RESUMO
A 72-year-old man with leukocytosis, anemia, and lymphadenopathy was diagnosed with chronic lymphocytic leukemia (CLL) in August 2017 and was carefully monitored in a "watch-and-wait" manner until it became an "active disease." Ibrutinib (IBR) was initiated orally in July 2018 at a dose of 420 mg/day after disease progression due to chromosome 17p deletion (del 17p). The patient showed partial response after transient lymphocytosis while on IBR treatment. IBR induces paronychia and skin disorder due to the disruption of disulfide bonds between cysteine and inhibition of epidermal growth factor receptor due to the off-target effect. This results in reduced quality of life. In February 2019, paronychia (grade 1) developed in the patient's right foot's first toe; hence, topical gentamicin and taping therapy were performed. However, the symptoms persisted without any improvements. In July 2019, paronychia/granulation (grade 2) was aggravated and successfully treated with silver nitrate chemical cauterization and taping therapy. The patient was continuously treated with 420 mg/day IBR without dose reduction or discontinuation, resulting in successful disease control of CLL with del 17p.
Assuntos
Adenina/análogos & derivados , Leucemia Linfocítica Crônica de Células B , Paroniquia , Piperidinas/uso terapêutico , Adenina/uso terapêutico , Idoso , Cauterização , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Inibidores de Proteínas Quinases , Qualidade de Vida , Nitrato de PrataRESUMO
Ponatinib (PON) is a key drug for patients with second tyrosine kinase inhibitor (TKI)-resistant/intolerant Philadelphia chromosome-positive leukemia (Ph+ leukemia); however, the occurrence of vascular adverse events (VAEs) in patients treated with PON should be carefully monitored. A retrospective analysis involving seven patients treated with PON was conducted to elucidate the incidence rate and risk factor for the development of VAEs. In the present study, risk assessment and monitoring of VAEs were performed using SCORE Risk Chart and Suita Score (10-year risk for fatal cardiovascular event), respectively. Despite the prophylactic use of aspirin, cerebral infarction and unstable angina occurred in two patients. By contrast, deep vein thrombosis did not improve in a patient treated with edoxaban. Our data suggest that patients with Ph+ leukemia possessing risk factors, medical history of lifestyle diseases, and administration of long-term second TKI treatment require careful monitoring of VAEs and therapeutic intervention to lifestyle diseases.
Assuntos
Antineoplásicos/efeitos adversos , Imidazóis/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Piridazinas/efeitos adversos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia , Estudos RetrospectivosAssuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citomegalovirus , Mieloma Múltiplo/tratamento farmacológico , Ativação Viral , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/virologia , Ativação Viral/efeitos dos fármacosAssuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Piridazinas , Idoso , Idoso Fragilizado , Humanos , Imidazóis , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/uso terapêutico , Piridazinas/uso terapêutico , Esteroides/uso terapêuticoRESUMO
BACKGROUND: The outcomes of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) can improve with allogeneic hematopoietic stem cell transplantation (HSCT) during the first complete remission after treatment with a tyrosine kinase inhibitor (TKI) combined with chemotherapy. However, frail patients who are not eligible for allogeneic HSCT or those with TKI-resistant mutations within the BCR-ABL kinase domain have a poor clinical course. Blinatumomab (BLIN) is a bispecific T-cell engager antibody construct that directs cytotoxic T cells to CD19-expressing B-ALL cells. To date, only a few studies have shown the safety and efficacy of Blinatumomab (BLIN) + TKI combination therapy for relapsed/refractory (R/R) Ph+ ALL. Here we report the case of two patients with R/R Ph+ ALL who were treated with BLIN + TKI with durable molecular response. CASE PRESENTATION: Patient 1: A 69-year-old Japanese male with R/R Ph+ ALL was treated with conventional chemotherapy and dasatinib in April 2016. In May 2018, he developed molecular relapse due to the acquisition of T315I during dasatinib maintenance therapy. Thereafter, he achieved molecular complete remission (mCR) after switching from dasatinib to ponatinib. However, he developed a second relapse after the emergence of triple compound mutations (G250E/D276G/T315I) in November 2018. He subsequently received a total of nine cycles of BLIN and ponatinib combination therapy, which resulted in sustained mCR without any adverse events. Patient 2: A 69-year-old Japanese female with R/R Ph+ ALL was treated with chemotherapy and imatinib in April 2008. She developed molecular relapse due to the emergence of the T315I mutation in October 2017. She achieved mCR after switching from imatinib to ponatinib. However, she developed a second relapse after acquiring ABL exon4 skipping in addition to T315I. She subsequently received a total of seven cycles of BLIN and ponatinib combination therapy, which resulted in sustained mCR. CONCLUSION: In our two cases, BLIN + ponatinib combination therapy was highly effective for R/R Ph+ ALL without any incidence of severe adverse events. Further studies with larger cohorts are warranted to validate the safety and efficacy of this potent combination therapy.