RESUMEN
With improving outcomes in amyloid light-chain (AL) amyloidosis, there is a need to study novel agents in this setting. We report outcomes of 40 patients with relapsed AL amyloidosis treated with ixazomib + lenalidomide + dexamethasone (IRd). Haematological responses were assessed on an intention-to-treat basis at three months: complete response (CR) - 8 (20·5%), very good partial response (VGPR) - 8 (20·5%), partial response (PR) - 7 (17·9%) and no response (NR) - 16 (41·0%). One patient had missing data. Six patients subsequently improved response. Best responses were: CR - 10 (25·6%), VGPR - 8 (20·5%), PR - 7 (17·9%), NR - 14 (35·9%). Cardiac and renal organ responses occurred in 5·6% and 13·3% respectively. Median progession-free survival (PFS) was 17·0 months (95% CI 7·3-20·7 months), improving to 28·8 months (95% CI 20·6-37·0 months) in those achieving CR/VGPR. Median overall survival was 29·1 months (95% CI 24-33 months). Serious adverse events were seen in 14 (35·0%) patients inclusive of 15 admissions due to: infection (6/15, 40·0%), fluid overload (5/15, 33·3%), cardiac arrhythmia (2/15, 13·3%), renal dysfunction (1/15, 6·6%) and anaemia (1/15, 6·6%). In summary, IRd is an oral treatment option with a manageable toxicity profile leading to deep responses in 47% of patients with relapsed AL amyloidosis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos de Boro/uso terapéutico , Dexametasona/uso terapéutico , Glicina/análogos & derivados , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Lenalidomida/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Compuestos de Boro/farmacología , Dexametasona/farmacología , Femenino , Glicina/farmacología , Glicina/uso terapéutico , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Lenalidomida/farmacología , Masculino , Persona de Mediana Edad , Recurrencia Local de NeoplasiaRESUMEN
The complement inhibitor, eculizumab, has revolutionised the management of atypical haemolytic uraemic syndrome (aHUS), although the optimum treatment duration is debated. Twenty-two cases of acute aHUS managed with eculizumab were retrospectively reviewed, including outcomes after eculizumab withdrawal. Although 41% had an associated complement genetic abnormality, mutation status did not affect severity of clinical presentation. Sixty-four percent required renal replacement acutely, with a high incidence of nephrotic range proteinuria (47%). Eculizumab followed a median of 6 days of plasma exchange. After a median duration of therapy of 11 weeks (range 1-227), haematological recovery was seen in 100%, while 81% achieved at least partial renal recovery (median increase in estimated glomerular filtration rate (eGFR) 49 ml/min/1·73 m2 ). At median duration of follow-up of 85 weeks (range 4-255), 54·5% had eGFR ≥ 60 ml/min/1·73 m2 , 27% had CKD, 14% were on dialysis, and 4·5% had died. Eculizumab was withdrawn in 59% (13/22) cases following complete haematological and renal recovery. Three of these 13 patients (23%) subsequently relapsed, with defined triggers in 2/3, but all made a full recovery with rapid resumption of eculizumab. There was a significant association between higher presenting creatinine and poorer renal outcomes. A strategy of eculizumab withdrawal in selected cases is both safe and cost effective.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Privación de Tratamiento , Adulto , Inactivadores del Complemento/uso terapéutico , Femenino , Tasa de Filtración Glomerular , Humanos , Pruebas de Función Renal , Masculino , Recuperación de la Función , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Immune thrombotic thrombocytopenic purpura (iTTP) is an acute, multisystem thrombotic microangiopathy mediated by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) autoantibodies. Immunosuppression with anti-CD20 therapy is the mainstay of treatment. MabThera's patent has now expired and biosimilars have been approved. Eighty-four consecutive patient episodes over 2 years, prior to and following our switch to Truxima are presented. Day 1 (D1), Day 28 (D28) and 3-month platelet counts, ADAMTS13 activity, and CD19 levels, adverse reactions and infective complications were recorded. Platelet counts were not significantly different between acute MabThera and Truxima treatment (D1 P = 0.085, D28 P = 0.77, 3 months P = 0.71) and electively (D1 P = 0.79, D28 P = 0.68, 3 months P = 0.99). ADAMTS13 recovery also was not significantly different acutely (D1 P = 0.99, D28 P = 0.27, 3 months P = 0.26) and electively (D1 P = 0.59, D28 P = 0.61, 3 months P = 0.34). CD19% depletion at D1 and 3 months was not significantly different acutely (D1 P = 0.52, 3 months P = 0.56) and electively (D1 P = 0.22, 3 months P = 0.19). Infusion reactions and infective complications were comparable with both therapies. This is the first series of the Rituximab biosimilar Truxima to be reported in iTTP, demonstrating equivalence to MabThera in terms of ADAMTS13 recovery, CD19 depletion, and platelet count at D28 and 3 months post-administration, with comparable infusion and infective complications. The financial benefit of the biosimilar anti-CD20 is considerable.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Rituximab/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Biosimilares Farmacéuticos/farmacología , Femenino , Humanos , Masculino , Púrpura Trombocitopénica Trombótica/patología , Rituximab/farmacologíaRESUMEN
Bortezomib is standard treatment in AL amyloidosis (AL), but is contraindicated in patients with significant neuropathy. Carfilzomib, a second-generation proteosomal inhibitor, results in a lower incidence of neuropathy than bortezomib, but data in AL is scant. We report a cohort of five AL patients treated with upfront carfilzomib. All had cardiac, peripheral and autonomic neuropathy at presentation. All achieved at least a very good partial haematological response. There was no worsening in cardiac function, peripheral or autonomic neuropathy. Carfilzomib is an effective upfront treatment option in AL patients with peripheral and/or autonomic neuropathy (without severe cardiac or renal involvement).
Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/etiología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/etiología , Adulto , Anciano , Antineoplásicos/efectos adversos , Enfermedades del Sistema Nervioso Autónomo/inducido químicamente , Bortezomib/efectos adversos , Estudios de Cohortes , Contraindicaciones de los Medicamentos , Quimioterapia Combinada , Glucocorticoides/uso terapéutico , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Persona de Mediana Edad , Oligopéptidos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Inhibidores de Proteasoma/uso terapéutico , Resultado del TratamientoRESUMEN
Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40-89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment. Of 45 patients with fluorescence in situ hybridization results 64% had adverse risk, 19 patients (22·4%) had an estimated glomerular filtration rate <45 ml/min. Grade ≥3 non-haematological toxicities occurred in 42·4%, and grade ≥3 neutropenia and thrombocytopenia in 38% and 24% respectively, but only 18·8% had dose reductions. The overall response rate was 52·9%. At a median follow-up of 13·2 months, median progression-free survival was 5·2 months [95% confidence interval (CI) 4·150-6·238], and median overall survival was 13·7 months (95% CI 11·775-15·707). No significant difference was seen in response, survival or tolerability by renal function, age or cytogenetic risk. This real-world data support the results seen in published clinical trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Dexametasona/administración & dosificación , Resistencia a Antineoplásicos/genética , Femenino , Variación Genética , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Recurrencia , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/etiología , Retratamiento , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Resultado del TratamientoRESUMEN
Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying a poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients with SCNS-DLBCL treated with R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12·5 mg by intrathecal injection day 1; idarubicin 10 mg/m(2) /day IV days 1 and 2; dexamethasone 100 mg/day IV infusion over 12 h days 1-3; cytosine arabinoside 1000 mg/m(2) /day IV over 1 h days 1 and 2; and methotrexate 2000 mg/m(2) IV over 2 h day 3. Ten out of 23 (44%) patients had CNS involvement at initial presentation ('new disease'), 10/23 (44%) had relapsed disease and 3/23 (13%) had primary refractory disease. 14/23 (61%) of patients responded - 6 (26%) complete response, 8 (35%) partial response. Grade 3-4 haematological toxicity was seen in all cycles, with no grade 3-4 or long-term neurological toxicity. Median follow-up for surviving patients was 49 months. At 2 years, estimated progression-free survival (PFS) was 39% and overall survival (OS) was 52%. Encouraging outcomes were reported in patients with new disease, with 5-year estimated PFS of 50% and OS 75%. R-IDARAM is a well-tolerated regimen with encouraging efficacy in patients with SCNS-DLBCL, although patients with relapsed or refractory disease continue to fare poorly.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/administración & dosificación , Infusiones Intravenosas , Inyecciones Espinales , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab/administración & dosificación , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/terapia , Terapia Recuperativa , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Cisplatino/uso terapéutico , Citarabina/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Supervivencia sin Progresión , Talidomida/uso terapéutico , Trasplante Autólogo , Adulto JovenAsunto(s)
Bases de Datos Factuales , Cardiopatías , Hipertensión , Modelos Cardiovasculares , Mieloma Múltiple , Oligopéptidos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Cardiopatías/inducido químicamente , Cardiopatías/mortalidad , Cardiopatías/prevención & control , Humanos , Hipertensión/inducido químicamente , Hipertensión/mortalidad , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Guías de Práctica Clínica como Asunto , Estudios RetrospectivosRESUMEN
High dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) remains the standard consolidation in transplant eligible multiple myeloma (MM) patients. The timing between HDM administration and hematopoietic stem cell return (HSCR) varies among institutions, with a 'rest period' of 48 hours (h) employed by some for patients with renal impairment (RI). We investigated the differences in hematopoietic recovery and HDM toxicity between MM patients with RI who had HSCR after 24 vs 48 h from HDM. Fifty MM patients with RI (48 h group; n = 31 and 24 h group; n = 19) were included. No statistically significant differences were noted in surrogates for hematopoietic recovery and HDM toxicity between both groups. Only one death occurred in the 24 h group. No patients required renal replacement therapy. Therefore, a 24 h period between HDM and AHSC infusion appears safe for MM patients with RI.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Melfalán , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante AutólogoAsunto(s)
Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Humanos , Mieloma Múltiple/mortalidad , Recurrencia , Retratamiento , Resultado del TratamientoRESUMEN
Background: Daratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use.Method: Patients treated with daratumumab monotherapy (2016-2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre.Results: Of 50 evaluable patients, haematological responses at 3 months were: CR - 19 (38%), VGPR - 14 (28%), PR - 9 (18%) and no response - 8 (16%). Median time to response was 1 (1-6) month. Of assessable patients, cardiac, renal and hepatic responses were seen in 43.8%, 25.0% and 0% of patients whilst progression occurred in 25.0%, 12.5% and 37.5% respectively. Patients achieving a CR had longer median OS (not reached vs. 22.7 months [95% CI 17.0-28.4 months]) (p = .036). Furthermore, patients achieving a rapid response (at 1 month) had a longer median PFS (not reached vs. 9 months [95% CI 5.8-12.2 months]) (p = .013).Conclusion: Daratumumab monotherapy is effective in multiply-relapsed systemic AL amyloidosis and should be considered, if available, in patients who have not received prior daratumumab therapy. Responses are achieved rapidly and overall response rate was 84%. CR predicts overall survival whilst speed of response is predictive of a longer PFS.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Células Plasmáticas/metabolismo , ADP-Ribosil Ciclasa 1/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/epidemiología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Masculino , Persona de Mediana Edad , Células Plasmáticas/patología , Supervivencia sin Progresión , Resultado del TratamientoAsunto(s)
Mieloma Múltiple , Inhibidores de Proteasoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos de Boro , Dexametasona/uso terapéutico , Glicina/análogos & derivados , Humanos , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de Proteasoma/uso terapéuticoRESUMEN
Since 2005, University College London Hospital (UCLH) has operated a hotel-based Ambulatory Care Unit (ACU) for hematology and oncology patients requiring intensive chemotherapy regimens and hematopoietic stem cell transplants. Between January 2005 and 2011 there were 1443 patient episodes, totaling 9126 patient days, with increasing use over the 6-year period. These were predominantly for hematological malignancy (82%) and sarcoma (17%). Median length of stay was 5 days (range 1-42), varying according to treatment. Clinical review and treatment was provided in the ACU, with patients staying in a local hotel at the hospital's expense. Admission to the inpatient ward was arranged as required, and there was close liaison with the inpatient team to preempt emergency admissions. Of the 523 unscheduled admissions, 87% occurred during working hours. An ACU/hotel-based treatment model can be safely used for a wide variety of cancers and treatments, expanding hospital treatment capacity, and freeing up inpatient beds for those patients requiring them.