GRACIA APARECIDA MARTINEZ

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina

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  • conferenceObject
    Surveillance Functional Imaging Has Limited Role in Solitary Plasmacytomas: International Multi-Centre Study of Clinical Outcomes
    (2017) SHARPLEY, Faye A.; NEFFA, Pedro; PANITSAS, Fotis; KOTHARI, Jaimal; CUTTER, David; SZOR, Roberta Shcolnik; SUBESINGHE, Manil; MARTINEZ, Gracia; ROCHA, Vanderson; RAMASAMY, Karthik
  • conferenceObject
    Challenges in Diagnosis and Treatment of Systemic Amyloidosis: 10 Years of Experience in a Public Brazilian University Center
    (2020) SZOR, Roberta Shcolnik; FERNANDES, Fabio; SEGURO, Fernanda S.; LINO, Angelina M.; JORGE, Lecticia B.; MENDONCA, Leonardo O.; FEITOSA, Valkercyo A.; CASTELLI, Jussara B.; REGO, Eduardo M.; JACOMASSI, Mayara; ALVES, Lucas B. O.; MARTINEZ, Gracia; ROCHA, Vanderson
  • conferenceObject
    Treating multiple myeloma in a resource-limited setting: real-world outcomes
    (2022) MATINEZ, Gracia; SEGURO, Fernanda; JACOMASSI, Mayara; VISNADI, Helena; ATANAZIO, Marcelo; SZOR, Roberta; NEFFA, Pedro; PEREIRA, Thales; SILVA, Wellington; DORLHIAC, Pedro; VELASQUES, Rodrigo; BASSOLI, Lucas; ROCHA, Vanderson
  • article 3 Citação(ões) na Scopus
    Is it feasible to use granulocyte-colony stimulating factor alone to mobilize progenitor cells in multiple myeloma patients induced with a cyclophosphamide, thalidomide and dexamethasone regimen?
    (2016) CRUSOE, Edvan de Queiroz; HIGASHI, Fabiana; MARTINEZ, Gracia Aparecida; BARROS, José Carlos; BELLESSO, Marcelo; ROSSATO, Marina; MARRET, Ana Cinira F.; CHIATTONE, Carlos Sérgio; HUNGRIA, Vania Tietsch de Moraes
    ABSTRACT Background: Cyclophosphamide plus thalidomide as induction for multiple myeloma patients eligible for autologous stem cell transplantation may be a limiting factor for cell mobilization. The minimum acceptable mobilized peripheral blood stem cell count to prevent deleterious effects during transplantation is 2.0 × 106 CD34+ cells/kg. Combining other treatments to granulocyte-colony stimulating factor, such as cyclophosphamide, could overcome the mobilization limitation. The objective of this study was to assess the number of CD34+ cells mobilized using granulocyte-colony stimulating factor with and without cyclophosphamide after induction with cyclophosphamide, thalidomide and dexamethasone. Methods: A retrospective study was performed of a cohort of multiple myeloma patients submitted to autologous stem cell transplantations at two Brazilian centers between May 2009 and July 2013. The oral cyclophosphamide and thalidomide induction doses used were 1500 mg/month and 100-200 mg/day, respectively. Mobilization doses were 10-15 mcg/kg granulocyte-colony stimulating factor with 2-4 g/m2 cyclophosphamide, or 15-20 mcg/kg granulocyte-colony stimulating factor alone for 5 days. Collection of >2.0 × 106 CD34+ cells/kg was considered sufficient. Results: Eighty-eight patients were analyzed; only 18 received cyclophosphamide. The median age was 58 years old (range: 51-62) for the granulocyte-colony stimulating factor group and 56.5 years old (range: 54-60) for granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3, respectively. The group that received cyclophosphamide collected a higher median number of progenitor cells [3.8 (range: 3.1-4.4) vs. 3.2 (range: 2.3-3.8)] (p-value = 0.008). No correlation was observed between better responses or number of induction cycles and the number of cells collected. Conclusion: The number of cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide was higher. However, in both groups, the median number of CD34+ cells was sufficient to perform a single autologous stem cell transplantation; no deleterious effects were reported during harvesting.
  • conferenceObject
    Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma: Ikema Subgroup Analysis By Number of Prior Lines of Treatment
    (2022) CAPRA, Marcelo; MARTIN, Thomas; MOREAU, Philippe; MARTINEZ, Gracia; ORIOL, Albert; KOH, Youngil; QUACH, Hang; YONG, Kwee; RAWLINGS, Andreea; TEKLE, Christina; MACE, Sandrine; RISSE, Marie-Laure; SPICKA, Ivan
  • article 6 Citação(ões) na Scopus
    CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: Case report
    (2014) VASCONCELOS, Dewton de Moraes; BEITLER, Beatriz; MARTINEZ, Gracia A.; PEREIRA, Juliana; AMIGO FILHO, Jose Ulysses; KLAUTAU, Giselle Burlamaqui; LIAN, Yu Cheng; NEGRA, Marinella Della; DUARTE, Alberto Jose da Silva
    Leukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells. (C) 2014 Published by Elsevier Inc.
  • article 13 Citação(ões) na Scopus
    Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study
    (2023) MARTIN, Thomas; DIMOPOULOS, Meletios-Athanasios; MIKHAEL, Joseph; YONG, Kwee; CAPRA, Marcelo; FACON, Thierry; HAJEK, Roman; SPICKA, Ivan; BAKER, Ross; KIM, Kihyun; MARTINEZ, Gracia; MIN, Chang-Ki; POUR, Ludek; LELEU, Xavier; ORIOL, Albert; KOH, Youngil; SUZUKI, Kenshi; CASCA, France; MACE, Sandrine; RISSE, Marie-Laure; MOREAU, Philippe
    Longer-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 trial IKEMA (NCT03275285), in a prespecified, follow-up analysis of progression-free survival (PFS, primary study endpoint), final complete response (CR) using Hydrashift Isa immunofixation assay, minimal residual disease (MRD) negativity, and safety. Enrolled patients had relapsed/refractory multiple myeloma (1-3 prior treatment lines). Isa 10 mg/kg was administered intravenously weekly in cycle 1 then biweekly. Efficacy analyses were performed in the intent-to-treat population (Isa-Kd: n = 179, Kd: n = 123) and safety evaluated in treated patients (Isa-Kd: n = 177, Kd: n = 122). Consistent with the primary interim analysis, the addition of Isa to Kd prolonged PFS (HR 0.58, 95.4% CI: 0.42-0.79; median PFS 35.7 [95% CI: 25.8-44.0] vs 19.2 [95% CI: 15.8-25.0] months). PFS benefit was observed with Isa-Kd across subgroups, including patients with poor prognosis. The stringent CR/CR rate was 44.1% vs 28.5% (odds-ratio: 2.09, 95% CI: 1.26-3.48), the MRD negativity rate 33.5% vs 15.4% (odds-ratio: 2.78, 95% CI: 1.55-4.99) and the MRD negativity CR rate 26.3% vs 12.2%, with Isa-Kd vs Kd. The safety profile of Isa-Kd was similar to that reported in the prior interim analysis. These findings further support Isa-Kd as a standard-of-care treatment for relapsed multiple myeloma patients.
  • article 180 Citação(ões) na Scopus
    Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
    (2021) MOREAU, Philippe; DIMOPOULOS, Meletios-Athanasios; MIKHAEL, Joseph; YONG, Kwee; CAPRA, Marcelo; FACON, Thierry; HAJEK, Roman; SPICKA, Ivan; BAKER, Ross; KIM, Kihyun; MARTINEZ, Gracia; MIN, Chang-Ki; POUR, Ludek; LELEU, Xavier; ORIOL, Albert; KOH, Youngil; SUZUKI, Kenshi; RISSE, Marie-Laure; ASSET, Gaelle; MACE, Sandrine; MARTIN, Thomas
    Background Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, openlabel study compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple rnyeloma. Methods This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple rnyelorna aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received time approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285. Findings Between Nov 15,2017, and March 21,2019,302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19.15 months (95% CI 15.77-not reached) in the control group, with a hazard ratio of 0.53 (99% CI 0.32-0-89; one-sided p=0-0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEA Es led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEA Es during study treatment occurred in six (3%) versus four (3%) patients. Interpretation The addition of isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population.
  • conferenceObject
    Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed multiple myeloma (IKEMA): final overall survival analysis
    (2023) YONG, Kwee; MARTIN, Thomas; DIMOPOULOS, Meletios; MIKHAEL, Joseph; CAPRA, Marcelo; FACON, Thierry; HAJEK, Roman; SPICKA, Ivan; BAKER, Ross; KIM, Kihyun; MARTINEZ, Gracia; MIN, Chang-Ki; POUR, Ludek; LELEU, Xavier; ORIOL, Albert; KOH, Youngil; SUZUKI, Kenshi; CASCA, France; MACE, Sandrine; RISSE, Marie-Laure; MOREAU, Philippe
  • article 1 Citação(ões) na Scopus
    Systemic amyloidosis journey from diagnosis to outcomes: a twelve-year real-world experience of a single center in a middle-income country
    (2022) SZOR, Roberta Shcolnik; FERNANDES, Fabio; LINO, Angelina Maria Martins; MENDONCA, Leonardo Oliveira; SEGURO, Fernanda Salles; FEITOSA, Valkercyo Araujo; CASTELLI, Jussara Bianchi; JORGE, Lecticia Barbosa; ALVES, Lucas Bassolli de Oliveira; NEVES, Precil Diego Miranda de Menezes; SOUZA, Evandro de Oliveira; CAVALCANTE, Livia Barreira; MALHEIROS, Denise; KALIL, Jorge; MARTINEZ, Gracia Aparecida; ROCHA, Vanderson
    Background: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients' medical records were retrospectively reviewed. Results: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, & GE; 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had & GE; 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG & GE; 2 were identified as independent risk factors for reduced survival. Conclusions: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.