucleic acid ,Third Complementarity-Determining Regions ,Antibody ,Immunoglobulin Heavy Chains ,Multiple Myeloma ,business ,Sequence Alignment - Published
- 2008
15. Cladribine in the treatment of advanced relapsed or refractory low and intermediate grade non-Hodgkin's lymphoma
- Author
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Alexandra M. Levine, Byron M. Espina, Anil Tulpule, Myung Lee, Laura A. Harvey-Buchanan, Aziz U. Khan, Bharat N. Nathwani, William D. Boswell, and Gary J. Schiller
- Subjects
Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Neutropenia ,medicine.disease ,Gastroenterology ,Surgery ,Non-Hodgkin's lymphoma ,Lymphoma ,Fludarabine ,Oncology ,Refractory ,Internal medicine ,medicine ,Intermediate Grade ,Cladribine ,business ,medicine.drug - Abstract
BACKGROUND Cladribine (2-chlorodeoxyadenosine) is a purine nucleoside analog with cytotoxic activity against both resting and proliferating cells. Clinical studies with cladribine have reported antitumor activity against various hematologic malignancies. METHODS The authors studied responses to cladribine among patients with low and intermediate grade non-Hodgkin's lymphoma that had been refractory to or relapsed after prior chemotherapy. Cladribine was given intravenously over 2 hours at a dose of 0.14 mg/kg daily for 5 consecutive days, repeated every 4 weeks. RESULTS Twenty-eight patients (16 males, 12 females) with a median age of 58 years (range, 41-75 years) were accrued. Twenty-three patients had low grade and 5 had intermediate grade lymphoma. Stage IV disease was present in 22 (79%), and 17 (61%) had systemic B-symptoms. The majority (57%) had received 2 or more prior chemotherapy regimens (median, 2; range, 1-5); 6 had had prior fludarabine therapy. Major responses were documented in 32% (9 of 28 patients), with 4 complete remissions (CR) and 5 partial remissions (PR) after a median of 4 cycles (range, 1-9). One CR occurred in one patient with intermediate grade diffuse large cell lymphoma, and three of six patients who had had prior fludarabine therapy experienced CR or PR with cladribine. Severe hematologic toxicities included reversible neutropenia, protracted thrombocytopenia, and lymphopenia. Other reported adverse effects included mild-to-moderate fatigue, nausea, and diarrhea. CONCLUSIONS Cladribine is an active single agent in the treatment of patients with refractory or relapsed advanced stage indolent lymphoma, with major responses in one third of patients. Cancer 1998;83:2370-2376. © 1998 American Cancer Society.
- Published
- 1998
16. Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors
- Author
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Lynn Hunt, M. Wolin, Stephen A. Feig, James Gajewski, Stephen D. Nimer, Michael Lill, Mary C. Territo, Thomas R. Belin, Gary J. Schiller, and Richard E. Champlin
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Disease ,Human leukocyte antigen ,Transplantation, Autologous ,Gastroenterology ,Myelogenous ,Antigen ,Recurrence ,Risk Factors ,Unrelated Donor ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Child ,Bone Marrow Transplantation ,business.industry ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Survival Analysis ,Surgery ,Transplantation ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Child, Preschool ,Female ,Bone marrow ,business ,Chemoradiotherapy ,Follow-Up Studies - Abstract
Summary. Bone marrow transplantation from a histocompatible donor may produce complete remission in patients with induction failure or relapsed acute leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow from unrelated donors has become available for high-risk patients. In this study we analyse the results of matched unrelated bone marrow transplant in 55 patients with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28 patients with advanced acute lymphoblastic leukaemia and 27 patients with advanced acute myelogenous leukaemia, age 2–51, were treated withy high-dose chemoradiotherapy and transplantation of of 6/6 HLA matched (n= 46) or one antigen mismatched (n= 9) unrelated donor bone marrow. After a median follow-up of 36 months, 13 patients remain alive 17–24 months after transplant for a 2-year actuarial disease-free and overall survival of 23 ± 12% (median disease-free survival 3.5 months). The actuarial risk of relapse is 24 ± 16% at 1 year. Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients (57%). Significant prognostic factors for poor leukaemia-free survival include age >21, abnormal karyotype, and active leukaemia at the time of transplant. Other pretreatment characteristics such as gender or type of leukaemia were not significant prognostic factors. Our results show that matched unrelated bone marrow transplant for patients with advanced acute bone marrow transplant for patients with advanced acute leukaemia may provide long-term leukaemia-free survival, but transplant-related complications produce a sigbificant impact on survival with older age and adverse disease characteristics predicting for poor prognosis
- Published
- 1994
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