10 results on '"Giralt SA"'
Search Results
2. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses.
- Author
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Ailawadhi S, Arnulf B, Patel KK, Cavo M, Nooka AK, Manier S, Callander NS, Costa LJ, Vij R, Bahlis NJ, Moreau P, Solomon SR, Abrahamsen IW, Baz RC, Broijl A, Chen C, Jagannath S, Raje N, Scheid C, Delforge M, Benjamin R, Pabst T, Iida S, Berdeja JG, Giralt SA, Truppel-Hartmann A, Chen Y, Zhong X, Wu F, Piasecki J, Eliason L, Dhanda DS, Felten J, Caia A, Cook M, Popa-Mckiver M, and Rodriguez-Otero P
- Abstract
Outcomes are poor in triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). In the phase 3 KarMMa-3 (clinicaltrials.gov; NCT03651128) trial, patients with TCE RRMM and 2-4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary endpoint; 13.3 vs 4.4 months; P<.0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio (HR), 0.49; 95% confidence interval (CI), 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median (95% CI) was 41.4 (30.9-not reached [NR]) vs 37.9 (23.4-NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE RRMM. NCT03651128., (Copyright © 2024 American Society of Hematology.)
- Published
- 2024
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3. A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma.
- Author
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Lendvai N, Hilden P, Devlin S, Landau H, Hassoun H, Lesokhin AM, Tsakos I, Redling K, Koehne G, Chung DJ, Schaffer WL, and Giralt SA
- Subjects
- Aged, Aged, 80 and over, Boronic Acids therapeutic use, Bortezomib, Disease Progression, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Lenalidomide, Male, Middle Aged, Multiple Myeloma genetics, Oligopeptides adverse effects, Pyrazines therapeutic use, Risk Factors, Thalidomide analogs & derivatives, Thalidomide therapeutic use, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone administration & dosage, Multiple Myeloma drug therapy, Oligopeptides administration & dosage
- Abstract
Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is safe and effective in relapsed or refractory multiple myeloma (R/RMM). We report phase 2 results of carfilzomib 20 mg/m(2) on days 1 to 2 of cycle 1, 56 mg/m(2) thereafter (30-minute infusion), in R/RMM with the option of adding dexamethasone (20 mg) for suboptimal response/progression. Forty-four patients enrolled, all having prior bortezomib and immunomodulatory drugs and a median of 5 prior regimens. Of 42 response-evaluable patients, 23 (55%) achieved at least partial response (PR). Median (95% confidence interval) duration of response, progression-free, and overall survival were 11.7 (6.7-14.7), 4.1 (2.5-11.8), and 20.3 months (6.4-not estimable), respectively. High-risk cytogenetics did not impact outcomes. Treatment was active in bortezomib-refractory subgroups, but these patients tended to have poorer outcomes. Four/10 patients with prior allogeneic transplant achieved at least PR. Of 6 patients who responded, progressed and had dexamethasone added, 4 achieved at least stable disease. The most frequent grade 3/4 adverse events (AEs) possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to AEs. Carfilzomib 56 mg/m(2) ± dexamethasone was tolerable and provided durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01351623., (© 2014 by The American Society of Hematology.)
- Published
- 2014
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4. Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma.
- Author
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Tam CS, Bassett R, Ledesma C, Korbling M, Alousi A, Hosing C, Kebraei P, Harrell R, Rondon G, Giralt SA, Anderlini P, Popat U, Pro B, Samuels B, Hagemeister F, Medeiros LJ, Champlin RE, and Khouri IF
- Subjects
- Adult, Aged, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Feasibility Studies, Female, Humans, Lymphoma, Mantle-Cell mortality, Male, Middle Aged, Prognosis, Radiotherapy Dosage, Retrospective Studies, Risk Factors, Rituximab, Survival Rate, Transplantation, Autologous, Treatment Outcome, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation, Lymphoma, Mantle-Cell therapy, Transplantation Conditioning
- Abstract
In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n = 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versus-host disease. Our results show that long-term disease-free survival in mantle cell lymphoma is possible after rituximab-containing autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.
- Published
- 2009
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5. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia.
- Author
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Lee SJ, Kukreja M, Wang T, Giralt SA, Szer J, Arora M, Woolfrey AE, Cervantes F, Champlin RE, Gale RP, Halter J, Keating A, Marks DI, McCarthy PL, Olavarria E, Stadtmauer EA, Abecasis M, Gupta V, Khoury HJ, George B, Hale GA, Liesveld JL, Rizzieri DA, Antin JH, Bolwell BJ, Carabasi MH, Copelan E, Ilhan O, Litzow MR, Schouten HC, Zander AR, Horowitz MM, and Maziarz RT
- Subjects
- Adolescent, Adult, Aged, Benzamides, Child, Child, Preschool, Disease-Free Survival, Female, HLA Antigens metabolism, Humans, Imatinib Mesylate, Male, Middle Aged, Registries, Treatment Outcome, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Piperazines therapeutic use, Pyrimidines therapeutic use
- Abstract
Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM(+)) and 900 subjects who did not receive IM before HCT (IM(-)) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM(+) and IM(-) groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.
- Published
- 2008
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6. Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation.
- Author
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Donato ML, Feasel AM, Weber DM, Prieto VG, Giralt SA, Champlin RE, and Duvic M
- Subjects
- Adult, Aged, Dose-Response Relationship, Drug, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Myxedema pathology, Palliative Care, Remission Induction, Scleroderma, Limited pathology, Scleroderma, Systemic pathology, Transplantation, Autologous, Treatment Outcome, Antineoplastic Agents, Alkylating administration & dosage, Hematopoietic Stem Cell Transplantation, Melphalan administration & dosage, Myxedema therapy, Scleroderma, Limited therapy, Scleroderma, Systemic therapy
- Abstract
Scleromyxedema, the most severe manifestation of the spectrum of lichen myxedematosus, is characterized by cutaneous mucinosis, extracutaneous manifestations, and a monoclonal gammopathy. Seven of 8 patients evaluated at our center were treated with high-dose melphalan (180 mg/m(2) intravenously) and autologous peripheral blood stem cell transplantation, with marked improvement of gastrointestinal, central nervous system, pulmonary manifestations, and Karnofsky performance status. Five patients obtained a cutaneous complete remission and 2 patients had partial remissions. Three patients with slight progression in the skin at 12, 8, and 4 months after treatment received a second cycle of high-dose melphalan and had further symptomatic improvement. The lichen myxedematosus-scleromyxedema spectrum appears to be a continuum that requires the presence of a serum paraprotein and differs in severity of skin lesions, extracutaneous manifestations, and performance status. High-dose melphalan followed by autologous transplantation appears effective for improving the symptoms and systemic manifestations of scleromyxedema.
- Published
- 2006
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7. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors.
- Author
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Ueno NT, Cheng YC, Rondón G, Tannir NM, Gajewski JL, Couriel DR, Hosing C, de Lima MJ, Anderlini P, Khouri IF, Booser DJ, Hortobagyi GN, Pagliaro LC, Jonasch E, Giralt SA, and Champlin RE
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols toxicity, Breast Neoplasms mortality, Breast Neoplasms pathology, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell pathology, Female, Graft vs Host Disease drug therapy, Graft vs Host Disease prevention & control, Graft vs Tumor Effect, Humans, Male, Melphalan administration & dosage, Middle Aged, Neoplasm Metastasis therapy, Peripheral Blood Stem Cell Transplantation mortality, Remission Induction, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms therapy, Carcinoma, Renal Cell therapy, Peripheral Blood Stem Cell Transplantation methods, Transplantation Chimera, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
We evaluated the feasibility and efficacy of a reduced-intensity conditioning (RIC) regimen of fludarabine and melphalan to achieve rapid complete donor chimerism after allogeneic stem cell transplantation (SCT) in patients with metastatic solid tumors. Between January 1999 and January 2003, 8 patients with metastatic breast cancer (BC) and 15 with metastatic renal cell carcinoma (RCC) underwent allogeneic SCT after an RIC regimen of 5 days of fludarabine and 2 days of melphalan. Filgrastim-mobilized stem cells from HLA-identical related or unrelated donors were infused. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus and methotrexate. All 22 evaluable patients had 100% donor chimerism at day 30 and at all measurement times thereafter. One patient died 19 days after SCT. Nine patients (39%) had grades II to IV acute GVHD and 10 patients (43%) had chronic GVHD. Five patients (22%) died of nonrelapse treatment-related complications. Treatment-related disease response was seen in 10 patients (45%), with 3 complete responses, 2 partial responses, and 5 minor responses. Fludarabine-melphalan is a feasible and effective RIC regimen for allogeneic SCT in metastatic BC and RCC. It induces rapid complete donor chimerism without the need for donor lymphocyte infusion. Tumor regression associated with GVHD is consistent with graft-versus-tumor effect.
- Published
- 2003
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8. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years.
- Author
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Wong R, Giralt SA, Martin T, Couriel DR, Anagnostopoulos A, Hosing C, Andersson BS, Cano P, Shahjahan M, Ippoliti C, Estey EH, McMannis J, Gajewski JL, Champlin RE, and de Lima M
- Subjects
- Age Factors, Aged, Disease-Free Survival, Female, Graft vs Host Disease prevention & control, Histocompatibility Testing, Humans, Male, Middle Aged, Neutrophils metabolism, Prognosis, Quality of Life, Time Factors, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Hematopoietic stem cell transplantation from unrelated donors is an effective treatment for myeloid malignancies, but its use is usually restricted to young patients without comorbidities. The development of reduced-intensity preparative regimens has allowed the extension of this form of treatment to older and medically infirm patients. We assessed the outcomes of patients older than 54 years who received unrelated donor transplants for the treatment of myeloid malignancies in our institution. There were 29 patients (median age, 59 years) with advanced acute myeloid leukemia (n = 13), myelodysplastic syndrome (n = 7), and chronic myeloid leukemia (n = 9) included. With a median follow-up of 27 months, the probability of overall and event-free survival, and nonrelapse mortality at one year were 44%, 37%, and 55%, respectively. Grades II to IV acute graft-versus-host disease (GVHD) occurred in 41% of patients and chronic GVHD developed in 63% of patients surviving more than 100 days. Of the 11 survivors, 9 were interviewed and reported good quality of life after transplantation using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) questionnaire, with high scores in all dimensions. Unrelated donor transplantation is a treatment option for older patients with myeloid malignancies. The results in this cohort of patients are comparable with those reported in younger patients with similarly advanced disease.
- Published
- 2003
- Full Text
- View/download PDF
9. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia.
- Author
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Kantarjian HM, O'Brien S, Cortes JE, Giralt SA, Rios MB, Shan J, Giles FJ, Thomas DA, Faderl S, De Lima M, Garcia-Manero G, Champlin R, Arlinghaus R, and Talpaz M
- Subjects
- Administration, Oral, Adult, Benzamides, Combined Modality Therapy, Female, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Protein-Tyrosine Kinases antagonists & inhibitors, Recurrence, Survival Analysis, Transplantation, Homologous, Antineoplastic Agents administration & dosage, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Piperazines administration & dosage, Pyrimidines administration & dosage
- Abstract
Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD.
- Published
- 2002
10. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality.
- Author
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Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, and Champlin RE
- Subjects
- Adult, Aged, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Murine-Derived, Cyclophosphamide administration & dosage, Female, Graft Survival, Graft vs Host Disease prevention & control, Graft vs Tumor Effect, Humans, Immunosuppressive Agents administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Lymphoma, Follicular mortality, Lymphoma, Follicular therapy, Male, Methotrexate therapeutic use, Middle Aged, Platelet Transfusion, Recurrence, Remission Induction, Rituximab, Tacrolimus therapeutic use, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Graft vs Host Disease epidemiology, Hematopoietic Stem Cell Transplantation, Immunotherapy, Adoptive, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 days or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.
- Published
- 2001
- Full Text
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