JavaScript NENÍ povolen !

Prosím povolte JavaScript.

* Zobrazit nápovědu

Reset

MeSH: bortezomib-terapeutické užití

36 záznamů v PubMed Filtry

Článek

Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma

Dimopoulos, Meletios Athanasios
Autor Dimopoulos, Meletios Athanasios From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Beksac, Meral
Autor Beksac, Meral From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Pour, Ludek
Autor Pour, Ludek From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Delimpasi, Sosana
Autor Delimpasi, Sosana From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Vorobyev, Vladimir
Autor Vorobyev, Vladimir From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Quach, Hang
Autor Quach, Hang From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Spicka, Ivan
Autor Spicka, Ivan From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Radocha, Jakub
Autor Radocha, Jakub From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Robak, Pawel
Autor Robak, Pawel From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)
Kim, Kihyun
Autor Kim, Kihyun From the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens (M.A.D.), and General Hospital Evangelismos (S.D.) - both in Athens; the Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Turkey (M.B.); the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the First Faculty of Medicine, Charles University, and General Hospital, Prague (I.S.), and the Fourth Department of Internal Medicine-Hematology, University Hospital Hradec Králové, and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (J.R.) - all in the Czech Republic; Leningrad Regional Clinical Hospital, Saint Petersburg, Russia (V.V.); the University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); Medical University of Lodz, Łódź, Poland (P.R.); Sungkyunkwan University and Samsung Medical Center, Seoul, South Korea (K.K.); IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, and Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy (M.C.); the Division of Clinical Oncology-Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo (K.S.); GSK, Durham, NC (K.M.); GSK, Philadelphia (F.P.), and GSK, Collegeville (N.S., B.E.K., J.O.) - both in Pennsylvania; GSK, Stevenage, United Kingdom (A.P.-J.); GSK, Waltham, MA (X.L.Z., G.F.); the Hematology Department, Cancer Research Center-Instituto de Investigación Biomédica de Salamanca, University Hospital of Salamanca, Salamanca, Spain (M.-V.M.); and the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto (S.T.)

The New England journal of medicine. 2024 Aug 01 ; 391 (5) : 408-421. [epub] 20240602

N Engl J Med
ISSN 1533-4406 | 0028-4793
Zdroj

BACKGROUND: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse. METHODS: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed. RESULTS: A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group. CONCLUSIONS: Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.).

Článek

Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma

The New England journal of medicine. 2024 Aug 01 ; 391 (5) : 393-407. [epub] 20240601

N Engl J Med
ISSN 1533-4406 | 0028-4793
Zdroj

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Článek

ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study

Haematologica. 2024 Mar 01 ; 109 (3) : 867-876. [epub] 20240301

ISSN 1592-8721 | 0390-6078
Zdroj

Melphalan flufenamide (melflufen), a first-in-class, alkylating peptide-drug conjugate, demonstrated clinical benefit in combination with dexamethasone in triple-class refractory multiple myeloma (MM). The phase I/IIa ANCHOR study evaluated melflufen (30 or 40 mg) and dexamethasone (40 mg with daratumumab; 20 mg followed by 40 mg with bortezomib; dose reduced if aged ≥75 years) in triplet combination with daratumumab (16 mg/kg; daratumumab arm) or bortezomib (1.3 mg/m2; bortezomib arm) in patients with relapsed/refractory MM refractory to an immunomodulatory agent and/or a proteasome inhibitor and who had received one to four prior lines of therapy. Primary objectives were to determine the optimal dose of melflufen in triplet combination (phase I) and overall response rate (phase IIa). In total, 33 patients were treated in the daratumumab arm and 23 patients received therapy in the bortezomib arm. No dose-limiting toxicities were reported at either melflufen dose level with either combination. With both triplet regimens, the most common grade ≥3 treatment-emergent adverse events were thrombocytopenia and neutropenia; thrombocytopenia was the most common treatment-emergent adverse event leading to treatment discontinuation. In the daratumumab arm, patients receiving melflufen 30 mg remained on treatment longer than those receiving the 40-mg dose. In the daratumumab arm, the overall response rate was 73% and median progression-free survival was 12.9 months. Notably, in the bortezomib arm, the overall response rate was 78% and median progression-free survival was 14.7 months. Considering the totality of the data, melflufen 30 mg was established as the recommended dose for use with dexamethasone and daratumumab or bortezomib for future studies in relapsed/refractory MM.

MeSH
bortezomib terapeutické užití MeSH
dexamethason terapeutické užití MeSH
fenylalanin * analogy a deriváty MeSH
lidé MeSH
melfalan * analogy a deriváty MeSH
mnohočetný myelom * diagnóza farmakoterapie MeSH
monoklonální protilátky * MeSH
nádory plazmocelulární * MeSH
neutropenie * chemicky indukované MeSH
protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
senioři MeSH
trombocytopenie * MeSH
Check Tag
lidé MeSH
senioři MeSH
Publikační typ
časopisecké články MeSH
klinické zkoušky, fáze I MeSH
klinické zkoušky, fáze II MeSH
Názvy látek
bortezomib MeSH
daratumumab MeSH Prohlížeč
dexamethason MeSH
fenylalanin * MeSH
melfalan * MeSH
melflufen MeSH Prohlížeč
monoklonální protilátky * MeSH

Článek

NK92 Expressing Anti-BCMA CAR and Secreted TRAIL for the Treatment of Multiple Myeloma: Preliminary In Vitro Assessment

Cells. 2023 Nov 30 ; 12 (23) : . [epub] 20231130

ISSN 2073-4409
Zdroj

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the piggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45.1% (±26.1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and γ-secretase inhibitors (GSIs), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrates the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy.

Klíčová slova
allogenic, cancer, chimeric antigen receptor, immunotherapy, multiple myeloma, natural killer,
MeSH
bortezomib farmakologie terapeutické užití MeSH
chimerické antigenní receptory * metabolismus MeSH
imunoterapie adoptivní MeSH
kvalita života MeSH
lidé MeSH
maturační antigen B-buněk metabolismus MeSH
mnohočetný myelom * patologie terapie MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
bortezomib MeSH
chimerické antigenní receptory * MeSH
maturační antigen B-buněk MeSH

Článek

Switching to daratumumab SC from IV is safe and preferred by patients with multiple myeloma

Journal of oncology pharmacy practice. 2023 Jul ; 29 (5) : 1172-1177. [epub] 20220906

J Oncol Pharm Pract
ISSN 1477-092X | 1078-1552
Zdroj

INTRODUCTION: Two phase 3 studies demonstrated superior efficacy of intravenous daratumumab (DARA IV) plus bortezomib/melphalan/prednisone (ALCYONE) or lenalidomide/dexamethasone (Rd; MAIA) versus standard-of-care regimens for transplant-ineligible newly diagnosed multiple myeloma. In these studies, patients could switch from DARA IV to subcutaneous daratumumab (DARA SC) while receiving daratumumab monotherapy in ALCYONE (as of Cycle 11) or daratumumab plus Rd in MAIA. The phase 3 COLUMBA study demonstrated noninferiority of DARA SC to DARA IV. DARA SC reduced administration time, allowing patients to spend less time in healthcare settings, a relevant practical consideration for patient care in the COVID-19 pandemic/settings of limited healthcare resources. METHODS: DARA SC 1800 mg was administered every 4 weeks, per approved dosing schedules. We evaluated safety and patient-reported experience (ALCYONE only) among patients who switched from DARA IV to DARA SC. RESULTS: Fifty-seven patients in ALCYONE and 135 in MAIA switched to DARA SC. Three (2.2%; MAIA) patients reported injection-site reactions, all of which were mild. No infusion-related reactions occurred with DARA SC. In ALCYONE, >80% of patients preferred DARA SC over DARA IV. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 5.3% of patients in ALCYONE and 25.9% in MAIA; one (0.7%; MAIA) patient experienced a TEAE with an outcome of death. CONCLUSION: For transplant-ineligible newly diagnosed multiple myeloma, DARA SC (monotherapy/with Rd) was safe and preferred over DARA IV. ClinicalTrials.gov, NCT02195479/NCT02252172.

Klíčová slova
Multiple myeloma, daratumumab, intravenous, subcutaneous, transplant-ineligible,
MeSH
bortezomib terapeutické užití MeSH
COVID-19 * MeSH
lidé MeSH
mnohočetný myelom * farmakoterapie MeSH
pandemie MeSH
protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
klinické zkoušky, fáze III MeSH
Názvy látek
bortezomib MeSH
daratumumab MeSH Prohlížeč

Článek

Novel Local "Off-the-Shelf" Immunotherapy for the Treatment of Myeloma Bone Disease

Cells. 2023 Jan 30 ; 12 (3) : . [epub] 20230130

ISSN 2073-4409
Zdroj

Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient "off-the-shelf" ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (~60%) within in vitro 3D model of MBD. Furthermore, NKs' post-thawing cytotoxic activity is significantly enhanced (~75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic "off-the-shelf" approach to improve the outcomes of patients suffering from MBD.

Klíčová slova
cancer, fibrin, immunotherapy, local treatment, myeloma bone disease, natural killers,
MeSH
bortezomib terapeutické užití MeSH
imunoterapie MeSH
mnohočetný myelom * farmakoterapie MeSH
myši MeSH
nádorové buněčné linie MeSH
nemoci kostí * terapie MeSH
zvířata MeSH
Check Tag
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
bortezomib MeSH

Článek

The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018

Blood cancer journal. 2023 Jan 25 ; 13 (1) : 19. [epub] 20230125

Blood Cancer J
ISSN 2044-5385
Zdroj

Systemic light-chain (AL) amyloidosis is a rare and debilitating disease. Advances have been made in new treatments in recent years, yet real-world data on the management of the disease are scarce. EMN23 is a retrospective, observational study of patients who initiated first-line treatment in 2004-2018 in Europe, presenting the demographics, clinical characteristics, treatment patterns, and outcomes, from 4480 patients. Regimens based on bortezomib were the most frequently used as first-line therapy; only 6.2% of the patients received autologous stem cell transplant. Hematologic responses improved post-2010 (67.1% vs 55.6% pre-2010). The median overall survival (OS) was 48.8 (45.2-51.7) months; 51.4 (47.3-57.7) months pre-2010 and 46.7 (41.3-52.2) months post-2010. Early mortality was 13.4% and did not improve (11.4% vs 14.4% pre- and post-2010); furthermore, it remained high in patients with advanced cardiac disease (over 39% for stage IIIb). There was a significant improvement for stage IIIa (14.2 vs 30.7 months, p = 0.0170) but no improvement for stage IIIb patients (5.0 vs 4.5 months). This European real-world study of AL-amyloidosis emphasizes the unmet needs of early diagnosis, and the lack of improvement in survival outcomes of the frail stage IIIb population, despite the introduction of new therapies in recent years.

MeSH
bortezomib terapeutické užití MeSH
lidé MeSH
primární amyloidóza * diagnóza terapie MeSH
retrospektivní studie MeSH
transplantace kmenových buněk MeSH
výsledek terapie MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
pozorovací studie MeSH
práce podpořená grantem MeSH
Geografické názvy
Evropa epidemiologie MeSH
Názvy látek
bortezomib MeSH

Článek

The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma

Nature communications. 2022 Nov 10 ; 13 (1) : 6820. [epub] 20221110

Nat Commun
ISSN 2041-1723
Zdroj

Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n = 4146), we observe no correlation between serum Ig levels and patient survival, while amount of intracellular Ig has a strong predictive effect. Focused CRISPR screen, transcriptional and proteomic analysis identify deubiquitinase OTUD1 as a critical mediator of Ig synthesis, proteasome inhibitor sensitivity and tumor burden in MM. Mechanistically, OTUD1 deubiquitinates peroxiredoxin 4 (PRDX4), protecting it from endoplasmic reticulum (ER)-associated degradation. In turn, PRDX4 facilitates Ig production which coincides with the accumulation of unfolded proteins and higher ER stress. The elevated load on proteasome ultimately potentiates myeloma response to proteasome inhibitors providing a window for a rational therapy. Collectively, our findings support the significance of the Ig production machinery as a biomarker and target in the combinatory treatment of MM patients.

MeSH
apoptóza MeSH
bortezomib farmakologie terapeutické užití MeSH
deubikvitinasy MeSH
imunoglobuliny MeSH
inhibitory proteasomu * farmakologie MeSH
lidé MeSH
mnohočetný myelom * farmakoterapie genetika metabolismus MeSH
proteasomový endopeptidasový komplex metabolismus MeSH
proteomika MeSH
specifické proteázy ubikvitinu MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
bortezomib MeSH
deubikvitinasy MeSH
imunoglobuliny MeSH
inhibitory proteasomu * MeSH
OTUD1 protein, human MeSH Prohlížeč
proteasomový endopeptidasový komplex MeSH
specifické proteázy ubikvitinu MeSH

Článek

Slow increase of bilirubin concentration during administration of lenalidomide, bortezomib and dexamethasone for multiple myeloma (unmasking previously undiagnosed Gilbert syndrome) and disappearance of necrobiotic xanthogranuloma after complete remission of multiple myeloma

Klinicka onkologie. 2022 Summer ; 35 (4) : 315-322.

Klin Onkol
ISSN 1802-5307 | 0862-495X
Zdroj

BACKGROUND: Lenalidomid ranks among immunomodulatory drugs. There are a few of the more common side effects, like a higher risk of venous trombembolism or diarrhea. Other side effects are rare. The hyperbilirubinemia described in this article can be assigned to them. In our case, the increase of bilirubin was associated with unrecognized Gilbert syndrome. CASE DESCRIPTION: We report a patient with multiple myeloma and necrobio-tic xanthogranuloma (NXG) of the skin and liver. After the treatment with bortezomib, lenalidomid and dexamethasone, complete remission was attained after 4 cycles with decrease of monoclonal immunoglobulin to an unmeasurable concentration. At the same time, the dis-appearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT was evident. The administration of bortezomib was stopped after 8 cycles and only continued with lenalidomide as a maintenance therapy. However, after four cycles of this therapy, bilirubin increased above the upper limit and the increase continued till the 11th month of lenadomide administration, when bilirubin reached the highest concentration of 75 μmol/l (more than the three-fold of the upper limit, grade III toxicity). The patient had asymptomatic hyperbilirubinemia with no underlying liver disease or renal impairment while being on lenalidomide therapy. Genetic studies proved mutation; insertion in the promotor gene UGT1A1 typical for Gilbert syndrome. Hyperbilirubinemia may be attributed to the unmasking of previously undia-gnosed Gilbert syndrome. Therefore, the therapy with lenalidomide was interrupted after 11 months. The bilirubin level decreased after the discontinuation of the drug. CONCLUSION: NXG disappeared after fulfilling complete remission of multiple myeloma with disappearance of monoclonal immunoglobulin. This observation supports the hypothesis that monoclonal immunoglobulin has a crucial role in the ethiopathogenesis of NXG and suggests the treatment of monoclonal gammopathy if present in a patient with NXG, hoping that this will result in xantogranuloma disappearance.

Klíčová slova
Gilbert syndrome, Kahler-Pick law, Multiple myeloma, hyperbilirubinemia, monoclonal Gilbert syndrome, necrobiotic xanthogranuloma,
MeSH
bilirubin MeSH
bortezomib terapeutické užití MeSH
dexamethason terapeutické užití MeSH
Gilbertova nemoc * farmakoterapie MeSH
hyperbilirubinemie farmakoterapie MeSH
lenalidomid terapeutické užití MeSH
lidé MeSH
mnohočetný myelom * farmakoterapie patologie MeSH
nekrobiotický xantogranulom * diagnóza farmakoterapie MeSH
PET/CT MeSH
protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
kazuistiky MeSH
Názvy látek
bilirubin MeSH
bortezomib MeSH
dexamethason MeSH
lenalidomid MeSH

Článek

A case of cutaneous collagenous vasculopathy associated with multiple myeloma and with a pathogenic variant of the glucocerebrosidase gene

Journal of cutaneous pathology. 2022 Aug ; 49 (8) : 717-721. [epub] 20220323

J Cutan Pathol
ISSN 1600-0560 | 0303-6987
Zdroj

Cutaneous collagenous vasculopathy (CCV) is an extremely rare acquired microangiopathy of unknown etiology. The authors describe a case of a 68-year-old man, a carrier of a heterozygous pathogenic variant of the glucocerebrosidase (GBA) gene, who was diagnosed with CCV, revealing uncommon fibrinogen positivity in direct immunofluorescence. The patient was subsequently diagnosed with multiple myeloma. Treatment of the myeloma with combined chemotherapy including bortezomib, followed by autologous stem cell transplantation, led to significant reduction of cutaneous lesions. To the best of the authors' knowledge, this is the first published case of CCV in a carrier of a pathogenic variant of the GBA gene, associated with multiple myeloma and with significant regression of CCV after myeloma treatment. Direct immunofluorescence examination revealed an unusual fibrinogen deposition. Hypothetical causative role of bortezomib treatment was proposed regarding significant regression of CCV.

Klíčová slova
bortezomib, cutaneous collagenous vasculopathy, direct immunofluorescence, glucocerebrosidase gene, multiple myeloma,
MeSH
autologní transplantace MeSH
bortezomib terapeutické užití MeSH
fibrinogen terapeutické užití MeSH
glukosylceramidasa terapeutické užití MeSH
kožní cévní nemoci * patologie MeSH
lidé MeSH
mnohočetný myelom * komplikace farmakoterapie genetika MeSH
protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
senioři MeSH
teleangiektazie * patologie MeSH
transplantace hematopoetických kmenových buněk * MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
Publikační typ
kazuistiky MeSH
Názvy látek
bortezomib MeSH
fibrinogen MeSH
glukosylceramidasa MeSH

* Zobrazit nápovědu

Upřesnit dle MeSH