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1.
Cancer Immunol Immunother ; 73(7): 135, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758239

RESUMO

BACKGROUND: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab. OBJECTIVE: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment. METHODS: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment. RESULTS: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/µL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen. CONCLUSION: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Linfócitos , Monócitos , Mieloma Múltiplo , Talidomida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Feminino , Masculino , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/administração & dosagem , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Monócitos/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Adulto , Idoso de 80 Anos ou mais , Prognóstico
2.
Ann Hematol ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492020

RESUMO

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

3.
Pestic Biochem Physiol ; 198: 105745, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225088

RESUMO

Schoenoplectiella juncoides, a noxious sedge weed in Japanese rice paddy, has two ALS genes, and ALS-inhibitor-resistant plants have a mutation in one of the ALS genes. The authors aimed (a) to quantitate the effect of the number of mutant alleles of ALS genes on whole-plant resistance of S. juncoides and (b) to clarify a mode of inheritance of the resistance by investigating resistance levels of the progenies of a hybrid between two S. juncoides plants with Trp574Leu substitution in different ALS. A dose-response analysis on the parental lines and the F1 population suggested that the two ALS genes contribute equally to whole-plant resistant levels. A dose-response study on the F2 population indicated that it could be classified into five groups based on the sensitivities to metsulfuron-methyl. The five groups (in ascending order of resistance levels) were considered to have zero, one, two, three, and four mutant alleles. The stacking effect of mutant alleles on resistance enhancement was more significant when the number of mutant alleles was low than when it was high; in other words, each additional mutant allele stacking increases plant resistance, but the effect saturates as the number of mutant alleles increases. A chi-square test supported that the segregation ratio of the five groups corresponds to 1:4:6:4:1 of Mendelian independence for the two ALS loci.


Assuntos
Acetolactato Sintase , Cyperaceae , Herbicidas , Lixívia , Lixívia/farmacologia , Cyperaceae/genética , Herbicidas/farmacologia , Mutação , Alelos , Resistência a Herbicidas/genética , Acetolactato Sintase/genética
4.
Hematol Oncol ; 39(3): 349-357, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33724498

RESUMO

The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.


Assuntos
Bases de Dados Factuais , Lenalidomida/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
5.
Eur J Haematol ; 106(4): 555-562, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33476404

RESUMO

OBJECTIVES: This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). METHODS: We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. RESULT: At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)-based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide-refractory patients had significantly lower PFS than lenalidomide-sensitive patients, who were comparable to TOURMALINE-MM1 study. The patients with IgG type had significantly better PFS and OS than those with non-IgG type. CONCLUSION: This study presents the largest real-world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE-MM1 study, and IRd showed poor efficacy, especially in the non-IgG type and lenalidomide-refractory patients with RRMM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Compostos de Boro/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Glicina/administração & dosagem , Glicina/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
6.
Chemotherapy ; 66(5-6): 192-195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710867

RESUMO

The phase 3 ICARIA-MM trial showed that the addition of isatuximab improved the progression-free survival compared with pomalidomide/dexamethasone. However, the safety and efficacy of isatuximab for end-stage renal failure remains unclear. A 67-year-old man who started hemodialysis 5 years ago for diabetic nephropathy was diagnosed with International Staging System stage III multiple myeloma (MM) of IgD-λ type 3 years ago. After receiving a total of 7 treatment regimens, his free light chain (FLC) λ level increased from 419 to 2,070 mg/L, indicating progressive disease. Twelve days after starting isatuximab plus pomalidomide (3 mg daily) and dexamethasone (IsaPd), his FLC λ level rapidly decreased to 412 mg/L. The patient has now completed 7 courses of IsaPd with no adverse events, including infusion reactions and neutropenia. Isatuximab requires a lower dilution volume than daratumumab and can be safely and effectively administered to hemodialysis-dependent MM patients.


Assuntos
Mieloma Múltiplo , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Humanos , Masculino , Mieloma Múltiplo/tratamento farmacológico , Diálise Renal
7.
Ann Hematol ; 99(5): 1063-1072, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32248251

RESUMO

These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rates (ORRs), and safety. Eighty-three eligible patients were enrolled between October 2012 and August 2014. The median PFS was 28.0 months (95% CI 19.6-36.7) and the median OS was 55.3 months (95% CI 51.6-NA). Among the patients who received lenalidomide maintenance therapy, median PFS was significantly improved in patients who had achieved a very good partial response (VGPR) or better (41.8 vs 20.7 months, p = 0.0070). As the best response, the rates of partial response or better were 85.5% comprising stringent complete response (sCR, 21.7%), complete response (CR, 10.8%), VGPR (18.1%), and partial response (PR, 34.9%). The most frequently observed grade 3 or higher adverse events during the VMP therapy were anemia (28.9%), neutropenia (15.6%), thrombocytopenia (6.0%), and peripheral neuropathy (2.4%). The most frequently observed grade 3 or higher adverse events during the Rd therapy were anemia (3.5%), neutropenia (1.8%), and skin rush (5.3%). The most frequently observed grade 3 or higher adverse events during lenalidomide maintenance therapy were anemia (7.4%) and neutropenia (24.1%). Thus, VMP induction therapy followed by Rd consolidation and lenalidomide maintenance is considered a well-tolerated and effective regimen in transplant-ineligible NDMM. This trial is registered with UMIN-CTR with the identification number UMIN000009042.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Taxa de Sobrevida
8.
Gan To Kagaku Ryoho ; 46(6): 1043-1047, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273172

RESUMO

Ixazomib, an oral proteasome inhibitor, has been demonstrated to significantly improve progression-free survival(PFS)in patients with relapsed and refractory multiple myeloma(RRMM). Ixazomib has recently been approved in Japan, but its effectiveness and safety have not been fully investigated in a clinical setting. We retrospectively analyzed the records of 28 patients with RRMM who were treated with ixazomib in combination with lenalidomide and dexamethasone(IRd)in our institution between June 2017 and June 2018. The median patient age was 75 years at the start of IRd therapy. In total, 46.4% of the patients had previously received more than 3 treatment lines, prior to this study. The overall response rate was 37.0%, and the median PFS was 286 days. Over a median of 5 cycles of IRd, Grade 3 to 4 leukocytopenia, thrombocytopenia, and anemia occurred in 17.9%, 14.3%, and 32.1% of the patients, respectively; these incidences were higher than in previous reports. The severity of diarrhea or rash, however, was comparable with that in other studies. Patients with an estimated glomerular filtration rate of less than 50mL/min/1.73m2 received a lower cumulative dose of ixazomib and lenalidomide than those with other rates. PFS did not significantly differ between the 2 groups. Although it is necessary to carefully observe IRdtreated patients for hematological toxicity, IRd therapy is effective in heavily pretreated RRMM patients. It might be reasonable to reduce the dose of ixazomib in patients with renal impairment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo , Compostos de Boro , Dexametasona , Glicina/análogos & derivados , Humanos , Japão , Lenalidomida , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
9.
Rinsho Ketsueki ; 58(7): 772-775, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28781273

RESUMO

A 91-year-old male with fever of unknown origin was referred to our department. 18F-FDG PET/CT scan revealed a high FDG uptake in abdominal lymph nodes and multiple bones. The bone marrow biopsy showed fibrosis and atypical megakaryocytes, which were consistent with myelofibrosis. The patient died 28 days after admission and an autopsy was performed. The lymph nodes and bone marrow specimens revealed scattered Reed-Sternberg cells and a dearth of lymphoid cells with fibrosis. A final diagnosis of lymphocyte-depleted classical Hodgkin lymphoma (LDCHL) with bone marrow involvement was made. It is necessary to identify LDCHL during differential diagnosis for bone marrow fibrosis accompanied by lymphadenopathy.


Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/patologia , Idoso de 80 Anos ou mais , Autopsia , Evolução Fatal , Doença de Hodgkin/complicações , Humanos , Masculino , Invasividade Neoplásica , Mielofibrose Primária/etiologia
10.
Rinsho Ketsueki ; 57(7): 839-47, 2016 07.
Artigo em Japonês | MEDLINE | ID: mdl-27498726

RESUMO

The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment. Although statistical analysis showed that treatment with melphalan, bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of hematological malignancies, lenalidomide administration was more frequent in the patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related diseases more accurately, accumulation of a larger number of patients and longer observation are needed.


Assuntos
Mieloma Múltiplo , Segunda Neoplasia Primária , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Adulto Jovem
11.
Rinsho Ketsueki ; 55(1): 105-9, 2014 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-24492027

RESUMO

In order to clarify the usefulness of measuring procalcitonin (PCT) values under the extreme condition called febrile neutropenia (FN), PCT was measured with immunochromatographic assay (ICA) and electro-chemi-luminescence immunoassay (ECLIA) at two time points: upon FN occurrence and 12 to 24 hours after FN occurrence, and correlations and associations between the two methods were reviewed. A strong correlation between the ICA and ECLIA results was observed when Spearman's rank correlation coefficient was 0.878, and the association was also demonstrated by Fisher's direct test since P=4.68×10(-10). Special equipment is not required, the operations are simple, and the ICA method currently adopted by many facilities can be used as the standard method even for the clinical condition known as FN.


Assuntos
Calcitonina/sangue , Cromatografia de Afinidade/métodos , Neutropenia Febril/diagnóstico , Precursores de Proteínas/sangue , Idoso , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Neutropenia Febril/sangue , Feminino , Humanos , Medições Luminescentes/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
J Infect Chemother ; 19(1): 103-11, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22948387

RESUMO

The aim of this study was to evaluate the usefulness of carbapenems as initial treatment for febrile neutropenia (FN), and in patients unresponsive to this initial therapy, to evaluate the efficacy of subsequent treatment with aminoglycosides (AGs) or ciprofloxacin (CPFX). FN patients were randomized to receive cefepime (CFPM, control), panipenem/betamiprom (PAPM/BP), or meropenem (MEPM). Defervescence, an outcome endpoint, was evaluated 3 days later. Patients with minimal response were given CPFX or AGs, and their responses were reevaluated on day 7. A total of 255 patients were included. The efficacies of CFPM, PAPM/BP, and MEPM were comparable. In patients unresponsive to this initial therapy, the efficacy of subsequent CPFX and AGs treatments was also similar. There was no significant between-arm difference in cumulative efficacy on days 14 and 30. Adverse reactions were infrequent and mild. In conclusion, PAPM/BP and MEPM are as useful as CFPM as initial therapy for FN, and AGs are as efficacious as CPFX in patients unresponsive to the initial therapy.


Assuntos
Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Febre/tratamento farmacológico , Doenças Hematológicas/tratamento farmacológico , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Cefepima , Cefalosporinas/uso terapêutico , Feminino , Humanos , Masculino , Meropeném , Estudos Prospectivos , Tienamicinas/uso terapêutico , Resultado do Tratamento , Adulto Jovem
13.
J Infect Chemother ; 19(6): 1126-34, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23813092

RESUMO

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-ß-D-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31% achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7% of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as "not classified" compared with "possible invasive fungal disease" according to the EORTC/MSG criteria. Moreover, six "not classified" patients were positive for either plasma (1-3)-ß-D-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-ß-D-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections.


Assuntos
Antifúngicos/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/microbiologia , Micoses/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Adolescente , Adulto , Idoso , Antibioticoprofilaxia , Antifúngicos/efeitos adversos , Antígenos de Fungos , Neutropenia Febril/etiologia , Feminino , Galactose/análogos & derivados , Humanos , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Micoses/sangue , Micoses/diagnóstico , Micoses/prevenção & controle , Estudos Prospectivos , Pirimidinas/efeitos adversos , Triazóis/efeitos adversos , Voriconazol , Adulto Jovem
14.
Int J Hematol ; 118(5): 609-617, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37668833

RESUMO

To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Bortezomib/uso terapêutico , Quimioterapia de Indução , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
15.
Sci Rep ; 13(1): 5159, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36991096

RESUMO

Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18-9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower ß2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/µL), non-deviated κ/λ ratio (0.1-10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/µL and 1 point for < 1400/µL) and κ/λ ratio (0 points for 0.1-10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.


Assuntos
Mieloma Múltiplo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócitos , Estudos Prospectivos , Microglobulina beta-2/metabolismo
16.
Leuk Res Rep ; 20: 100395, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076634

RESUMO

To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis.

17.
Hematol Rep ; 14(2): 165-171, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35735735

RESUMO

Adult-onset primary autoimmune neutropenia (AIN) is an extremely rare but sometimes life-threatening disease. Its pathophysiology is still to be clarified. We describe a case with adult-onset primary AIN with phagocytosis of mature granulocytes by macrophages in bone marrow. A 77-year-old male was referred to our hospital with severe neutropenia. Based on the normal cellular bone marrow without morphological dysplasia and the positivity of anti-neutrophil antibodies in the serum, adult-onset primary AIN was diagnosed. After five years from the initiation of granulocyte colony-stimulating-factor therapy, neutropenia had progressed. At that time, the second bone marrow examination revealed segmented neutrophils phagocytosed by macrophages. Continuous low dose prednisolone succeeded to increase the neutrophil count. An impressive morphological feature of AIN indicated the destruction of mature granulocytes in bone marrow by antibody-dependent cellular phagocytosis mediated by granulocyte-specific antibodies. More cases should be accumulated to elucidate the precise mechanism and establish the optimal therapy.

18.
Am J Clin Pathol ; 158(5): 604-615, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36018052

RESUMO

OBJECTIVES: Eltrombopag, a thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA). Cytomorphologic changes in bone marrow after eltrombopag administration are still unclear. This study examined the effect of eltrombopag on cytomorphologic findings using data from prior phase 2 studies (E1201 and E1202). METHODS: Microscopic examinations were performed in 31 patients with AA (E1201 [n = 21], E1202 [n = 10]). The relationship between hematologic improvement and morphologic findings was also investigated. RESULTS: In 5 patients (E1201 [n = 3], E1202 [n = 2]), the bone marrow blast count increased after initiation of eltrombopag treatment compared with screening values. The blast count was less than 5%, and the increase in bone marrow blasts was transient in all 4 patients who had bone marrow examinations at follow-up. In 8 patients (E1201 [n = 5], E1202 [n = 3]), dysplastic forms of megakaryocytes were found in the bone marrow following treatment initiation. Dysmegakaryopoiesis of 10% or more was found in 3 patients. None of the patients revealed micromegakaryocytes. Ten patients showed an increase in bone marrow blasts and/or dysmegakaryopoiesis following treatment initiation. Nine of 10 patients showed hematologic improvement in 1 or more lineages. CONCLUSIONS: Dysmegakaryopoiesis without micromegakaryocytes and a transient increase of less than 5% in bone marrow blast count may be signs of hematologic improvement with eltrombopag for patients with AA.


Assuntos
Anemia Aplástica , Humanos , Anemia Aplástica/tratamento farmacológico , Receptores de Trombopoetina , Medula Óssea , Evolução Clonal
19.
Ther Adv Hematol ; 13: 20406207221104584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35785245

RESUMO

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.

20.
Ther Adv Hematol ; 13: 20406207221142487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530751

RESUMO

Background: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. Objectives: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. Design: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. Methods: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. Results: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower ß2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. Conclusion: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/µl; 1 point for <200/µl) or WBC counts (0 points for ⩾3500/µl; 1 point for <3500/µl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.

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