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Background: Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods: We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B-cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high-dose methotrexate (HD-MTX) containing chemotherapy regimens: MPV/Ara-C (HD-MTX, procarbazine, and vincristine, followed by cytarabine [Ara-C]) (n = 94, 50%), MATRix (HD-MTX, Ara-C, thiotepa, and rituximab) (n = 19, 10%), HD-MTX/Ara-C (n = 31, 16%), HD-MTX monotherapy (n = 35, 18%) and MBVP (HD-MTX, carmustine, teniposide, prednisolone) (n = 11, 6%). Results: Cumulative median HD-MTX and Ara-C doses were 17 g/m2 (range: 1-64 g/m2) and 12 g/m2 (0-32 g/m2) respectively. Using 14 g/m2 as the reference dose, the median HD-MTX relative dose intensity (HD-MTX-RDI) was 1.25 (0.27-4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD-MTX. At a median follow-up of 3.41 years (0.06-9.42), progression-free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara-C cohort (2-year PFS 74%, 2-year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara-C administration and HD-MTX-RDI > 0.75 were associated with longer PFS and OS. Conclusion: Sequential, response-adapted approaches can improve outcomes, even in older patients who are ineligible for a high-intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.
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Population-based studies have demonstrated a high risk of second cancers, especially of the skin, among patients with chronic lymphocytic leukaemia (CLL). We describe age-standardised incidence ratios (SIRs) of second primary malignancies (SPM) in Australian patients with relapsed/refractory CLL treated with at least two lines of therapy, including ibrutinib. From December 2014 to November 2017, 156 patients were identified from 13 sites enrolled in the Australasian Lymphoma and Related Diseases Registry, and 111 had follow-up data on rates of SPM. At 38.4 months from ibrutinib therapy commencement, 25% experienced any SPM. SIR for melanoma and all cancers (excluding nonmelanomatous skin cancers) were 15.8 (95% confidence interval (CI): 7.0-35.3) and 4.6 (95% CI: 3.1-6.9) respectively. These data highlight the importance of primary preventive interventions and surveillance, particularly as survival from CLL continues to improve.
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Leucemia Linfocítica Crónica de Células B , Neoplasias Primarias Secundarias , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenina/análogos & derivados , Adenina/uso terapéutico , Pueblos de Australasia , Australia/epidemiología , Incidencia , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Neoplasias Primarias Secundarias/epidemiología , Piperidinas/uso terapéutico , Pirazoles/uso terapéutico , Sistema de RegistrosRESUMEN
Asciminib is a novel allosteric STAMP (specifically targets the ABL myristoyl pocket) inhibitor of the BCR::ABL1 oncogene. Real-world clinical outcomes of patients with tyrosine kinase inhibitor (TKI)-resistant/intolerant chronic myeloid leukaemia (CML) in Australia on the Managed Access Programme for asciminib showed higher molecular responses for those with intolerance versus resistance ± intolerance to their last TKI. There remains a clinical need to improve outcomes in patients with CML who have resistance to multiple TKIs, especially in the ponatinib-pretreated cohort.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Inhibidores de Proteínas Quinasas , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Australia , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Femenino , Resultado del Tratamiento , Anciano , Adulto , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Piridazinas/uso terapéutico , Anciano de 80 o más Años , Niacinamida/análogos & derivados , PirazolesRESUMEN
Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR-DLBCL have not been replicated in routine care cohorts, as RR-DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR-DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression-free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real-world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.
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Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Patients can often receive sequential treatments, yet these typically yield diminishing periods of disease control, raising questions about optimal therapy sequencing. Novel agents, such as chimeric antigen receptor T-cell therapies and bispecific antibodies, show promise in relapsed MCL, but are often reserved for later treatment lines, which may underserve patients with aggressive disease phenotypes who die early in the treatment journey. To assess the problem of patient attrition from lymphoma-related death limiting sequential treatment, we performed a multicentre retrospective cohort analysis of 389 patients treated at Australian and UK centres over a 10-year period. Deaths from MCL increased after each treatment line, with 7%, 23% and 26% of patients dying from uncontrolled MCL after first, second and third lines respectively. Patients with older age at diagnosis and early relapse after induction therapy were at particular risk of death after second-line treatment. This limitation of sequential treatment by lymphoma-related death provides support for the trial of novel therapies in earlier treatment lines, particularly in high-risk patient populations.
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Linfoma de Células del Manto , Adulto , Humanos , Australia , Linfoma de Células del Manto/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Reino UnidoRESUMEN
Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in Australia and New Zealand (ANZ). Considerable changes to diagnostic and management algorithms have occurred within the last decade. The availability of next-generation sequencing and measurable residual disease assessment by flow cytometry allow for advanced prognostication and response assessments. Novel therapies, including inhibitors of Bruton's tyrosine kinase (BTKi) and B-cell lymphoma 2 (BCL2) inhibitors, have transformed the treatment landscape for both treatment-naïve and relapsed/refractory disease, particularly for patients with high-risk genetic aberrations. Recommendations regarding appropriate supportive management continue to evolve, and special considerations are required for patients with CLL with respect to the global SARS-CoV-2 pandemic. The unique funding and treatment environments in Australasia highlight the need for specific local guidance with respect to the investigation and management of CLL. This consensus practice statement was developed by a broadly representative group of ANZ experts in CLL with endorsement by peak haematology bodies, with a view to providing this standardised guidance.
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COVID-19 , Neoplasias Hematológicas , Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/terapia , Consenso , SARS-CoV-2RESUMEN
Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between 'lowgrade' (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups; G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of the G3BFL cases. With a median of 5 years follow-up, the overall survival and progression-free survival of G3BFL patients was better than that of DLBCL patients (P<0.001 and P<0.001, respectively); however, G3BFL patients were younger (P<0.001) with better performance status (P<0.001), less extranodal disease (P<0.001) and more frequently had normal lactate dehydrogenase (P<0.001) at baseline. The overall and progression-free survival of patients with G3BFL and G3AFL were similar (P=0.83 and P=0.80, respectively). After frontline immunochemotherapy, 24% of G3BFL relapsed; relapse rates were 63% in the DLBCL cohort and 19% in the low-grade FL cohort. Eight percent of relapses occurred beyond 5 years. In this G3BFL cohort, the revised International Prognostic Index successfully delineated risk groups, but the Follicular Lymphoma International Prognostic Index did not. We conclude that patients with immunochemotherapy-treated G3BFL have similar survival outcomes to those with G3AFL, yet a favorable baseline profile and distinctly superior prognosis compared to patients with DLBCL.
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Linfoma Folicular , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Estudios Prospectivos , Recurrencia Local de Neoplasia , Linfoma no Hodgkin/patología , Pronóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológicoRESUMEN
Comprehensive clinical characteristics of Australian patients with classical Hodgkin Lymphoma (cHL) have not previously been systematically collected and described. We report real-world data of 498 eligible patients from the first 5 years of the Lymphoma and Related Diseases Registry (LaRDR), including baseline characteristics, histologic subtype, and treatment patterns in first-line therapy. Patient demographics and distribution of histopathological subtypes of cHL are similar to reported international cohorts. Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was the most common therapy for both early and advanced-stage disease, and 48% of patients with the early-stage disease received radiotherapy. Treatment patterns are consistent with international guidelines. In comorbid patients ≥60 years of age with advanced-stage disease, there is greater variation in treatment. In patients with a recorded response, the objective response rate (ORR) was 96% in early-stage disease, and 88% in advanced-stage disease. Early progression-free survival data suggest Australian patients with cHL have good outcomes, similar to other international studies.
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Enfermedad de Hodgkin , Humanos , Bleomicina/uso terapéutico , Doxorrubicina/uso terapéutico , Vinblastina/uso terapéutico , Dacarbazina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Australia , Sistema de Registros , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Splenectomy is an effective intervention in primary immune thrombocytopenia (ITP). Attempts to define pre-clinical predictors of platelet response to splenectomy are inconsistent. Based on international studies defining the likelihood of platelet response using platelet sequestration, patients with relapsed/refractory ITP being considered for splenectomy at a regional Australian hospital were assessed with 111 indium-labelled autologous platelet sequestration (ILAPS) studies. AIMS: To audit the use of ILAPS in an Australian setting and define its role in predicting response to splenectomy. METHODS: A retrospective review of all patients referred for an ILAPS study at a regional hospital was performed. Results for each patient were expressed as an 'R' value (spleen/ liver uptake ratio) to quantify the platelet sequestration pattern and outcome post-splenectomy, based on platelet counts. RESULTS: A total of 45 patients was identified: 13 underwent splenectomy and 32 were medically managed. Patients with favourable ILAPS scans (pure or predominant splenic sequestration) demonstrated a superior response post-splenectomy (100% overall response rate (ORR); 83.5% complete remission (CR)) compared with those with unfavourable ILAPS scans (mixed or pure hepatic sequestration) (71.4% ORR; 57.1% CR) over 12 months. CONCLUSIONS: The use of ILAPS in the Australian setting is feasible and this experience confirms larger international studies demonstrating its utility as a predictor of response to splenectomy in ITP. An unfavourable ILAPS scan could be considered a negative predictor of response prompting consideration for other emerging ITP treatments such as thrombopoietin-receptor agonists or B-cell depleting therapy such as Rituximab.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Australia/epidemiología , Humanos , Indio , Púrpura Trombocitopénica Idiopática/cirugía , Estudios Retrospectivos , Esplenectomía , Trombocitopenia/cirugía , Resultado del TratamientoRESUMEN
The management of Hodgkin lymphoma (HL) has undergone significant changes in recent years. Due to the predilection of HL to affect younger patients, balancing cure and treatment-related morbidity is a constant source of concern for physicians and patients alike. Positron emission tomography adapted therapy has been developed for both early and advanced stage HL to try and improve the outcome of treatment, while minimising toxicities. The aim of this review is to digest the plethora of studies recently conducted and provide some clear, evidence-based practice statements to simplify the management of HL.
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Enfermedad de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Consenso , Supervivencia sin Enfermedad , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Humanos , Tomografía de Emisión de Positrones/métodos , PronósticoRESUMEN
The role of cytarabine-based induction and autologous stem cell transplantation (ASCT) in front-line treatment of younger patients with mantle cell lymphoma (MCL) is well established, however the utility of intensive approaches in older patients remains unclear. This retrospective study compared first line treatment outcomes in patients aged 60 years or more, treated at six tertiary centres between 2000-2015. 70 patients included had a median age of 69 (60-91) and most (94%) demonstrated advanced stage disease. Treatment regimens included: R-CHOP-like (n = 39), alternating R-CHOP/R-DHAC (n = 10), R-HyperCVAD/R-MA (n = 7), R-CHOP/Cytarabine (Nordic Protocol) (n = 10) and other (n = 4). 16 patients underwent an ASCT. The median follow-up for surviving patients was 37 months. Compared to R-CHOP-like therapies, cytarabine-based regimens were associated with an improved overall response rate (ORR) of 70% vs 33% (p < 0.001) and overall survival (OS) (HR 0.541, [0.292-1.001], p = 0.05). No difference in efficacy between different cytarabine-based regimens was detected, but R-HyperCVAD/R-MA was associated with increased hospitalisation and transfusion requirements. Patients undergoing ASCT demonstrated an improved median OS (HR 0.108 [0.015-0.796], p = 0.029) but were significantly younger. These results reaffirm the use of cytarabine in MCL for selected patients aged over 60. Such regimens should be strongly considered for this population in frontline therapy.
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Citarabina/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Citarabina/metabolismo , Supervivencia sin Enfermedad , Quimioterapia/métodos , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunoterapia/métodos , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Trasplante AutólogoRESUMEN
Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant-eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant-eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression-free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis-PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)-conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1-3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5-2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant-eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.
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Trasplante de Células Madre Hematopoyéticas/métodos , Inmunoterapia/métodos , Quimioterapia de Inducción/métodos , Linfoma de Células del Manto/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina/uso terapéutico , Citarabina/uso terapéutico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Etopósido/uso terapéutico , Femenino , Humanos , Cooperación Internacional , Linfoma de Células del Manto/mortalidad , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inducción de Remisión , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P = .022) and dyslipidemia (P = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.
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Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pirimidinas/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Australia , Dislipidemias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/efectos adversos , Estudios Retrospectivos , Retirada de Medicamento por Seguridad , Enfermedades Vasculares/inducido químicamenteAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Bortezomib/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.
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Antineoplásicos Alquilantes/uso terapéutico , Busulfano/uso terapéutico , Resistencia a Antineoplásicos , Tolerancia a Medicamentos , Hidroxiurea/uso terapéutico , Trastornos Mieloproliferativos/tratamiento farmacológico , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Masculino , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/mortalidad , Neoplasias Primarias Secundarias/etiología , Cromosoma Filadelfia , Retratamiento , Análisis de Supervivencia , Trombosis/etiología , Resultado del TratamientoRESUMEN
Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.
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Certain patients with antibody-mediated autoimmune disease exhibit poor responses to conventional immunosuppression, including B-cell depletion with rituximab. Proteasome inhibitors such as bortezomib demonstrate pleiotropic immunomodulatory effects, including direct toxicity to antibody-producing cells. Here, we report preliminary evidence for the efficacy of bortezomib as salvage therapy for refractory autoimmune hematological disease. Thirteen treatment episodes in 10 patients with autoimmune hematological phenomena (autoimmune hemolytic anemia [AIHA; n = 8], acquired hemophilia (n = 1), immune thrombocytopenia (n = 1), and thrombotic thrombocytopenic purpura [TTP; n = 3]) and a median of 5 (range, 3-12) prior lines of therapy demonstrated an overall response rate of 77% (10 of 13) including 38% (5 of 13) complete remissions. The majority of clinical improvements were rapid, correlated with biomarkers of autoantibody reduction, and were associated with an acceptable safety profile. Responses appeared durable following treatment of TTP and acquired hemophilia; AIHA responses were more limited with a pattern of relapse following bortezomib cessation. These data provide proof of concept for the utility of proteasome inhibition as antibody depletion therapy in autoimmune disease.