ABSTRACT
OBJECTIVE: The clinical benefit of pharmaceutical cares in improving the quality-of-care outcomes is well demonstrated. Clinical pharmacy services are not systematically deployed in cancer units in the absence of economic data. The aim of this prospective, observational 1-year study was to evaluate the clinical, economic and organisational impacts of pharmaceutical care into a multidisciplinary day hospital for patients treated with oral cancer drugs. METHODS: All pharmacists' interventions (PI) were documented and their impact and the probability of adverse drug events were assessed using the clinical, economic and organisational tool. RESULTS: Among 360 admissions, an average of 1.81 PI per admission was accepted. Among 452 PI leading to a clinical benefit on the patient, 16.9% had a major impact, and 1.9% had an impact on survival. The large majority of PIs (87%) increased the quality-of-care organisation. The budget impact model showed a total cost savings and cost avoidance of 539,047 per year and a cost-benefit ratio of 7.07:1. The direct cost-benefit was 201,741, and the cost avoidance was 337,306. CONCLUSION: Multidisciplinary care and pharmaceutical care are key elements to improve cancer patients' outcomes and avoid evitable healthcare costs.
Subject(s)
Antineoplastic Agents , Hematology , Neoplasms , Pharmacy Service, Hospital , Humans , Pharmacists , Prospective Studies , Neoplasms/drug therapy , Cost-Benefit Analysis , Antineoplastic Agents/adverse effects , Pharmaceutical PreparationsSubject(s)
ADP-ribosyl Cyclase 1/antagonists & inhibitors , Antineoplastic Agents, Immunological/therapeutic use , BNT162 Vaccine/therapeutic use , COVID-19/prevention & control , Multiple Myeloma/drug therapy , SARS-CoV-2/immunology , ADP-ribosyl Cyclase 1/immunology , Adult , Aged , Antineoplastic Agents, Immunological/pharmacology , BNT162 Vaccine/pharmacology , COVID-19/complications , COVID-19/immunology , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunogenicity, Vaccine , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/immunology , Prospective StudiesABSTRACT
There is no standard of care in elderly classical Hodgkin lymphoma (cHL) patients. ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), the standard chemotherapy for younger patients, is also used in elderly patients but little is known about toxicity and efficacy. We retrospectively analysed 147 patients aged 60 years and over treated with ABVD in three French haematological centres. Treatment regimen modification was applied in 56 patients for toxicity or HL progression. Bleomycin was removed or reduced in 53 patients, mainly for pulmonary toxicity. Neither initial characteristics nor treatment characteristics were found to correlate with lung toxicity. One hundred and seventeen patients achieved a complete remission, 6 a partial remission, 16 had refractory disease and 8 were non-evaluable. Five-year overall survival was estimated at 67%. With a median follow-up of 58 months, 51 patients died and 14% of deaths were related to lung toxicity. Our study confirms the efficacy of ABVD in elderly patients even if results are inferior to those obtained in younger patients with the same regimen. ABVD can be proposed as front-line chemotherapy in selected elderly cHL patients. The frequency of pulmonary events leads us to propose to either reduce the dose of bleomycin or to remove it from the regimen.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/mortality , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Bleomycin/adverse effects , Bleomycin/therapeutic use , Cause of Death , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Female , Hodgkin Disease/complications , Hodgkin Disease/pathology , Humans , Lung Injury/etiology , Male , Middle Aged , Neoplasm Staging , Prognosis , Vinblastine/adverse effects , Vinblastine/therapeutic useSubject(s)
Leukemia, Large Granular Lymphocytic/diagnosis , Lymphoma, T-Cell/diagnosis , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Biopsy , Bone Marrow , Cell Transformation, Neoplastic , Disease Progression , Disease Susceptibility , Fatal Outcome , Female , Gene Rearrangement , Humans , Immunohistochemistry , Immunophenotyping , Karyotype , Leukemia, Large Granular Lymphocytic/drug therapy , Leukemia, Large Granular Lymphocytic/etiology , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/etiology , Middle Aged , Positron Emission Tomography Computed TomographySubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/drug therapy , Lymphoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/mortality , Consolidation Chemotherapy , Cytarabine/administration & dosage , Etoposide/administration & dosage , Humans , Lymphoma/diagnosis , Lymphoma/mortality , Remission Induction , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Patients with hematological malignancies are at greater risk of severe COVID-19 and have been prioritized for COVID-19 vaccination. A significant proportion of them have an impaired vaccine response, both due to the underlying disease and to the treatments. METHODS: We conducted a prospective observational study to identify the specific risks of the outpatient population with hematological diseases. RESULT: Between 22 December 2021 to 12 February 2022, we followed 338 patients of which 16.9% (n = 57) developed SARS-CoV-2 infection despite previous vaccination (94.7%). COVID-19 patients were more likely to have received immunotherapy (85.5% vs. 41%, p < 10-4), and particularly anti-CD20 monoclonal antibodies (40% vs. 14.9%, p < 10-4) and Bruton's tyrosine kinase inhibitors (BTKi) (7.3% vs. 0.7%, p < 10-2). There was no significant difference in demographic characteristics or hematological malignancies between COVID-19-positive and non-positive patients. Patients hospitalized for COVID-19 had more frequently received immunotherapy than patients with asymptomatic or benign forms (100% vs. 77.3%, p < 0.05). Hospitalized COVID-19 patients had a higher proportion of negative or weakly positive serologies than non-hospitalized patients (92.3% vs. 61%, p < 0.05). Patients who received tixagevimab/cilgavimab prophylaxis (n = 102) were less likely to be COVID-19-positive (4.9 vs. 22%, p < 0.05) without significant difference in hospitalization rates. CONCLUSION: In the immunocompromised population of patients with hematological malignancies, the underlying treatment of blood cancer by immunotherapy appears to be a risk factor for SARS-CoV-2 infection and for developing a severe form.
Subject(s)
COVID-19 , Hematologic Neoplasms , Humans , COVID-19/therapy , SARS-CoV-2 , COVID-19 Vaccines , T-Lymphocytes , Hematologic Neoplasms/therapy , Hematologic Neoplasms/drug therapy , VaccinationABSTRACT
Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin-bleomycin-vinblastine-dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide-etoposide-oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m(2) days 1-3), etoposide (150 mg/m(2) days 1-3) and oxaliplatin (130 mg/m(2) day 1). Patients <65 years old received high-dose therapy followed by autologous stem-cell transplantation (HDT-ASCT). Response was assessed by computed and positron-emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose-reductions. Twenty-six patients underwent HDT-ASCT. With median follow-up at 5 years, the 5-year overall and event-free survival rates were 74% and 63%, respectively. IVOx is a well-tolerated outpatient regimen for relapsed HL, that does not hamper stem-cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Etoposide/administration & dosage , Hodgkin Disease/mortality , Hodgkin Disease/prevention & control , Ifosfamide/administration & dosage , Organoplatinum Compounds/administration & dosage , Stem Cell Transplantation , Adolescent , Adult , Aged , Bleomycin/administration & dosage , Dacarbazine/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Oxaliplatin , Prospective Studies , Recurrence , Survival Rate , Transplantation, Autologous , Vinblastine/administration & dosageABSTRACT
Although anti-CD38 monoclonal antibodies have improved the prognosis of relapsed/refractory multiple myeloma (RRMM), some patients still experience early relapses with poor outcomes. This present study evaluated the predictive value of FDG PET/CT parameters for RRMM prior to initiating anti-CD38 treatment. We included 38 consecutive RRMM patients who underwent a PET/CT scan treated at our institution at relapse. The median PFS was 12.5 months and the median OS was not reached. 42% of the patients had an initial ISS score of 1, 37% of 2, and 21% of 3. The presence of >3 focal lesions (FLs, n = 19) and the ISS score were associated with inferior PFS (p = 0.0036 and p = 0.0026) and OS (p = 0.025 and p = 0.0098). Patients with >3 FLs had a higher initial ISS score (p = 0.028). In multivariable analysis, the ISS score and >3 FLs were independent prognostic factors for PFS (p = 0.010 and p = 0.025 respectively), and combined they individualized a high-risk group with a median PFS and OS of 3.1 months and 8.5 months respectively vs. not reached for the other patients. The presence of >3 FLs on PET was predictive of survival outcomes in patients with RRMM treated using CD38 targeted therapy. Combined with the initial ISS, an ultra-high-risk RRMM population can thus be identified.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/diagnosis , Hodgkin Disease/drug therapy , Positron-Emission Tomography , Bleomycin/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Etoposide/therapeutic use , Humans , Neoplasm Staging , Prednisone/therapeutic use , Procarbazine/therapeutic use , Treatment Outcome , Vincristine/therapeutic useSubject(s)
Doxorubicin/analogs & derivatives , Hodgkin Disease/drug therapy , Adolescent , Adult , Doxorubicin/therapeutic use , Female , Hodgkin Disease/pathology , Hodgkin Disease/surgery , Humans , Male , Middle Aged , Neoplasm Staging , Polyethylene Glycols/therapeutic use , Recurrence , Retrospective Studies , Stem Cell Transplantation , Young AdultABSTRACT
Primary central nervous system lymphoma (PCNSL) is a rare topographic variant of diffuse large B-cell lymphoma (DLBCL). While prognostic scales are useful in clinical trials, no dynamic prognostic marker is available in this disease. We report here the prognostic value of early metabolic response by 18F-FDG PET scanner (PET) in 25 newly diagnosed immunocompetent PCNSL patients. Induction treatment consisted of four cycles of Rituximab, Methotrexate and Temozolamide (RMT). Based on patient's general condition, consolidation by high-dose Etoposide and Aracytine was given to responding patients. Brain MRI and PET were performed at diagnosis, after two and four cycles of RMT, and after treatment completion. Two-year progression-free (PFS) and overall survival (OS) were 62% and 74%, respectively for the whole cohort. Best responses after RMT induction were 18 (72%) complete response (CR)/CR undetermined (CRu), 4 (16%) partial response, 1 (4%) progressive disease and 2 (8%) stable disease. Response evaluation was concordant between MRI and PET at the end of induction therapy. Nineteen patients (76%) had a negative PET2. Predictive positive and negative values of PET2 on end-of-treatment (ETR) CR were 66.67% and 94.74%, respectively. We observed a significant association between PET2 negativity and ETR (p = 0.001) and longer PFS (p = 0.02), while having no impact on OS (p = 0.32). Two years PFS was 72% and 33% for PET2- and PET2+ patients, respectively (p < 0.02). PET2 evaluation may help to early define a subgroup of CR PCNSL patients with a favorable outcome.
ABSTRACT
Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease.
Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/mortality , Combined Modality Therapy/methods , Female , France , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Analysis , Treatment OutcomeSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Clonal Hematopoiesis/drug effects , Leukemia, Myeloid, Acute/drug therapy , Neoplastic Stem Cells/drug effects , Sulfonamides/therapeutic use , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Humans , Leukemia, Myeloid, Acute/pathology , Neoplastic Stem Cells/pathology , Remission Induction , Sulfonamides/adverse effects , Treatment OutcomeSubject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Blood Transfusion/ethics , Hematinics/administration & dosage , Jehovah's Witnesses , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prednisone/administration & dosage , Prednisone/adverse effects , Treatment Outcome , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
BACKGROUND: Salvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. PATIENTS AND METHODS: We substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX. RESULTS: Grade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT. CONCLUSION: R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.
Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Cytarabine/therapeutic use , Dexamethasone/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Organoplatinum Compounds/therapeutic use , Salvage Therapy/methods , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/adverse effects , Cytarabine/adverse effects , Dexamethasone/adverse effects , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Lymphoma, B-Cell/mortality , Lymphoma, B-Cell/pathology , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Oxaliplatin , Recurrence , Retrospective Studies , Rituximab , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Farnesyltransferase (Ftase) was identified by gene-expression profiling and by preclinical evaluation in in vitro and in vivo mantle cell lymphoma (MCL) models as a rational therapeutic target in MCL, one of the most refractory B-cell lymphomas. We conducted a multicenter phase II study of a potent Ftase inhibitor, tipifarnib, in patients with relapsed or refractory MCL. METHODS: Tipifarnib was administered at 300 mg orally twice daily for the first 21 days of each 28-day cycle for 4 cycles, and in case of response for 6 cycles. Study endpoints were objective response at 4 and 6 cycles, progression free survival (PFS), overall survival, and toxicity. Prediction of response was retrospectively evaluated in the initial tumor biopsy by the RASGRP1/APTX gene expression ratio, and the AKAP13 expression level. RESULTS: Eleven patients (median age, 71 years) were enrolled. Patients received a median number of three prior therapies (range 1-11). Nine patients completed at least 3 cycles of tipifarnib. No grade III-IV hematological toxicities were recorded. One patient presented a complete response (CR) after 4 and a persistent CR at 6 cycles (ORR = 9%). Median PFS was 3 months (range 0.7-14.2). The RASGRP1/APTX gene expression ratio was higher in the responder (n = 1) while the AKAP13 expression was higher in the non-responders (n = 2). This corresponds to the expected result for predicting response to tipifarnib. CONCLUSION: Treatment with tipifarnib relapsed or refractory MCL is associated with low response rates. Limited gene expression studies suggest that response may be associated with molecular targets.