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1.
Int J Cancer ; 152(9): 1884-1893, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2267079

ABSTRACT

Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR performance in elderly patients are available to date. We compared safety and efficacy of BR in patients ≥70 years (elderly) vs <70 years (younger) treated at our institution. Among 201 patients, 113 were elderly (median age: 77 years), including 38 patients ≥80 years, and 88 were younger (median age: 62 years). Elderly patients had more bone marrow involvement by lymphoma, anemia, ECOG status 3 and high-risk disease follicular lymphoma (P < .05 for all). Fifty-four percent of elderly received full dose of bendamustine vs 79.5% of younger patients. More elderly patients (54%) vs younger (43.2%) experienced treatment delay. Less elderly proceeded to rituximab maintenance. Overall, the number of adverse events per patient and transformed B-Cell lymphoma/secondary malignancies were similar between groups. Elderly patients had less febrile neutropenia, rituximab-associated infusion reactions, but more herpes zoster reactivation. There were more deaths in the elderly (37.2%) vs younger (10.2%) groups (P < .001), mainly due to non-lymphoma-related causes. With median follow-up of 42 months [4.0-97.0] disease-free survival for the elderly was similar to younger patients. There was no difference between patients <80 and ≥80 years (P = .274). In conclusion, the real-world elderly patients have more advanced disease and higher ECOG status. BR is well-tolerated; elderly patients had lower incidence of febrile neutropenia. Dose reduction and treatment delays are common, but BR efficacy was not affected even in very old patients (≥80 years).


Subject(s)
Febrile Neutropenia , Lymphoma, Mantle-Cell , Lymphoma, Non-Hodgkin , Humans , Adult , Aged , Middle Aged , Rituximab/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Bendamustine Hydrochloride/adverse effects , Lymphoma, Non-Hodgkin/etiology , Febrile Neutropenia/drug therapy , Febrile Neutropenia/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects
2.
N Engl J Med ; 386(26): 2482-2494, 2022 06 30.
Article in English | MEDLINE | ID: covidwho-1984509

ABSTRACT

BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS: We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS: Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS: Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Mantle-Cell , Adenine/administration & dosage , Adenine/analogs & derivatives , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/adverse effects , Disease Progression , Humans , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/mortality , Maintenance Chemotherapy , Piperidines/administration & dosage , Piperidines/adverse effects , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Remission Induction , Rituximab/administration & dosage , Rituximab/adverse effects , Survival Analysis
3.
Int J Infect Dis ; 121: 85-88, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1873077

ABSTRACT

Although messenger ribonucleic acid vaccines are substantially effective toward SARS-CoV-2 infection, patients with hematologic malignancies are still prone to the virus. Herein, we report a fatal case of breakthrough SARS-CoV-2 Delta variant infection in a patient with mucosa-associated lymphoid tissue lymphoma with remission by bendamustine-rituximab (BR) therapy completed a year ago. The serologic study revealed impaired responsiveness toward vaccines and prolonged high viral load after infection. BR therapy seemingly induced an immune escape. Prevention and treatment strategies for such vulnerable patients should be clarified immediately.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride/adverse effects , Humans , Rituximab/adverse effects
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