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Article ; Online: Soluble B-cell maturation antigen in multiple myeloma.

Costa, Bruno Almeida / Ortiz, Ricardo J / Lesokhin, Alexander M / Richter, Joshua

2024 Volume 99, Issue 4, Page(s) 727–738

Abstract: B-cell maturation antigen (BCMA) has emerged as a promising immunotherapeutic target in multiple myeloma (MM) management, with the successive approval of antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapies ... ...

Abstract	B-cell maturation antigen (BCMA) has emerged as a promising immunotherapeutic target in multiple myeloma (MM) management, with the successive approval of antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapies directed to this membrane receptor. Soluble BCMA (sBCMA), a truncated version produced through gamma-secretase cleavage, can be quantified in serum/plasma samples from patients with MM via electrochemiluminescence, fluorescence, or enzyme-linked immunosorbent assays, as well as through mass spectrometry-based proteomics. Besides its short serum half-life and independence from kidney function, sBCMA represents a reliable and convenient tool for MM monitoring in patients with nonsecretory or oligosecretory disease. Numerous studies have suggested a potential utility of this bioanalyte in the risk stratification of premalignant plasma cell disorders, diagnosis and prognostication of MM, and response evaluation following anti-myeloma therapies. In short, sBCMA might be the "Swiss army knife" of MM laboratory testing, but is it ready for prime time?
MeSH term(s)	Humans ; Multiple Myeloma/pathology ; B-Cell Maturation Antigen ; Immunotherapy, Adoptive ; Antibodies, Bispecific/therapeutic use ; Amyloid Precursor Protein Secretases
Chemical Substances	B-Cell Maturation Antigen ; Antibodies, Bispecific ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27225
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Article ; Online: Revisiting the role of alkylating agents in multiple myeloma: Up-to-date evidence and future perspectives.

Costa, Bruno Almeida / Mouhieddine, Tarek H / Ortiz, Ricardo J / Richter, Joshua

Critical reviews in oncology/hematology

2023 Volume 187, Page(s) 104040

Abstract: From the 1960s to the early 2000s, alkylating agents (e.g., melphalan, cyclophosphamide, and bendamustine) remained a key component of standard therapy for newly-diagnosed or relapsed/refractory multiple myeloma (MM). Later on, their associated ... ...

Abstract	From the 1960s to the early 2000s, alkylating agents (e.g., melphalan, cyclophosphamide, and bendamustine) remained a key component of standard therapy for newly-diagnosed or relapsed/refractory multiple myeloma (MM). Later on, their associated toxicities (including second primary malignancies) and the unprecedented efficacy of novel therapies have led clinicians to increasingly consider alkylator-free approaches. Meanwhile, new alkylating agents (e.g., melflufen) and new applications of old alkylators (e.g., lymphodepletion before chimeric antigen receptor T-cell [CAR-T] therapy) have emerged in recent years. Given the expanding use of antigen-directed modalities (e.g., monoclonal antibodies, bispecific antibodies, and CAR-T therapy), this review explores the current and future role of alkylating agents in different treatment settings (e.g., induction, consolidation, stem cell mobilization, pre-transplant conditioning, salvage, bridging, and lymphodepleting chemotherapy) to ellucidate the role of alkylator-based regimens in modern-day MM management.
MeSH term(s)	Humans ; Multiple Myeloma/drug therapy ; Multiple Myeloma/diagnosis ; Alkylating Agents/therapeutic use ; Receptors, Chimeric Antigen ; Cyclophosphamide ; Bendamustine Hydrochloride/therapeutic use
Chemical Substances	Alkylating Agents ; Receptors, Chimeric Antigen ; Cyclophosphamide (8N3DW7272P) ; Bendamustine Hydrochloride (981Y8SX18M)
Language	English
Publishing date	2023-05-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2023.104040
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Article ; Online: CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review.

Sadek, Norah Layla / Costa, Bruno Almeida / Nath, Karthik / Mailankody, Sham

Clinical pharmacology and therapeutics

2023 Volume 114, Issue 6, Page(s) 1184–1195

Abstract: The emergence of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, including multiple myeloma (MM). Two BCMA-directed CAR T-cell products - idecabtagene vicleucel (ide-cel) and ciltacabtagene ... ...

Abstract	The emergence of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, including multiple myeloma (MM). Two BCMA-directed CAR T-cell products - idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) - have received US Food and Drug Administration (FDA) approval for patients with relapsed/refractory MM who underwent four or more prior lines of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody). Despite producing unprecedented response rates in an otherwise difficult to treat patient population, CAR T-cell therapies are commonly associated with immune-related adverse events (e.g., cytokine release syndrome and neurotoxicity), cytopenias, and infections. Moreover, many patients continue to exhibit relapse post-treatment, with resistance mechanisms yet to be fully understood. Ongoing basic, translational, and clinical research efforts are poised to generate deeper insights into the optimal utilization of these therapies, improve their efficacy, minimize associated toxicity, and identify new target antigens in patients with MM.
MeSH term(s)	Humans ; Multiple Myeloma/therapy ; Immunotherapy, Adoptive/adverse effects ; Neoplasm Recurrence, Local ; Hematologic Neoplasms ; Antiviral Agents
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.3057
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Article ; Online: What's Old is New: The Past, Present and Future Role of Thalidomide in the Modern-Day Management of Multiple Myeloma.

Costa, Bruno Almeida / Mouhieddine, Tarek H / Richter, Joshua

Targeted oncology

2022 Volume 17, Issue 4, Page(s) 383–405

Abstract: Immunomodulatory drugs (IMiDs) have become an integral part of therapy for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM). IMiDs bind to cereblon, leading to the degradation of proteins involved in B-cell survival and proliferation. ...

Abstract	Immunomodulatory drugs (IMiDs) have become an integral part of therapy for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM). IMiDs bind to cereblon, leading to the degradation of proteins involved in B-cell survival and proliferation. Thalidomide, a first-generation IMiD, has little to no myelosuppressive potential, negligible renal clearance, and long-proven anti-myeloma activity. However, thalidomide's adverse effects (e.g., somnolence, constipation, and peripheral neuropathy) and the advent of more potent therapeutic options has led to the drug being less frequently used in many countries, including the US and Canada. Newer-generation IMiDs, such as lenalidomide and pomalidomide, are utilized far more frequently. In numerous previous trials, salvage therapy with thalidomide (50-200 mg/day) plus corticosteroids (with or without selected cytotoxic or targeted agents) has been shown to be effective and well-tolerated in the RRMM setting. Hence, thalidomide-based regimens remain important alternatives for heavily pretreated patients, especially for those who have no access to novel therapies and/or are not eligible for their use (due to renal failure, high-grade myelosuppression, or significant comorbidities). Ongoing and future trials may provide further insights into the current role of thalidomide, especially by comparing thalidomide-containing regimens with protocols based on newer-generation IMiDs and by investigating thalidomide's association with novel therapies (e.g., antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells).
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Immunologic Factors/adverse effects ; Lenalidomide/therapeutic use ; Multiple Myeloma/drug therapy ; Salvage Therapy ; Thalidomide/adverse effects
Chemical Substances	Antineoplastic Agents ; Immunologic Factors ; Thalidomide (4Z8R6ORS6L) ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2022-06-30
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	2222136-0
ISSN	1776-260X ; 1776-2596
ISSN (online)	1776-260X
ISSN	1776-2596
DOI	10.1007/s11523-022-00897-8
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Article ; Online: Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Costa, Bruno Almeida / Costa, Thomaz Alexandre / Saravia, Sara Diaz / Felix, Nicole / Tan, Carlyn Rose / Korde, Neha / Richter, Joshua

American journal of hematology

2024

Abstract: Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive ... ...

Abstract	Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27288
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Article ; Online: Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.

Costa, Bruno Almeida / Costa, Thomaz Alexandre / Pak, Kevin / Patel, Aesha / Felix, Nicole / Mouhieddine, Tarek H / Richter, Joshua

American journal of hematology

2024

Abstract: In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/ ...

Abstract	In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I
Language	English
Publishing date	2024-04-12
Publishing country	United States
Document type	Letter
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27314
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Article ; Online: Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.

Costa, Thomaz Alexandre / Felix, Nicole / Costa, Bruno Almeida / Godoi, Amanda / Nogueira, Alleh / Rossi, Adriana

British journal of haematology

2023 Volume 203, Issue 3, Page(s) 395–403

Abstract: Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to ...

Abstract	Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.
Language	English
Publishing date	2023-08-02
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19017
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Article ; Online: Durable Response after Olaparib Treatment for Perihilar Cholangiocarcinoma with Germline BRCA2 Mutation.

Costa, Bruno Almeida / Tallón de Lara, Paulino / Park, Wungki / Keane, Fergus / Harding, James J / Khalil, Danny N

Oncology research and treatment

2023 Volume 46, Issue 5, Page(s) 211–215

Abstract: Introduction: Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For ... ...

Abstract	Introduction: Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For instance, homologous recombination deficiency (HRD) has been considered a predictive biomarker of clinical response to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors. Case report: A 53-year-old man with a stage 3 (T4N0M0) BRCA2-mutant CCA developed intolerable toxicity after 44 cycles of gemcitabine/cisplatin. In light of his HRD positivity, treatment was switched to single-agent olaparib. The patient showed a partial radiological response, which was maintained after 8 months of olaparib discontinuation (progression-free survival >36 months). Conclusion: Given the durable response observed, olaparib can be a valuable therapeutic tool in BRCA-mutant CCAs. Ongoing and future clinical trials are needed to confirm the role of PARP inhibition in similar patients and to define the clinicopathological and molecular profile of the individuals most likely to benefit.
MeSH term(s)	Male ; Female ; Humans ; Middle Aged ; Poly(ADP-ribose) Polymerase Inhibitors/adverse effects ; Klatskin Tumor/drug therapy ; Ovarian Neoplasms/pathology ; Poly(ADP-ribose) Polymerases/genetics ; Poly(ADP-ribose) Polymerases/therapeutic use ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/genetics ; Bile Ducts, Intrahepatic/pathology ; Mutation ; Germ Cells/pathology ; BRCA2 Protein/genetics
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors ; olaparib (WOH1JD9AR8) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; BRCA2 protein, human ; BRCA2 Protein
Language	English
Publishing date	2023-03-07
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2760274-6
ISSN	2296-5262 ; 2296-5270
ISSN (online)	2296-5262
ISSN	2296-5270
DOI	10.1159/000529919
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Article ; Online: Nontyphoidal Salmonellosis Leading to Fatal Outcome in an Allogeneic Hematopoietic Stem Cell Transplant Recipient From Northeastern Brazil.

Costa, Bruno Almeida / Duarte, Fernando Barroso / Duarte, João Vitor Araújo / Duarte, Isabella Araújo / Barroso, Karine Sampaio Nunes / Gonçalves, Alexia Triandopolis

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

2023 Volume 21, Issue 5, Page(s) 477–480

MeSH term(s)	Humans ; Brazil/epidemiology ; Salmonella Infections/diagnosis ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation/adverse effects
Language	English
Publishing date	2023-04-19
Publishing country	Turkey
Document type	Letter
ZDB-ID	2396778-X
ISSN	2146-8427 ; 1304-0855
ISSN (online)	2146-8427
ISSN	1304-0855
DOI	10.6002/ect.2022.0317
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Article ; Online: Can SARS-CoV-2 induce hematologic malignancies in predisposed individuals? A case series and review of the literature.

Costa, Bruno Almeida / da Luz, Kaiza Vilarinho / Campos, Sarah Emanuelle Viana / Lopes, Germison Silva / Leitão, João Paulo de Vasconcelos / Duarte, Fernando Barroso

Hematology, transfusion and cell therapy

2022 Volume 44, Issue 1, Page(s) 26–31

Abstract: Introduction: Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin- ... ...

Abstract	Introduction: Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. Methods: This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. Main results: Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous Conclusion: Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.
Language	English
Publishing date	2022-01-19
Publishing country	Brazil
Document type	Journal Article
ISSN	2531-1387
ISSN (online)	2531-1387
DOI	10.1016/j.htct.2021.11.015
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