642 results on '"DEXAMETHASONE"'
Search Results
2. Response rates to second‐line treatment with daratumumab bortezomib dexamethasone (DVD) in relapsed/refractory light chain amyloidosis (AL) after initial Bortezomib‐based regime.
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Bomsztyk, Joshua, Ravichandran, Sriram, Khwaja, Jahanzaib, Cohen, Oliver, Rauf, Muhammad U., Foard, Darren, Martinez‐Naharro, Ana, Venneri, Lucia, Whelan, Carol, Fontana, Marianna, Hawkins, Philip N., Gillmore, Julian, Lachmann, Helen, Mahmood, Shameem, and Wechalekar, Ashutosh D
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AMYLOIDOSIS , *BORTEZOMIB , *DARATUMUMAB , *DEXAMETHASONE , *SURVIVAL rate - Abstract
Summary: Bortezomib is regularly used as frontline therapy for systemic AL amyloidosis. We assess the efficacy of second‐line daratumumab‐bortezomib‐dexamethasone (DVD) in AL amyloidosis in bortezomib‐exposed patients. A total of 116 patients treated with second‐line DVD were identified from a prospective observational study of newly diagnosed AL amyloidosis (ALchemy). DVD was initiated in both the relapsed setting or where there was an inadequate response defined as very good partial response (VGPR) or VGPR with organ progression/lack of organ improvement. A complete response (CR)/VGPR to second‐line DVD was achieved in 81 (69.8%) patients. A CR/VGPR was achieved in 67 (79.7%) in those who achieved a VGPR/CR to first line versus 14/32 (43.8%) in those who did not. Where DVD was initiated due to an inadequate response to first line (vs. at relapse), the median event‐free survival (EFS) was 18 vs. 34 months (p = 0.002). If a CR/VGPR was achieved to DVD, the 2‐year EFS was still lower in those with prior inadequate response 54% vs. 66% (p = 0.062). DVD is an efficacious second‐line treatment in systemic AL amyloidosis in a bortezomib‐exposed population. However, the response to DVD is poorer in those with an inadequate response to first‐line bortezomib. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Inhibition of the Sec61 translocon overcomes cytokine‐induced glucocorticoid resistance in T‐cell acute lymphoblastic leukaemia
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Meyer, Lauren K, Delgado‐Martin, Cristina, Sharp, Phillip P, Huang, Benjamin J, McMinn, Dustin, Vincent, Tiffaney L, Ryan, Theresa, Horton, Terzah M, Wood, Brent L, Teachey, David T, Taunton, Jack, Kirk, Christopher J, and Hermiston, Michelle L
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2.1 Biological and endogenous factors ,Aetiology ,Cancer ,Cytokines ,Dexamethasone ,Glucocorticoids ,Humans ,Interleukin-7 ,Metabolism ,Inborn Errors ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Receptors ,Glucocorticoid ,SEC Translocation Channels ,T-Lymphocytes ,cytokine ,glucocorticoids ,Sec61 inhibitor ,T-cell acute lymphoblastic leukaemia ,Cardiorespiratory Medicine and Haematology ,Immunology - Abstract
Glucocorticoid (GC) resistance is a poor prognostic factor in T-cell acute lymphoblastic leukaemia (T-ALL). Interleukin-7 (IL-7) mediates GC resistance via GC-induced upregulation of IL-7 receptor (IL-7R) expression, leading to increased pro-survival signalling. IL-7R reaches the cell surface via the secretory pathway, so we hypothesized that inhibiting the translocation of IL-7R into the secretory pathway would overcome GC resistance. Sec61 is an endoplasmic reticulum (ER) channel that is required for insertion of polypeptides into the ER. Here, we demonstrate that KZR-445, a novel inhibitor of Sec61, potently attenuates the dexamethasone (DEX)-induced increase in cell surface IL-7R and overcomes IL-7-induced DEX resistance.
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- 2022
4. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B‐cell lymphoma
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Oluwole, Olalekan O, Bouabdallah, Krimo, Muñoz, Javier, De Guibert, Sophie, Vose, Julie M, Bartlett, Nancy L, Lin, Yi, Deol, Abhinav, McSweeney, Peter A, Goy, Andre H, Kersten, Marie José, Jacobson, Caron A, Farooq, Umar, Minnema, Monique C, Thieblemont, Catherine, Timmerman, John M, Stiff, Patrick, Avivi, Irit, Tzachanis, Dimitrios, Kim, Jenny J, Bashir, Zahid, McLeroy, Jeff, Zheng, Yan, Rossi, John M, Johnson, Lisa, Goyal, Lovely, and Meerten, Tom
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Lymphoma ,Rare Diseases ,Cancer ,Hematology ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adrenal Cortex Hormones ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Agents ,Immunological ,Biological Products ,Cytokine Release Syndrome ,Dexamethasone ,Female ,Humans ,Immunotherapy ,Adoptive ,Lymphoma ,Large B-Cell ,Diffuse ,Male ,Middle Aged ,large B-cell lymphoma ,axi-cel ,chimaeric antigen receptor-T cell ,prophylaxis ,corticosteroids ,cytokine release syndrome ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - Abstract
ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 106 CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.
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- 2021
5. Ixazomib in POEMS syndrome: 'Ixa'ctly what we need?
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Khouri, Jack
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PROTEASOME inhibitors , *CYCLOPHOSPHAMIDE , *POETRY (Literary form) , *DEXAMETHASONE , *SYNDROMES - Abstract
The role of the proteasome inhibitor ixazomib in the treatment of POEMS syndrome continues to evolve. He and colleagues present the results of a study investigating ixazomib in combination with cyclophosphamide and dexamethasone in newly diagnosed POEMS patients. The triplet showed excellent efficacy and tolerability, and constitutes an effective treatment option for patients with POEMS. Commentary on: He et al. An open‐label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly‐diagnosed POEMS syndrome. Br J Haematol 2024;205:478‐482. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Pomalidomide and dexamethasone until progression after first salvage therapy in multiple myeloma.
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Garderet, Laurent, Kuhnowski, Frederique, Berge, Benoit, Roussel, Murielle, Devlamynck, Laure, Petillon, Marie Odile, Escoffre‐Barbe, Martine, Lafon, Ingrid, Facon, Thierry, Leleu, Xavier, Karlin, Lionel, Perrot, Aurore, Stoppa, Anne‐Marie, Royer, Bruno, Chaleteix, Carine, Tiab, Mourad, Araujo, Carla, Lenain, Pascal, Macro, Margaret, and Belhadj, Karim
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SALVAGE therapy , *MULTIPLE myeloma , *DEXAMETHASONE , *PROGRESSION-free survival , *OVERALL survival , *LYMPHOPENIA - Abstract
Summary: Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013‐01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28‐day cycles of pomalidomide 4 mg daily on days 1–21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow‐up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression‐free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug‐related non‐haematological AEs (>5%) comprised 13% infections. Long‐term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L‐asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed NK/T‐cell lymphoma: A French retrospective study.
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Chaubard, Sammara, Marouf, Amira, Lavergne, David, Lemonnier, François, Rossignol, Julien, Clavert, Aline, Gressin, Rémy, Cartron, Guillaume, Waultier‐Rascalou, Agathe, Vargaftig, Jacques, Salles, Gilles, Bachy, Emmanuel, Ghesquières, Hervé, Tournilhac, Olivier, Chauchet, Adrien, Le Gouill, Steven, Damaj, Gandhi, Fornecker, Luc‐Matthieu, Sibon, David, and Obéric, Lucie
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METHOTREXATE , *LYMPHOMAS , *GEMCITABINE , *CANCER chemotherapy , *DEXAMETHASONE - Abstract
Summary: Extranodal NK/T‐cell lymphoma, nasal type is a rare and aggressive form of lymphoma, historically associated with poor prognosis. We report here the results of a retrospective multi‐centre study evaluating the efficacy of MGAD (methotrexate, gemcitabine, L‐asparaginase and dexamethasone) regimen (two cycles) combined with 'sandwich' radiotherapy in 35 patients with localised newly diagnosed extranodal NK/T‐cell lymphoma. Thirty‐two patients (91%) reached complete remission. With a long median follow‐up of 59.6 months, progression‐free and overall survival at 2 and 5 years were 71%, 80% and 53%, 73%, respectively. Around one third of the patients experienced relapse within a median time of 14.5 months. Side‐effects were manageable with grades 3–4 cytopenias, mucositis and infection in 50%, 24% and 21% of the cases, respectively. Monitoring of asparaginase activity was performed in 13 patients and showed inactivation of the drug in seven (54%) patients. Our results indicate that a short therapy by sandwich MGAD chemoradiotherapy is a tolerable and effective treatment option in localised newly diagnosed extranodal NK/T‐cell lymphoma patients. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Pomalidomide plus low‐dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure
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Siegel, David S, Schiller, Gary J, Song, Kevin W, Agajanian, Richy, Stockerl‐Goldstein, Keith, Kaya, Hakan, Sebag, Michael, Samaras, Christy, Malek, Ehsan, Talamo, Giampaolo, Seet, Christopher S, Mouro, Jorge, Pierceall, William E, Zafar, Faiza, Chung, Weiyuan, Srinivasan, Shankar, Agarwal, Amit, and Bahlis, Nizar J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Cancer ,Hematology ,Rare Diseases ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Dexamethasone ,Disease-Free Survival ,Female ,Humans ,Lenalidomide ,Male ,Middle Aged ,Multiple Myeloma ,Survival Rate ,Thalidomide ,pomalidomide ,dexamethasone ,lenalidomide ,multiple myeloma ,refractory ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - 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 4 mg was given on days 1 to 21 of 28-day cycles. Dexamethasone 40 mg (20 mg for patients aged >75 years) 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 12·2 months (7·9 months in the prior-bortezomib subgroup). Median OS was 41·7 months (38·6 months 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.
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- 2020
9. Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.
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Jakubowiak, Andrzej, Jasielec, Jagoda, Rosenbaum, Cara, Cole, Craig, Chari, Ajai, Mikhael, Joseph, Nam, Jennifer, McIver, Amanda, Severson, Erica, Stephens, Leonor, Tinari, Kathryn, Rosebeck, Shaun, Zimmerman, Todd, Hycner, Tyler, Turowski, Agata, Karrison, Theodore, and Zonder, Jeffrey
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carfilzomib ,dexamethasone ,relapsed/refractory multiple myeloma ,selinexor ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Cytogenetic Analysis ,Dexamethasone ,Drug Resistance ,Neoplasm ,Female ,Humans ,Hydrazines ,Male ,Middle Aged ,Multiple Myeloma ,Neoplasm Staging ,Oligopeptides ,Prognosis ,Recurrence ,Retreatment ,Treatment Outcome ,Triazoles - Abstract
Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation trial of twice-weekly selinexor in combination with carfilzomib and dexamethasone (SKd) to determine maximum tolerated dose in patients with RRMM (N = 21), with an expansion cohort to assess activity in carfilzomib-refractory disease and identify a recommended phase II dose (RP2D). During dose escalation, there was one dose-limiting toxicity (cardiac failure). The RP2D of twice-weekly SKd was selinexor 60 mg, carfilzomib 20/27 mg/m2 and dexamethasone 20 mg. The most common grade 3/4 treatment-emergent adverse events included thrombocytopenia (71%), anaemia (33%), lymphopenia (33%), neutropenia (33%) and infections (24%). Rates of ≥minimal response, ≥partial response and very good partial response were 71%, 48% and 14%, respectively; similar response outcomes were observed for dual-class refractory (PI and immunomodulatory drug)/quad-exposed (carfilzomib, bortezomib, lenalidomide and pomalidomide) patients (n = 17), and patients refractory to carfilzomib in last line of therapy (n = 13). Median progression-free survival was 3·7 months, and overall survival was 22·4 months in the overall population. SKd was tolerable and re-established disease control in RRMM patients, including carfilzomib-refractory patients. Registered at ClinicalTrials.gov (NCT02199665).
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- 2019
10. Should dexamethasone alone or in combination be the initial steroid for adult ITP: Still a relevant question.
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Skopec, Barbara and Bussel, James B.
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DEXAMETHASONE , *IDIOPATHIC thrombocytopenic purpura , *PLATELET count , *YOUNG women , *STEROIDS , *BLOOD platelet disorders - Abstract
Summary: Corticosteroids are used in first‐line treatment in newly diagnosed immune thrombocytopenia. The goal of treatment is primarily to decrease autoantibody‐mediated platelet clearance. Ideally initial treatment would not just increase the platelet count but also provide a long‐term sustained remission. While many clinicians use prednisone (PDN) as their first choice of corticosteroid, others prefer dexamethasone. The controversy is the subject of debates. Short courses of higher‐dose corticosteroids were first reported by the Andersen study in 1994. The study posited high‐dose dexamethasone as a 'cure' for all ITP patients. Later, studies addressed the number of dexamethasone cycles, indications to repeat cycles and timing between cycles, with varied long‐term results. The results with dexamethasone were compared to PDN in some studies: the four‐day cycles of dexamethasone work faster in increasing platelet counts and appear to reduce the occurrence of severe adverse events. Therefore, it is probably a better option for patients with low platelet counts and bleeding diathesis; however, curative superiority, the initial reason to administer it, compared to PDN is not well demonstrated. Across the studies, treatment with high‐dose dexamethasone seems to be safer, with lower incidence of all adverse events compared to PDN, which might be a reflection of shorter treatment duration and possibly also lower cumulative steroid dose. Dexamethasone in combination with rituximab in first‐line treatment produced higher response rates with better long‐term results compared to high‐dose dexamethasone alone and is a particularly good option in younger women. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Extended vincristine and dexamethasone pulse therapy may not be necessary for children with TCF3‐PBX1 positive acute lymphoblastic leukaemia.
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Wan, Yang, Zhang, Honghong, Zhang, Li, Cai, Jiaoyang, Yu, Jie, Hu, Shaoyan, Fang, Yongjun, Gao, Ju, Jiang, Hua, Yang, Minghua, Liang, Changda, Jin, Runming, Tian, Xin, Ju, Xiuli, Hu, Qun, Jiang, Hui, Li, Hui, Wang, Ningling, Sun, Lirong, and Leung, Alex W. K.
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LYMPHOBLASTIC leukemia , *ACUTE leukemia , *VINCRISTINE , *DEXAMETHASONE , *CHILD patients - Abstract
Summary: The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3‐PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non‐inferiority analysis of 263 newly diagnosed TCF3‐PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG‐ALL‐2015 clinical trial from January 2015 to December 2019 (ChiCTR‐IPR‐14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow‐up of 4.2 years, the 5‐year event‐free survival (EFS) and 5‐year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1–95.4) and 94.7% (95% CI, 90.9–98.6) comparable to those in the experimental group 89.2% (95% CI 84.1–94.7) and 95.6% (95% CI 91.8–99.6), respectively. Non‐inferiority was established as a one‐sided 95% upper confidence bound for the difference in probability of 5‐year EFS was 0.003, and that for 5‐year OS was 0.01 by as‐treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3‐PBX1 positive ALL. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma.
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Richardson, Paul, Hofmeister, Craig, Rosenbaum, Cara, Htut, Myo, Vesole, David, Berdeja, Jesus, Liedtke, Michaela, Chari, Ajai, Smith, Stephen, Lebovic, Daniel, Raje, Noopur, Byrne, Catriona, Liao, Eileen, Gupta, Neeraj, Bacco, Alessandra, Estevam, Jose, Berg, Deborah, and Baz, Rachid
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ixazomib ,multiple myeloma ,newly diagnosed ,oral ,twice-weekly ,Administration ,Oral ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Boron Compounds ,Dexamethasone ,Disease-Free Survival ,Dose-Response Relationship ,Drug ,Drug Administration Schedule ,Female ,Glycine ,Humans ,Lenalidomide ,Male ,Middle Aged ,Multiple Myeloma ,Treatment Outcome - Abstract
Weekly ixazomib with lenalidomide-dexamethasone (Rd) is feasible and has shown activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2 study (NCT01383928) evaluated the recommended phase 2 dose (RP2D), pharmacokinetics, safety and efficacy of twice-weekly ixazomib plus Rd in NDMM; 64 patients were enrolled across both phases. Patients received twice-weekly oral ixazomib 3·0 or 3·7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in cycles 9-16) for up to sixteen 21-day cycles, followed by maintenance with twice-weekly ixazomib alone. No dose-limiting toxicities were reported in cycle 1; the RP2D was 3·0 mg based on overall tolerability across multiple cycles. In 62 evaluable patients, the confirmed overall response rate was 94% (68% ≥very good partial response; 24% complete response). Median progression-free survival was 24·9 months. Responses (median duration 36·9 months for patients receiving the RP2D) deepened during treatment. Grade 3 drug-related adverse events (AEs) occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; hyperglycaemia, 8%. There were no grade 4 drug-related AEs. Thirteen patients discontinued due to AEs. Twice-weekly ixazomib-Rd offers substantial activity with promising long-term outcomes in NDMM patients but may be associated with greater toxicity compared with weekly ixazomib-Rd in this setting.
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- 2018
13. Lenalidomide, bortezomib and dexamethasone induction therapy for the treatment of newly diagnosed multiple myeloma: a practical review.
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McCaughan, Georgia J., Gandolfi, Sara, Moore, John J., and Richardson, Paul G.
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MULTIPLE myeloma , *LENALIDOMIDE , *BORTEZOMIB , *DEXAMETHASONE , *PROTEASOME inhibitors - Abstract
Summary: For patients with newly diagnosed multiple myeloma, survival outcomes continue to improve significantly: however, nearly all patients will relapse following induction treatment. Optimisation of induction therapy is essential to provide longer term disease control and the current standard of care for most patients incorporates an immunomodulatory agent and proteasome inhibitor, most commonly lenalidomide and bortezomib in combination with dexamethasone (RVD), with maintenance until progression. Historically there has been limited access to RVD as an induction strategy outside of the United States; fortunately, there is now increasing access worldwide. This review discusses the rationale for use of RVD as induction therapy and aims to provide guidance in prescribing this regimen in order to optimise efficacy while minimising the toxicities of treatment. We also highlight the increasing evidence for the utility of addition of a monoclonal antibody to the RVD backbone to deepen responses and potentially provide longer disease control. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Bendamustine in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: A phase II trial.
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Kumar, Sudhir, Sharma, Atul, Malik, Prabhat Singh, Gogia, Ajay, Pathak, Neha, Sahoo, Ranjit Kumar, Gupta, Ritu, Prasad, Chandra Prakash, and Kumar, Lalit
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MULTIPLE myeloma , *DEXAMETHASONE , *REFRACTORY materials , *PROGRESSION-free survival , *OVERALL survival - Abstract
Summary: Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m2day 1, pomalidomide 3 mg days 1–21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30–76) years and 15 (53.6%) were males. Patients had received a median (range) of three (two–six) prior lines and 85.7% were refractory to both lenalidomide and bortezomib. The primary end‐point was the overall response rate (ORR) defined as ≥partial response after at least three cycles. Secondary objectives were toxicity, progression‐free survival (PFS), time to progression and overall survival (OS). An intent‐to‐treat analysis was done. An ORR of 57.6% was achieved. Patients with extramedullary myeloma had a better response rate. At a median follow‐up of 8.6 months, the median PFS and OS were 6.2 and 9.7 months respectively. Toxicity was manageable; mainly haematological (neutropenia, 46.4%; anaemia, 42.8%; and thrombocytopenia, 7.1%). Bendamustine, pomalidomide and dexamethasone could be a novel combination for the heavily pretreated, lenalidomide‐refractory myeloma population. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Dexamethasone‐mediated inhibition of Notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells.
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Ahmed, Helal Mohammed Mohammed, Nimmagadda, Subbaiah Chary, Al‐Matary, Yahya S., Fiori, Maren, May, Tobias, Frank, Daria, Patnana, Pradeep Kumar, Récher, Christian, Schliemann, Christoph, Mikesch, Jan‐Henrik, Koenig, Thorsten, Rosenbauer, Frank, Hartmann, Wolfgang, Tuckermann, Jan, Dührsen, Ulrich, Lanying, Wei, Dugas, Martin, Opalka, Bertram, Lenz, Georg, and Khandanpour, Cyrus
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MESENCHYMAL stem cells , *STROMAL cells , *DEXAMETHASONE , *ACUTE myeloid leukemia , *LEUKEMIA - Abstract
Summary: Acute myeloid leukaemia (AML) is a haematological malignancy characterized by a poor prognosis. Bone marrow mesenchymal stromal cells (BM MSCs) support leukaemic cells in preventing chemotherapy‐induced apoptosis. This encouraged us to investigate leukaemia‐BM niche‐associated signalling and to identify signalling cascades supporting the interaction of leukaemic cells and BM MSC. Our study demonstrated functional differences between MSCs originating from leukaemic (AML MSCs) and healthy donors (HD MSCs). The direct interaction of leukaemic and AML MSCs was indispensable in influencing AML cell proliferation. We further identified an important role for Notch expression and its activation in AML MSCs contributing to the enhanced proliferation of AML cells. Supporting this observation, overexpression of the intracellular Notch domain (Notch ICN) in AML MSCs enhanced AML cells' proliferation. From a therapeutic point of view, dexamethasone treatment impeded Notch signalling in AML MSCs resulting in reduced AML cell proliferation. Concurrent with our data, Notch inhibitors had only a marginal effect on leukaemic cells alone but strongly influenced Notch signalling in AML MSCs and abrogated their cytoprotective function on AML cells. In vivo, dexamethasone treatment impeded Notch signalling in AML MSCs leading to a reduced number of AML MSCs and improved survival of leukaemic mice. In summary, targeting the interaction of leukaemic cells and AML MSCs using dexamethasone or Notch inhibitors might further improve treatment outcomes in AML patients. [ABSTRACT FROM AUTHOR]
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- 2022
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16. Patient‐reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study.
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Larocca, Alessandra, Leleu, Xavier, Touzeau, Cyrille, Bladé, Joan, Paner, Agne, Mateos, María‐Victoria, Cavo, Michele, Maisel, Christopher, Alegre, Adrían, Oriol, Albert, Raptis, Anastasios, Rodriguez‐Otero, Paula, Mazumder, Amitabha, Laubach, Jacob, Nadeem, Omar, Sandberg, Anna, Orre, Marie, Torrång, Anna, Bakker, Nicolaas A., and Richardson, Paul G.
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MULTIPLE myeloma , *PATIENT reported outcome measures , *PHYSICAL mobility , *QUALITY of life , *DEXAMETHASONE - Abstract
Summary: Relapsed/refractory multiple myeloma (RRMM) is known to have a high burden of disease and complications associated with refractoriness to prior lines of therapy. Severe pain and fatigue symptoms and impairments in physical and emotional functioning have been strongly linked to reduced health‐related quality of life (HRQoL) in patients with RRMM. Assessment of patient reported‐outcome measures from the pivotal, Phase II HORIZON study (OP‐106; NCT02963493) in patients with RRMM (n = 64) demonstrated that melphalan flufenamide (melflufen) plus dexamethasone treatment preserved HRQoL. Patients had clinically meaningful improvements, even after eight treatment cycles, in relevant scales such as global health status/QoL, physical functioning, emotional functioning, pain, and fatigue. Patients with triple‐class–refractory disease (n = 50) displayed similar improvements. Patient‐reported outcome deterioration was delayed for a substantial amount of time in patients who experienced a response to melflufen plus dexamethasone treatment relative to patients who did not experience a response. These findings support the notion that treatment with melflufen plus dexamethasone may sustain or improve HRQoL over time in patients with RRMM, including in patients with triple‐class–refractory disease for whom outcomes are generally worse. The clinical benefits observed in patients from the HORIZON trial are encouraging and supportive of translation into real‐world practice. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Reinduction therapy with everolimus in combination with dexamethasone, high‐dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD‐R3i)
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Gillessen, Sarah, Hüttmann, Andreas, Vucinic, Vladan, Müller, Horst, Plütschow, Annette, Viardot, Andreas, Topp, Max S., Kobe, Carsten, Böll, Boris, Eichenauer, Dennis A., Sasse, Stephanie, Haverkamp, Heinz, Schmitz, Christine, Borchmann, Sven, Bröckelmann, Paul J., Heger, Jan‐Michel, Fuchs, Michael, Engert, Andreas, Borchmann, Peter, and von Tresckow, Bastian
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HODGKIN'S disease , *EVEROLIMUS , *STEM cell transplantation , *DEXAMETHASONE , *COMPUTED tomography - Abstract
Summary: Reinduction chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second‐line standard of care for transplant‐eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high‐dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant‐eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase‐I‐part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end‐point of computed tomography (CT)‐based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT‐based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end‐point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy. [ABSTRACT FROM AUTHOR]
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- 2022
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18. A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16‐02 trial.
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Bergin, Krystal, Yuen, Flora, Wallington‐Beddoe, Craig, Kalff, Anna, Sirdesai, Shreerang, Reynolds, John, and Spencer, Andrew
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MULTIPLE myeloma , *OVERALL survival , *SURVIVAL rate , *THALIDOMIDE , *PROGRESSION-free survival - Abstract
Summary: We evaluated the efficacy and tolerability of continuous ixazomib‐thalidomide‐dexamethasone (ITd: 4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly). A total of 39 patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years with one to three prior lines of therapy were enrolled from two tertiary centres in Victoria and South Australia, Australia. The overall response rate (ORR) was 56·4% with a clinical benefit rate of 71·8%. The median progression‐free survival was 13·8 months [95% confidence interval (CI) 8·2–22·2] and median overall survival was not reached. The median time to best response and duration of response was 3·7 months (95% CI 2·8–10·5) and 18·4 months (95% CI 10·2–31·0) respectively. Prior immunomodulatory drug (IMID) exposure was associated with a lower ORR (40% vs. 73·7%, P = 0·03). Survival outcomes in patients with prior proteasome inhibitor (PI) and/or IMID exposure were similar. Patients received a median (range) of 11 (1–31) cycles of therapy and six patients (15%) remained on therapy at the time of final analysis. Grade 3/4 haematological and non‐haematological adverse events were reported in 7·7% and 20·6% of patients respectively. ITd dose reductions were required in 15·4%, 48·7% and 35·9% of patients respectively. The present study demonstrates promising effectiveness and tolerability of ITd as an affordable all‐oral PI‐IMID approach for RRMM. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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19. Safety and clinical activity of 5‐aza‐2′‐deoxycytidine (decitabine) with or without Hyper‐CVAD in relapsed/refractory acute lymphocytic leukaemia
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Benton, Christopher B, Thomas, Deborah A, Yang, Hui, Ravandi, Farhad, Rytting, Michael, O'Brien, Susan, Franklin, Anna R, Borthakur, Gautam, Dara, Samuel, Kwari, Monica, Pierce, Sherry R, Jabbour, Elias, Kantarjian, Hagop, and Garcia‐Manero, Guillermo
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Cancer ,Hematology ,Pediatric Cancer ,Rare Diseases ,Pediatric ,6.2 Cellular and gene therapies ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adolescent ,Adult ,Aged ,Antimetabolites ,Antineoplastic ,Antineoplastic Combined Chemotherapy Protocols ,Azacitidine ,Bone Marrow ,Chemical and Drug Induced Liver Injury ,Child ,Child ,Preschool ,Cyclophosphamide ,Cytarabine ,DNA Methylation ,DNA ,Neoplasm ,Decitabine ,Dexamethasone ,Doxorubicin ,Drug Administration Schedule ,Female ,Gastrointestinal Diseases ,Humans ,Hyperglycemia ,Infusions ,Intravenous ,Kaplan-Meier Estimate ,Male ,Methotrexate ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Recurrence ,Remission Induction ,Salvage Therapy ,Vincristine ,Young Adult ,DNA methylation ,clinical trial ,decitabine ,precursor cell lymphoblastic leukaemia-Lymphoma ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - Abstract
To test the safety and activity of 5-aza-2'-deoxycytidine (decitabine) in patients with relapsed/refractory acute lymphocytic leukaemia (ALL), we conducted a phase 1 study with two parts: administering decitabine alone or in combination with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine). Patients participated in either part of the study or in both parts sequentially. In the initial part, decitabine was administered intravenously at doses of 10-120 mg/m(2) per d for 5 d every other week in cycles of 28 d. In the combination part, patients were treated on the first 5 d of Hyper-CVAD with intravenous decitabine at 5-60 mg/m(2) per d. A total of 39 patients received treatment in the study: 14 in the first part only, 16 sequentially in both parts and 9 in the second part only. Decitabine was tolerated at all doses administered, and grade 3 or 4 toxic effects included non-life-threatening hepatotoxicity and hyperglycaemia. Induction of DNA hypomethylation was observed at doses of decitabine up to 80 mg/m(2) . Some patients who had previously progressed on Hyper-CVAD alone achieved a complete response when decitabine was added. Decitabine alone or given with Hyper-CVAD is safe and has clinical activity in patients with advanced ALL.
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- 2014
20. Evaluation of the pharmacokinetics of prednisolone in paediatric patients with acute lymphoblastic leukaemia treated according to Dutch Childhood Oncology Group protocols and its relation to treatment response.
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Sassen, Sebastiaan D. T., Mathôt, Ron A. A., Pieters, Rob, Haas, Valérie, Kaspers, Gertjan J. L., den Bos, Cor, Tissing, Wim J. E., Loo, D. Maroeska W. W., Bierings, Marc B., Sluis, Inge M., and Zwaan, C. Michel
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ACUTE leukemia , *LYMPHOBLASTIC leukemia , *CHILD patients , *PREDNISOLONE , *PHARMACOKINETICS - Abstract
Summary: Glucocorticoids form the backbone of paediatric acute lymphoblastic leukaemia (ALL) treatment. Many studies have been performed on steroid resistance; however, few studies have addressed the relationship between dose, concentration and clinical response. The aim of the present study was to evaluate the pharmacokinetics of prednisolone in the treatment of paediatric ALL and the correlation with clinical parameters. A total of 1028 bound and unbound prednisolone plasma concentrations were available from 124 children (aged 0–18 years) with newly diagnosed ALL enrolled in the Dutch Childhood Oncology Group studies. A population pharmacokinetic model was developed and post hoc area under the curve (AUC) was tested against treatment outcome parameters. The pharmacokinetics of unbound prednisolone in plasma was best described with allometric scaling and saturable binding to proteins. Plasma protein binding decreased with age. The AUC of unbound prednisolone was not associated with any of the disease parameters or treatment outcomes. Unbound prednisolone plasma concentrations correlated with age. No effect of exposure on clinical treatment outcome parameters was observed and does not substantiate individualised dosing. Poor responders, high‐risk and relapsed patients showed a trend towards lower exposure compared to good responders. However, the group of poor responders was small and requires further research. [ABSTRACT FROM AUTHOR]
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- 2021
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21. Health‐related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial.
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Plesner, Torben, Dimopoulos, Meletios A., Oriol, Albert, San‐Miguel, Jesus, Bahlis, Nizar J., Rabin, Neil, Suzuki, Kenshi, Yoon, Sung‐Soo, Ben‐Yehuda, Dina, Cook, Gordon, Goldschmidt, Hartmut, Grosicki, Sebastian, Qin, Xiang, Fastenau, John, Garvin, Wendy, Carson, Robin, Renaud, Thomas, and Gries, Katharine S.
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DARATUMUMAB , *MULTIPLE myeloma , *QUALITY of life , *DEXAMETHASONE , *PHYSICAL mobility , *LENALIDOMIDE - Abstract
Summary: In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D‐Rd) significantly improved progression‐free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient‐reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30‐item (EORTC QLQ‐C30) and the EuroQol 5‐dimensional descriptive system (EQ‐5D‐5L) questionnaires. Changes from baseline are presented as least‐squares mean changes with 95% confidence intervals (CIs) derived from a mixed‐effects model. PRO assessment compliance rates were high and similar in both D‐Rd and Rd groups through cycle 40 (week 156). In this on‐treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ‐C30 global health status, physical functioning, and pain scores in the D‐Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health‐related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D‐Rd treatment. These findings complement the sustained and significant improvement in progression‐free survival observed with D‐Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Pembrolizumab combined with carfilzomib and low‐dose dexamethasone for relapsed or refractory multiple myeloma: Cohort 2 of the phase I KEYNOTE‐023 study.
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Moreau, Philippe, Ghori, Razi, Farooqui, Mohammed, Marinello, Patricia, and San Miguel, Jesus
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MULTIPLE myeloma , *ACUTE kidney failure , *PEMBROLIZUMAB , *DEXAMETHASONE , *CARDIAC amyloidosis - Published
- 2021
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23. Melflufen plus dexamethasone in relapsed/refractory multiple myeloma: long‐term survival follow‐up from the Phase II study O‐12‐M1.
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Bringhen, Sara, Voorhees, Peter M., Plesner, Torben, Mellqvist, Ulf‐Henrik, Reeves, Brandi, Sonneveld, Pieter, Byrne, Catriona, Nordström, Eva, Harmenberg, Johan, Obermüller, Jakob, and Richardson, Paul G.
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MULTIPLE myeloma , *OVERALL survival , *DEXAMETHASONE , *SURVIVAL analysis (Biometry) - Abstract
Summary: An updated survival analysis was conducted for the Phase II study O‐12‐M1 of melphalan flufenamide (melflufen) plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) with two or more prior lines of therapy (including bortezomib and lenalidomide). Partial response or better was seen in 31%. After a 46‐month median overall survival (OS) follow‐up, melflufen plus dexamethasone had a median OS of 20·7 months (75th percentile OS, 47·5 months). The median time‐to‐next treatment for melflufen plus dexamethasone was 7·9 months. In summary, melflufen plus dexamethasone resulted in sustained long‐term clinical benefit in patients with RRMM. [ABSTRACT FROM AUTHOR]
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- 2021
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24. Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study.
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Camilleri, Marquita, Cuadrado, Maria, Phillips, Elizabeth, Wilson, William, Jenner, Richard, Pang, Gavin, Kamora, Sumaiya, Streetly, Matthew, Popat, Rakesh, Bygrave, Ceri, Owen, Roger, Cavenagh, James, Chapman, Mike, Sive, Jonathan, Eccersley, Lydia, Sheaff, Michael, Benjamin, Reuben, Ramasamy, Karthik, Cook, Gordon, and Virchis, Andres
- Subjects
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THROMBOTIC microangiopathies , *ACUTE kidney failure , *CYCLOPHOSPHAMIDE , *CARDAMOMS , *HYPERTENSIVE crisis , *DEXAMETHASONE , *HYPERTENSION - Abstract
Summary: Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) — a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end‐organ damage. To date, carfilzomib‐associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single‐agent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6/8 were hypertensive; 7/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomib‐associated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than five‐week treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib step‐up dosing (20 mg/m2 on day 1) at start of maintenance before dose escalation to 56 mg/m2 maximum, and adding 10 mg dexamethasone as premedication to maintenance carfilzomib infusions. No further TMA events occurred during maintenance following this amendment and the TMA incidence reduced from 4·2 to 1·6 per 1 000 patient cycles. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. Real‐world outcomes with bortezomib‐containing regimens and lenalidomide plus dexamethasone for the treatment of transplant‐ineligible multiple myeloma: a multi‐institutional report from the Canadian Myeloma Research Group database
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Jimenez‐Zepeda, Victor H., Venner, Christopher, McCurdy, Arleigh, Masih‐Khan, Esther, Atenafu, Eshetu G., Sebag, Michael, Stakiw, Julie, Song, Kevin, LeBlanc, Richard, Reiman, Tony, Louzada, Martha, Kotb, Rami, Gul, Engin, and Reece, Donna
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MULTIPLE myeloma , *RESEARCH teams , *DEXAMETHASONE , *PROGNOSIS , *PROGRESSION-free survival , *LENALIDOMIDE - Abstract
Summary: Bortezomib‐containing regimens (BCRs) represented standard, first‐line therapy for transplant‐ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low‐dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low‐dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression‐free survival (PFS) was 21·0, 21·1, 13·2 and 28·5 months (P = 0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7 months (P < 0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib‐steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician's choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real‐world outcomes in TIMM similar to those reported in clinical trials. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Health‐related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with bortezomib and dexamethasone: results from the phase III CASTOR trial.
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Hungria, Vania, Beksac, Meral, Weisel, Katja C., Nooka, Ajay K., Masszi, Tamas, Spicka, Ivan, Munder, Markus, Mateos, María‐Victoria, Mark, Tomer M., Qi, Ming, Qin, Xiang, Fastenau, John, Spencer, Andrew, Sonneveld, Pieter, Garvin, Wendy, Renaud, Thomas, and Gries, Katharine S.
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QUALITY of life , *MULTIPLE myeloma , *BORTEZOMIB , *DEXAMETHASONE - Abstract
Summary: In the phase III CASTOR trial, daratumumab, bortezomib and dexamethasone (D‐Vd) significantly extended progression‐free survival compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Here, we present patient‐reported outcomes (PROs) from the CASTOR trial. PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30‐item (EORTC QLQ‐C30) and the EuroQol 5‐dimensional descriptive system questionnaire. Treatment effects through Cycle 8 were measured by a repeated measures mixed‐effects model. After Cycle 8, PROs were only collected for patients in the D‐Vd group who continued on daratumumab monotherapy. Compliance rates for PRO assessments were high and similar between treatment groups. Mean changes from baseline were generally similar between treatment groups for EORTC QLQ‐C30 global health status (GHS), functioning and symptoms, and did not exceed 10 points for either treatment group. Subgroup analyses were consistent with the results observed in the overall population. There was no change in patients' health‐related quality of life for the first eight cycles of therapy; thereafter, patients treated with daratumumab over the long‐term reported improvements in GHS and pain. These results complement the significant clinical benefits observed with D‐Vd in patients with RRMM and support its use in this patient population. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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27. Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1‐acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group.
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Ocio, Enrique M., Motlló, Cristina, Rodríguez‐Otero, Paula, Martínez‐López, Joaquín, Cejalvo, Mª José, Martín‐Sánchez, Jesús, Bladé, Joan, García‐Malo, Mª Dolores, Dourdil, Mª Victoria, García‐Mateo, Aránzazu, Arriba, Felipe, García‐Sanz, Ramón, Rubia, Javier, Oriol, Albert, Lahuerta, Juan‐José, San‐Miguel, Jesús F., and Mateos, María‐Victoria
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DRUG efficacy , *PATIENT safety , *CLINICAL trials , *DEXAMETHASONE , *MULTIPLE myeloma - Abstract
Summary: This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty‐seven RRMM patients with a median of three prior lines (2–8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1·25 mg/m2 of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1–21 and dexamethasone 40 mg weekly. The defined threshold for success was achieved, with 18 out of 31 patients obtaining at least minor response (MR) in the phase II. In the global population, 51% of patients achieved at least partial response (PR) and 60% ≥MR, resulting in a median progression‐free survival (mPFS) of seven months and overall survival (OS) of 19 months. The main toxicity was haematological. Importantly, patients with low serum levels of alpha 1‐acid glycoprotein (AAG) at baseline (<800 mg/l) had a superior response (overall response rate of 62% vs. 17%; P = 0·04), which also translated into a longer mPFS (9 vs. 2 months; P = 0·014). In summary, filanesib with pomalidomide and dexamethasone is active in RRMM although with significant haematological toxicity. Most importantly, high levels of AAG can identify patients unlikely to respond to this strategy. Trial registration:clinicaltrials.gov identifier: NCT02384083. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. A real‐world study of panobinostat, weekly bortezomib and dexamethasone in a very heavily pretreated population of multiple‐myeloma patients.
- Author
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Bird, Sarah, Pawlyn, Charlotte, Nallamilli, Susanna, Sriskandarajah, Priya, Kaiser, Martin, Yong, Kwee, Popat, Rakesh, Rabin, Neil, and Boyd, Kevin
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MULTIPLE myeloma , *BORTEZOMIB , *DEXAMETHASONE - Abstract
The treatment of relapsed multiple myeloma (MM) is challenging due to increasing disease refractoriness, declining patient performance status and increasing patient co-morbidity.1 The combination of panobinostat, bortezomib and dexamethasone (PAN-Vd) is approved for the treatment of patients with relapsed MM based on the PANORAMA1 trial which compared PAN-Vd to placebo-Vd in patients with relapsed MM who were not previously refractory to bortezomib.2,3 Subgroup analysis showed that the benefit from PAN-Vd was greatest in patients who had received >=2 prior regimens including bortezomib and an immunomodulatory drug (IMiD) where the progression-free survival (PFS) was 12-5 months in the panobinostat arm I versus i 4-7 months in the placebo arm.3 The PANORAMA2 trial evaluated PAN-Vd in 55 heavily pretreated patients with bortezomib-refractory MM and the overall response rate (ORR) was 34-5% with a median PFS of 5-4 months.4 There is little published experience in such heavily pre-treated patients and in UK clinical practice this regimen is often positioned as 5th+ line therapy. Patients who were previously refractory to PI therapy had a significantly shorter PFS and OS than those not previously refractory (median PFS 1-5 months vs. 5-3 months, I P i = 0-008; OS 7-6 months vs. 12-6 months, I P i = 0-040; Fig 1G, H). Overall, our results are inferior to those of the PANORAMA1 study but our patient population is very different; when considering lines of therapy, PI-refractory status and cytopenias, it is likely that only 9% of our patients would have been eligible for PANORAMA1. [Extracted from the article]
- Published
- 2020
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29. Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis.
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Cohen, Oliver C., Sharpley, Faye, Gillmore, Julian D., Lachmann, Helen J., Sachchithanantham, Sajitha, Mahmood, Shameem, Fontana, Marianna, Whelan, Carol J., Martinez‐Naharro, Ana, Kyriakou, Charalampia, Rabin, Neil, Popat, Rakesh, Yong, Kwee, Cheesman, Simon, Shah, Raakhee, Hawkins, Philip N., and Wechalekar, Ashutosh D.
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ARRHYTHMIA , *AMYLOIDOSIS , *DEXAMETHASONE - Abstract
Summary: With improving outcomes in amyloid light‐chain (AL) amyloidosis, there is a need to study novel agents in this setting. We report outcomes of 40 patients with relapsed AL amyloidosis treated with ixazomib + lenalidomide + dexamethasone (IRd). Haematological responses were assessed on an intention‐to‐treat basis at three months: complete response (CR) – 8 (20·5%), very good partial response (VGPR) – 8 (20·5%), partial response (PR) – 7 (17·9%) and no response (NR) – 16 (41·0%). One patient had missing data. Six patients subsequently improved response. Best responses were: CR – 10 (25·6%), VGPR – 8 (20·5%), PR – 7 (17·9%), NR – 14 (35·9%). Cardiac and renal organ responses occurred in 5·6% and 13·3% respectively. Median progession‐free survival (PFS) was 17·0 months (95% CI 7·3–20·7 months), improving to 28·8 months (95% CI 20·6–37·0 months) in those achieving CR/VGPR. Median overall survival was 29·1 months (95% CI 24–33 months). Serious adverse events were seen in 14 (35·0%) patients inclusive of 15 admissions due to: infection (6/15, 40·0%), fluid overload (5/15, 33·3%), cardiac arrhythmia (2/15, 13·3%), renal dysfunction (1/15, 6·6%) and anaemia (1/15, 6·6%). In summary, IRd is an oral treatment option with a manageable toxicity profile leading to deep responses in 47% of patients with relapsed AL amyloidosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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30. Carfilzomib, venetoclax and dexamethasone for relapsed/refractory multiple myeloma.
- Author
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Boccon‐Gibod, Clémentine, Talbot, Alexis, Le Bras, Fabien, Frenzel, Laurent, Royer, Bruno, Harel, Stephanie, Lombion, Naelle, Belhadj, Karim, Cuccuini, Wendy, and Arnulf, Bertrand
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MULTIPLE myeloma , *DEXAMETHASONE , *PLASMA cell diseases - Abstract
Encouragingly, a phase 1 clinical trial evaluating venetoclax with bortezomib and dexamethasone in RRMM patients resulted in a promising ORR of 67% that did not differ between t(11;14)-positive and negative patients (Moreau I et al. i , [8]). These results prompted us to evaluate KVenD in 14 heavily pretreated RRMM patients, including t(11;14)-negative patients, in three departments of haematology. Regarding efficacy, ORR on KVenD among all patients was 5/14 (35-7%), with all responding patients in VGPR or better (Fig). [Extracted from the article]
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- 2020
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31. Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse.
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Montefusco, Vittorio, Corso, Alessandro, Galli, Monica, Ardoino, Ilaria, Pezzatti, Sara, Carniti, Cristina, Patriarca, Francesca, Gherlinzoni, Filippo, Zambello, Renato, Sammassimo, Simona, Marcatti, Magda, Nozza, Andrea, Crippa, Claudia, Cafro, Anna Maria, Baldini, Luca, and Corradini, Paolo
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MULTIPLE myeloma , *BORTEZOMIB , *DEXAMETHASONE , *PROGRESSION-free survival , *ADVERSE health care events - Abstract
Summary: Bortezomib‐ and lenalidomide‐containing regimens are well‐established therapies in multiple myeloma (MM). However, despite their extensive use, head‐to‐head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed‐duration therapies. In this open‐label, phase III study, we randomized MM patients at first relapse to receive either nine cycles of bortezomib plus cyclophosphamide plus dexamethasone (VCD) or lenalidomide plus cyclophosphamide plus dexamethasone (RCD). The primary endpoint was achievement of a very good partial response (VGPR) or better at six weeks after nine treatment cycles. From March 2011 to February 2015, 155 patients were randomized. VGPR or better was achieved by 12 patients (15%) in the VCD arm and 14 patients (18%) in the RCD arm (P = 0·70). Median progression‐free survival (PFS) was 16·3 (95% CI: 12·1–22·4) with VCD and 18·6 months (95% CI: 14·7–25·5) with RCD, and the two‐year overall survival (OS) was 75% (95% CI: 66–86%) and 74% (95% CI: 64–85%) respectively. In subgroup analyses, no differences in PFS were observed in bortezomib‐ and lenalidomide‐naïve patients, nor in patients who received a bortezomib‐based regimen in first line. Adverse events were consistent with the well‐established safety profiles of both drugs. Bortezomib and lenalidomide treatments were equally effective in terms of depth of response, PFS, and OS in MM patients at first relapse. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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32. Prognostic utility of pre‐transplantation [18F] fluorodeoxyglucose positron emission tomography/computed tomography in patients with diffuse large B‐cell lymphoma who underwent rituximab, dexamethasone, high‐dose cytarabine, carboplatin salvage chemotherapy
- Author
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Mesguich, Charles, Roch, Alexandre, Hindié, Elif, Milpied, Noël, Bordenave, Laurence, Tlili, Ghoufrane, and Bouabdallah, Krimo
- Subjects
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POSITRON emission tomography computed tomography , *COMPUTED tomography , *DEXAMETHASONE , *LYMPHOMAS , *CANCER chemotherapy - Abstract
Summary: We analysed the outcomes of 62 patients with refractory/relapsed diffuse large B‐cell lymphoma (rrDLBCL) who had pre‐transplantation fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after R‐DHAC (rituximab, dexamethasone, high‐dose cytarabine, carboplatin) salvage chemotherapy, and were evaluated using Deauville criteria and total lesion glycolysis (TLG). A positive pre‐transplantation PET/CT with Deauville score of 5 was associated with shorter progression‐free survival (PFS) (P = 0·01), while a Deauville score of 4 was not predictive of outcome. Only pre‐transplant TLG was significantly associated with both PFS (P = 0·005) and overall survival (P = 0·03). TLG deserves to be further investigated in prospective studies. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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33. Daratumumab and dexamethasone is safe and effective for triple refractory myeloma patients: final results of the IFM 2014‐04 (Etoile du Nord) trial.
- Author
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Boyle, Eileen M., Leleu, Xavier, Petillon, Marie‐Odile, Karlin, Lionel, Doyen, Chantal, Demarquette, Hélène, Royer, Bruno, Macro, Margaret, Moreau, Philippe, Fostier, Karel, Marie‐Lorraine, Chretien, Zarnitsky, Charles, Perrot, Aurore, Herbaux, Charles, Poulain, Stephanie, Manier, Salomon, Beauvais, David, Walker, Brian A., Wardell, Christopher P., and Vincent, Laure
- Subjects
- *
TERMINATION of treatment , *DEXAMETHASONE , *PROGRESSION-free survival , *MULTIPLE myeloma - Abstract
Summary: Single agent daratumumab has shown clinical activity in relapsed, refractory multiple myeloma (RRMM). The Intergroupe Francophone du Myélome 2014‐04 trial was designed to further investigate daratumumab in combination with dexamethasone in triple RRMM patients. Patients received daratumumab infusions in combination with weekly dexamethasone until disease progression or unacceptable toxicity. Fifty‐seven patients were included in the trial and evaluable for response. The overall response rate and the clinical benefit rate were 33% (n = 19) and 48% (n = 27), respectively. Five (8·8%) patients achieved a very good partial response or better. The median time to response was 4 weeks. For responding patients, the median progression‐free survival was 6·6 months, compared to 3·7 months (3·0–5·5) for those with a minimal or stable disease. The median overall survival (OS) for all patients was 16·7 months (11·2–24·0). For responding patients, the median OS was 23·23 months, whereas that of patients with progressive disease was 2·97 months. The incidence of infusion‐related reactions was 37%; all cases were manageable and did not lead to dose reduction or permanent treatment discontinuation. These data demonstrate that treatment with daratumumab and dexamethasone results in a meaningful long‐term benefit with an acceptable safety profile for patients with triple RRMM. [ABSTRACT FROM AUTHOR]
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- 2019
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- View/download PDF
34. Extended vincristine and dexamethasone pulse therapy may not be necessary for children with <scp> TCF3‐PBX1 </scp> positive acute lymphoblastic leukaemia
- Author
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Yang Wan, Honghong Zhang, Li Zhang, Jiaoyang Cai, Jie Yu, Shaoyan Hu, Yongjun Fang, Ju Gao, Hua Jiang, Minghua Yang, Changda Liang, Runming Jin, Xin Tian, Xiuli Ju, Qun Hu, Hui Jiang, Hui Li, Ningling Wang, Lirong Sun, Alex W. K. Leung, Xuedong Wu, Junxia Wang, Chi‐kong Li, Jun Yang, Jingyan Tang, Shuhong Shen, Xiaowen Zhai, Ching‐Hon Pui, and Xiaofan Zhu
- Subjects
Oncogene Proteins, Fusion ,Vincristine ,Antineoplastic Combined Chemotherapy Protocols ,Pre-B-Cell Leukemia Transcription Factor 1 ,Basic Helix-Loop-Helix Transcription Factors ,Humans ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Child ,Dexamethasone - Abstract
The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3-PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non-inferiority analysis of 263 newly diagnosed TCF3-PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG-ALL-2015 clinical trial from January 2015 to December 2019 (ChiCTR-IPR-14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow-up of 4.2 years, the 5-year event-free survival (EFS) and 5-year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1-95.4) and 94.7% (95% CI, 90.9-98.6) comparable to those in the experimental group 89.2% (95% CI 84.1-94.7) and 95.6% (95% CI 91.8-99.6), respectively. Non-inferiority was established as a one-sided 95% upper confidence bound for the difference in probability of 5-year EFS was 0.003, and that for 5-year OS was 0.01 by as-treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3-PBX1 positive ALL.
- Published
- 2022
35. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the <scp>GRIFFIN</scp> study
- Author
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Douglas W. Sborov, Muhamed Baljevic, Brandi Reeves, Jacob Laubach, Yvonne A. Efebera, Cesar Rodriguez, Luciano J. Costa, Ajai Chari, Rebecca Silbermann, Sarah A. Holstein, Larry D. Anderson, Jonathan L. Kaufman, Nina Shah, Huiling Pei, Sharmila Patel, Annelore Cortoos, J. Blake Bartlett, Jessica Vermeulen, Thomas S. Lin, Peter M. Voorhees, and Paul G. Richardson
- Subjects
Bortezomib ,Aspirin ,Antineoplastic Combined Chemotherapy Protocols ,Hematopoietic Stem Cell Transplantation ,Humans ,Venous Thromboembolism ,Hematology ,Multiple Myeloma ,Lenalidomide ,Transplantation, Autologous ,Dexamethasone - Abstract
Patients with multiple myeloma are at increased risk of vascular thromboembolic events (VTEs). This post hoc analysis evaluated VTEs in the randomised phase 2 GRIFFIN study (ClinicalTrials.gov Identifier: NCT02874742) that investigated lenalidomide/bortezomib/dexamethasone (RVd) ± daratumumab (D). Patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation (ASCT) received D-RVd/RVd induction, high-dose therapy and ASCT, D-RVd/RVd consolidation and up to 2 years of lenalidomide maintenance therapy ± D. VTE prophylaxis was recommended (at least aspirin, ≥162 mg daily) in accordance with International Myeloma Working Group guidelines. In the safety population (D-RVd, n = 99; RVd, n = 102), VTEs occurred in 10.1% of D-RVd patients and 15.7% of RVd patients; grade 2-4 VTEs occurred in 9.1% and 14.7%, respectively. Median time to the first onset of VTE was longer for D-RVd versus RVd patients (305 days vs 119 days). Anti-thrombosis prophylaxis use was similar between arms (D-RVd, 84.8% vs RVd, 83.3%); among patients with VTEs, prophylaxis use at time of first VTE onset was 60.0% for D-RVd and 68.8% for RVd. In summary, the addition of daratumumab to RVd did not increase the incidence of VTEs, but the cumulative VTE incidence was relatively high in this cohort and anti-thrombotic prophylaxis use was suboptimal.
- Published
- 2022
36. Lenalidomide, bortezomib and dexamethasone induction therapy for the treatment of newly diagnosed multiple myeloma: a practical review
- Author
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Georgia J. McCaughan, Sara Gandolfi, John J. Moore, and Paul G. Richardson
- Subjects
Bortezomib ,Antineoplastic Combined Chemotherapy Protocols ,Antibodies, Monoclonal ,Humans ,Induction Chemotherapy ,Hematology ,Neoplasm Recurrence, Local ,Multiple Myeloma ,Lenalidomide ,Proteasome Inhibitors ,Dexamethasone ,United States - Abstract
For patients with newly diagnosed multiple myeloma, survival outcomes continue to improve significantly: however, nearly all patients will relapse following induction treatment. Optimisation of induction therapy is essential to provide longer term disease control and the current standard of care for most patients incorporates an immunomodulatory agent and proteasome inhibitor, most commonly lenalidomide and bortezomib in combination with dexamethasone (RVD), with maintenance until progression. Historically there has been limited access to RVD as an induction strategy outside of the United States; fortunately, there is now increasing access worldwide. This review discusses the rationale for use of RVD as induction therapy and aims to provide guidance in prescribing this regimen in order to optimise efficacy while minimising the toxicities of treatment. We also highlight the increasing evidence for the utility of addition of a monoclonal antibody to the RVD backbone to deepen responses and potentially provide longer disease control.
- Published
- 2022
37. Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the <scp>CANDOR</scp> study
- Author
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Ola Landgren, Katja Weisel, Laura Rosinol, Cyrille Touzeau, Mehmet Turgut, Roman Hajek, Peter Mollee, Jin Seok Kim, Natalie Shu, Xuguang Hu, Chuang Li, and Saad Z. Usmani
- Subjects
Adult ,Treatment Outcome ,Antineoplastic Combined Chemotherapy Protocols ,Cytogenetic Analysis ,Humans ,Hematology ,Multiple Myeloma ,Prognosis ,Dexamethasone - Abstract
CANDOR compared the safety/efficacy of carfilzomib with dexamethasone and daratumumab (KdD) to carfilzomib with dexamethasone (Kd) in adults with relapsed/refractory multiple myeloma (RRMM). This CANDOR subgroup analysis evaluated outcomes based on cytogenetic risk. Overall response rates (KdD vs. Kd) were 81% versus 56% in high-risk and 87% versus 79% in standard-risk groups. Median progression-free survival was 11.2 versus 7.4 months in high-risk (hazard ratio, 0.56 [95% CI, 0.34, 0.93]) and not reached versus 16.6 months in standard-risk groups (0.56 [95% CI, 0.39, 0.80]). These data support the efficacy of KdD in RRMM treatment, including in patients with high-risk cytogenetics.
- Published
- 2022
38. Bendamustine in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: A phase II trial
- Author
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Sudhir Kumar, Atul Sharma, Prabhat Singh Malik, Ajay Gogia, Neha Pathak, Ranjit Kumar Sahoo, Ritu Gupta, Chandra Prakash Prasad, and Lalit Kumar
- Subjects
Adult ,Male ,Antineoplastic Combined Chemotherapy Protocols ,Bendamustine Hydrochloride ,Humans ,Female ,Hematology ,Middle Aged ,Multiple Myeloma ,Lenalidomide ,Dexamethasone ,Aged ,Thalidomide - Abstract
Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m
- Published
- 2022
39. Rituximab-bortezomib-dexamethasone induce high response rates in iMCD in clinical practice.
- Author
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Yin X, Liu Y, Zhong C, Lv Y, Xu D, Zhu L, Jin J, Meng H, and You L
- Subjects
- Humans, Bortezomib, Rituximab adverse effects, Dexamethasone, Castleman Disease diagnosis
- Abstract
Treatment options for idiopathic multicentric Castleman disease (iMCD) are currently limited, especially for patients who do not respond or are resistant to interleukin-6 inhibitors. For the first time, we innovatively designed a protocol using rituximab-bortezomib-dexamethasone (RVD) as first-line consolidation therapy in patients newly diagnosed with iMCD. Furthermore, we adopted a no-maintenance treatment strategy to simplify post-remission care. Five patients with iMCD were enrolled (including one with TAFRO syndrome) and underwent the RVD regimen, all of whom achieved partial response (PR) or better. After four cycles of RVD, three (60%) patients achieved PR, while one (20%) achieved a complete response. These five patients, who achieved PR or better, discontinued treatment but remained stable for a median follow-up of 11 months, with a duration of response of 7, 7, 10, 12 and 13 months, respectively. None of the patients experienced grade ≥3 adverse events during the observation period. Collectively, these findings demonstrated that the RVD regimen may be a promising treatment option for patients with iMCD. It was a safe and effective approach that resulted in lasting responses without the need for ongoing maintenance therapy., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
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40. Pembrolizumab combined with lenalidomide and low‐dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE‐023 study.
- Author
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Mateos, Maria‐Victoria, Orlowski, Robert Z., Ocio, Enrique M., Rodríguez‐Otero, Paula, Reece, Donna, Moreau, Philippe, Munshi, Nikhil, Avigan, David E., Siegel, David S., Ghori, Razi, Farooqui, Mohammed Z. H., Marinello, Patricia, and San-Miguel, Jesus
- Subjects
- *
MULTIPLE myeloma , *PEMBROLIZUMAB , *DEXAMETHASONE , *MESENCHYMAL stem cells - Abstract
Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study Keywords: pembrolizumab; relapsed/refractory; multiple myeloma; lenalidomide; dexamethasone In pre-clinical studies, lenalidomide, an immunomodulatory drug (IMiD), plus PD-1/PD-L1 (CD274) blockade enhanced MM cell death induced by PD-1/PD-L1 immune checkpoint blockade alone (Gorgun I et al i , [5]). Therefore, PD-1/PD-L1 inhibitor combination therapy for the treatment of MM could still be a therapeutic option. [Extracted from the article]
- Published
- 2019
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- View/download PDF
41. Enduring efficacy and tolerability of daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (GEN503): final results of an open‐label, phase 1/2 study.
- Author
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Plesner, Torben, Arkenau, Hendrik‐Tobias, Gay, Francesca, Minnema, Monique C., Boccadoro, Mario, Moreau, Philippe, Cavenagh, Jamie, Perrot, Aurore, Laubach, Jacob P., Krejcik, Jakub, Ahmadi, Tahamtan, Boer, Carla, Chen, Diana, Chiu, Christopher, Schecter, Jordan M., and Richardson, Paul G.
- Subjects
- *
MULTIPLE myeloma , *CLINICAL trial registries , *PLASMA cell diseases , *DEXAMETHASONE - Published
- 2019
- Full Text
- View/download PDF
42. Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study.
- Author
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Yimer, Habte, Ukropec, Jon, Qi, Ming, Rifkin, Robert M., Melear, Jason, Faber, Edward, Bensinger, William I., Burke, John M., Narang, Mohit, Stevens, Don, Gunawardena, Sriya, Lutska, Yana, Lin, Thomas S., and Qi, Keqin
- Subjects
- *
MULTIPLE myeloma , *BORTEZOMIB , *STEM cell transplantation , *DEXAMETHASONE , *PROGRESSION-free survival - Abstract
Summary: This United States community study evaluated the combination of daratumumab, bortezomib, cyclophosphamide and dexamethasone (D‐VCd) in newly diagnosed multiple myeloma (NDMM) and relapsed multiple myeloma (RMM). Patients received 4–8 induction cycles of bortezomib 1·5 mg/m2, cyclophosphamide 300 mg/m2 and dexamethasone 40 mg weekly. Intravenous daratumumab 16 mg/kg was administered as approved except for a split‐first dose in Cycle 1. Eligible patients underwent autologous stem cell transplantation. All patients received ≤12 daratumumab maintenance doses monthly. Eighty‐six NDMM and 14 RMM patients received ≥1 treatment dose. In NDMM patients, very good partial response or better (≥VGPR) and overall response rates after 4 induction cycles were 44% (primary endpoint) and 79%, respectively, and 56% and 81% at end of induction. The 12‐month progression‐free survival (PFS) rate was 87%. Efficacy was also observed in RMM patients. Fatigue (59%) and neutropenia (13%) were the most frequent treatment‐emergent adverse event (TEAE) and grade 3/4 TEAE, respectively. Infusion reactions occurred in 54% of patients, primarily during the first dose, and were mild (2% grade 3). The first 2 daratumumab infusions were 4·5 and 3·8 h (median). Overall, D‐VCd was well tolerated, split‐first daratumumab dosing was feasible, the ≥VGPR rate after 4 cycles was 44% and the 1‐year PFS rate was 87%. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
43. Extended follow‐up and the feasibility of Panobinostat maintenance for patients with Relapsed Multiple Myeloma treated with Bortezomib, Thalidomide, Dexamethasone plus Panobinostat (MUK six open label, multi‐centre phase I/II Clinical Trial).
- Author
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Popat, Rakesh, Yong, Kwee, Brown, Sarah R., Flanagan, Louise, Hall, Andrew, Gregory, Walter, Kishore, Bhuvan, Streetly, Matthew, Oakervee, Heather, Cavenagh, Jamie, Cook, Gordon, and Low, Eric
- Subjects
- *
MULTIPLE myeloma , *THALIDOMIDE , *CLINICAL trials , *BORTEZOMIB , *DEXAMETHASONE - Abstract
The article focuses on the feasibility in the use of the inhibitor Panobinostat in patients with relapsed multiple myeloma (MM) alongside dexamethasone and bortezomib. It talks about the clinical trial for progression-free survival (PFS) in patients going through disease relapse. It tells about the need to improve the efficiency of the drugs Dexamethasone, Bortezomib and Thalidomide alongside the inhibitor.
- Published
- 2019
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- View/download PDF
44. Phase 2 study of all‐oral ixazomib, cyclophosphamide and low‐dose dexamethasone for relapsed/refractory multiple myeloma.
- Author
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Kumar, Shaji K., Grzasko, Norbert, Delimpasi, Sosana, Jedrzejczak, Wieslaw W., Grosicki, Sebastian, Kyrtsonis, Marie‐Christine, Spencer, Andrew, Gupta, Neeraj, Teng, Zhaoyang, Byrne, Catriona, Labotka, Richard, and Dimopoulos, Meletios A.
- Subjects
- *
MELPHALAN , *DEXAMETHASONE , *MULTIPLE myeloma , *RESPIRATORY infections , *PERIPHERAL neuropathy , *PROGRESSION-free survival - Abstract
Summary: There is a need for efficacious, convenient treatments with long‐term tolerability for patients with relapsed/refractory multiple myeloma (RRMM). This phase 2 study evaluated the all‐oral combination of ixazomib, cyclophosphamide and dexamethasone (ICd). Patients with RRMM received ixazomib 4 mg and cyclophosphamide 300 mg/m2 on days 1, 8 and 15, and dexamethasone 40 mg on days 1, 8, 15 and 22 in 28‐day cycles. The primary endpoint was overall response rate (ORR). Seventy‐eight patients were enrolled (median age 63·5 years). At data cut‐off, patients had received a median of 12 treatment cycles; 31% remained on treatment. ORR was 48% [16% very good partial response or better (≥VGPR)]. ORR was 64% and 32% in patients aged ≥65 and <65 years (25% and 16% ≥VGPR), respectively. At a median follow‐up of 15·2 months, median progression‐free survival (PFS) was 14·2 months, with a trend towards better PFS in patients aged ≥65 years vs. <65 years (median 18·7 months vs. 12·0 months; hazard ratio 0·62, P = 0·14). ICd was well tolerated. The most common treatment‐emergent adverse events were diarrhoea (33%), nausea (24%), upper respiratory tract infection (24%), and thrombocytopenia (22%); 10 patients (13%) had peripheral neuropathy (one grade 3). This study is registered at ClinicalTrials.gov (NCT02046070). [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
45. Inhibition of the Sec61 translocon overcomes cytokine‐induced glucocorticoid resistance in T‐cell acute lymphoblastic leukaemia
- Author
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Lauren K. Meyer, Cristina Delgado‐Martin, Phillip P. Sharp, Benjamin J. Huang, Dustin McMinn, Tiffaney L. Vincent, Theresa Ryan, Terzah M. Horton, Brent L. Wood, David T. Teachey, Jack Taunton, Christopher J. Kirk, and Michelle L. Hermiston
- Subjects
Receptors, Glucocorticoid ,Interleukin-7 ,T-Lymphocytes ,Cytokines ,Humans ,Hematology ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Glucocorticoids ,Dexamethasone ,Metabolism, Inborn Errors ,SEC Translocation Channels - Abstract
Glucocorticoid (GC) resistance is a poor prognostic factor in T-cell acute lymphoblastic leukaemia (T-ALL). Interleukin-7 (IL-7) mediates GC resistance via GC-induced upregulation of IL-7 receptor (IL-7R) expression, leading to increased pro-survival signalling. IL-7R reaches the cell surface via the secretory pathway, so we hypothesized that inhibiting the translocation of IL-7R into the secretory pathway would overcome GC resistance. Sec61 is an endoplasmic reticulum (ER) channel that is required for insertion of polypeptides into the ER. Here, we demonstrate that KZR-445, a novel inhibitor of Sec61, potently attenuates the dexamethasone (DEX)-induced increase in cell surface IL-7R and overcomes IL-7-induced DEX resistance.
- Published
- 2022
46. A retrospective study of R‐DHAP/Ox for early progressing follicular lymphoma.
- Author
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Ghione, Paola, Cavallo, Federica, Visco, Carlo, Chen, Zhengming, Castellino, Alessia, Tisi, Maria C., Dogliotti, Irene, Nicolosi, Maura, Boccadoro, Mario, Leonard, John P., Vitolo, Umberto, and Martin, Peter
- Subjects
- *
LYMPHOMA treatment , *RITUXIMAB , *DEXAMETHASONE , *CYTARABINE , *CISPLATIN , *OXALIPLATIN , *KAPLAN-Meier estimator , *RETROSPECTIVE studies - Abstract
The article presents a retrospective study which examined the effectiveness of rituximab, dexamethasone, cytarabine, cisplatin/oxaliplatin (R-DHAP/Ox) as treatment for early progressing follicular lymphoma. Also cited are the effectiveness of R-DHAP/Ox against diffuse large B cell lymphoma (DLCBL) with germinal centre subtype, and the use of the Kaplan-Meier method in estimating the subjects' survival probability.
- Published
- 2018
- Full Text
- View/download PDF
47. Significance of anti‐HBc serological status in primary immune thrombocytopenia
- Author
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Chaoyang Li, Yafei Yu, Haoyi Wang, Lizhen Li, Lin Wang, Ruting Wang, Yu Hou, Lingjun Wang, Ming Hou, Miao Xu, Jun Peng, and Xiaofei Ni
- Subjects
Adult ,Male ,Hepatitis B virus ,HBsAg ,medicine.medical_specialty ,medicine.disease_cause ,Gastroenterology ,Serology ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Hepatitis B Antibodies ,Prospective cohort study ,Dexamethasone ,Retrospective Studies ,Purpura, Thrombocytopenic, Idiopathic ,business.industry ,Recombinant Human Thrombopoietin ,virus diseases ,Retrospective cohort study ,Hematology ,Middle Aged ,digestive system diseases ,Female ,Rituximab ,business ,medicine.drug - Abstract
The association of previous hepatitis B virus (HBV) exposure [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc/HBcAb) positive] with disease severity and decision on treatment option in primary immune thrombocytopenia (ITP) patients remains unclear. Data from 725 patients diagnosed with ITP were analyzed to elucidate the association between anti-HBc serological status and disease severity. Data from a published prospective study [high-dose dexamethasone (HD-DXM), HD-DXM plus recombinant human thrombopoietin, NCT01734044] and two retrospective studies (standard-dose and low-dose rituximab) were rearranged to evaluate the impact of anti-HBc serological status on the response and outcome to ITP-specific treatments and the risk of HBV reactivation related to these treatments. The prevalence of HBsAg- HBcAb+ and HBsAg- HBcAb- in ITP patients was 51·03% and 48·97% respectively. Compared to the HBsAg- HBcAb- group, patients in the HBsAg- HBcAb+ group had lower platelet count, higher bleeding score, and longer hospitalization (P = 0·002, 0·033, and 0·008 respectively). Moreover, the initial complete response rate of HBsAg- HBcAb+ patients was lower than that of HBsAg- HBcAb- patients (45·2% vs 59·8%, P = 0·027). In conclusion, previous HBV exposure was correlated with disease severity and hospitalization in ITP patients. Anti-HBc positivity may be considered as a predictor for poor response to ITP-specific treatments.
- Published
- 2021
48. Reinduction therapy with everolimus in combination with dexamethasone, high‐dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD‐R3i)
- Author
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Horst Müller, Heinz Haverkamp, Peter Borchmann, Andreas Viardot, Jan-Michel Heger, Christine Schmitz, Bastian von Tresckow, Michael Fuchs, Dennis A. Eichenauer, Vladan Vucinic, Andreas Engert, Stephanie Sasse, Max S. Topp, Paul J Bröckelmann, Annette Plütschow, Sarah Gillessen, Boris Böll, Sven Borchmann, Carsten Kobe, and Andreas Hüttmann
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Randomization ,medicine.medical_treatment ,Medizin ,Kaplan-Meier Estimate ,Dexamethasone ,Young Adult ,Refractory ,Recurrence ,Germany ,DHAP ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Everolimus ,Neoplasm Staging ,Chemotherapy ,business.industry ,Remission Induction ,Cytarabine ,Induction Chemotherapy ,Hematology ,Middle Aged ,Prognosis ,Hodgkin Disease ,Regimen ,Drug Resistance, Neoplasm ,Positron-Emission Tomography ,Retreatment ,Female ,Cisplatin ,Neoplasm Grading ,business ,medicine.drug - Abstract
Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.
- Published
- 2021
49. Comparison of venous thromboembolism incidence in newly diagnosed multiple myeloma patients receiving bortezomib, lenalidomide, dexamethasone (RVD) or carfilzomib, lenalidomide, dexamethasone (KRD) with aspirin or rivaroxaban thromboprophylaxis
- Author
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Malin Hultcrantz, Hani Hassoun, Sham Mailankody, Sydney Lu, Dhwani Patel, Tim J Peterson, Neha Korde, Carlyn Tan, Katrina M Piedra, Urvi A Shah, Alexander M. Lesokhin, Jennifer S. Orozco, Andriy Derkach, and Cy Wilkins
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Dexamethasone ,Article ,Bortezomib ,chemistry.chemical_compound ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lenalidomide ,Multiple myeloma ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Aspirin ,Rivaroxaban ,business.industry ,Incidence ,Disease Management ,Retrospective cohort study ,Venous Thromboembolism ,Hematology ,Middle Aged ,medicine.disease ,Carfilzomib ,chemistry ,Female ,Disease Susceptibility ,Neoplasm Grading ,Multiple Myeloma ,business ,Oligopeptides ,medicine.drug - Abstract
Incidence of venous thromboembolism (VTE) varies across different regimens in newly diagnosed multiple myeloma (NDMM) patients. Limited data exist on the use of direct oral anticoagulants as thromboprophylaxis in the setting of haematologic malignancies, specifically multiple myeloma. In this retrospective study of 305 NDMM patients, VTE rates in those treated with carfilzomib, lenalidomide, dexamethasone (KRD) + aspirin (ASA), bortezomib, lenalidomide, dexamethasone (RVD) + ASA, and KRD + rivaroxaban were statistically significant, 16·1%, 4·8%, and 4·8%, respectively. The findings confirm a higher incidence of VTE when using KRD induction compared to RVD induction and reveal that the use of low-dose rivaroxaban thromboprophylaxis can mitigate this risk without an observable increase in bleeding rates.
- Published
- 2021
50. Improved survival outcomes despite older age at diagnosis: an era‐by‐era analysis of patients with primary central nervous system lymphoma treated at a single referral centre in the United Kingdom
- Author
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Dorothee P. Auer, Rocio Figueroa, Mark Bishton, Christopher P. Fox, Vishakha Sovani, Nicolas Martinez-Calle, Eleanor James, Furqaan A Kaji, Paul Byrne, Eric M Bessell, Joanne Adlington, Stuart Smith, Matthew J. Grainge, Simon M. L. Paine, and M. O'Donoghue
- Subjects
Male ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Transplantation, Autologous ,Dexamethasone ,Drug Administration Schedule ,Central Nervous System Neoplasms ,Hospitals, University ,Autologous stem-cell transplantation ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Mortality ,Cyclophosphamide ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Hazard ratio ,Age Factors ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Primary central nervous system lymphoma ,Hematology ,Middle Aged ,medicine.disease ,Carmustine ,Progression-Free Survival ,United Kingdom ,Confidence interval ,Methotrexate ,Treatment Outcome ,Doxorubicin ,Vincristine ,Cohort ,Female ,Rituximab ,business ,medicine.drug - Abstract
Observational studies with long-term follow-up of patients with primary central nervous system lymphoma (PCNSL) are scarce. Patient data over a period of four decades were retrospectively analysed from databases at Not-tingham University Hospitals Trust, UK. The cohort was delineated by two distinct therapeutic eras; the first from 01/01/1982 to 31/12/2010 (n = 147) and the second 01/01/2011 to 31/07/2020 (n = 125). The median age at diagnosis was significantly older in the second era compared to the first (69 and 65 years respectively, P = 0·003). The 3-, 6-and 12-month overall survival (OS) rates in the second era were significantly higher compared to the first, at 85%, 77%, 62% versus 56%, 49%, 38% respectively (log-rank test P < 0·0001). On multivariate analysis, high-dose methotrexate (HD-MTX)-based induction protocols employed in the second era were associated with improved OS compared to those used in the first [hazard ratio (HR) 0·40, 95% confidence interval (CI) 0·28–0·57]. Within the second era, superior OS rates were seen with the use of intensive HD-MTX protocols (including consolidation with high-dose chemotherapy and autologous stem cell transplantation) compared to non-intensive HD-MTX schedules (HR 0·47, 95% CI 0·22–0·99). Initiating chemotherapy within 14 days of biopsy and use of rituximab were independently associated with improved OS and progression-free survival during the second era. These data suggest that prompt treatment initiation and use of intensive HD-MTX-and rituximab-based protocols have resulted in improved survival outcomes for patients.
- Published
- 2021
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