Rituximab Treatment for Autoinmune Hemolitic Diseases,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3168-3168
Author(s):  
Natalia Schutz ◽  
Jorge Arbelbide ◽  
Walter Skordo ◽  
Susana Viñuales ◽  
Elsa Nucifora ◽  
...  
Keyword(s):  
Partial Response ◽  
Median Time ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Response Rate ◽  
Complete Response ◽  
Infectious Complications ◽  
Hemoglobin Level ◽  
Published Data ◽  
Steroid Dependence

Abstract Abstract 3168 INTRODUCTION: Steroids are the first line treatment for Autoimmune Hemolytic Anemia (AHA) and Immune Thrombocytopenic Purpura (ITP). Second line treatments for patients with partial reponses or steroid dependence are controversial and have changed during the last decades. Several authors have proposed the use of Rituximab in these patients although published data are still sparse. OBJECTIVES: We reviewed the medical records of all the patients treated in our hospital with Rituximab in order to evaluate the response rate and security of this treatment. MATHERIALS AND METHODS: We included in the study all the patients older than 18 years with diagnoses of Immune Thrombocytopenia or Autoimmune Hemolytic Anemia treated with Rituximab. Patients with oncologic diseases that required specific chemotherapy apart from AHA or ITP were excluded. Rituximab was administered at a dose of 375mg/m3 weekly for 4 weeks. In patients with AHA we assessed the response according to the following criteria: complete response a hemoglobin level higher than 12 g/dl without hemolysis (normal bilirubin, LDH and haptoglobin) and partial response at least 2g/dl increase from the basal hemoglobin level with improvement in the hemolysis parameters. In patients with ITP we defined complete response as >100.000 platelets/mm3 and partial response >50.000 platelets/mm3. In both cases patients should be tapering steroids (less than 10mg/day of prednisone) and without transfusions. RESULTS: We performed 55 treatments with Rituximab in 37 pts., 19 AHA (12 cold hemolytic anemia) and 18 ITP. The median age was 60 years (26 – 86) and 31 pts. were female. Five patients had other autoimmune diseases (lupus, sjogren, autoimmune hepatitis), and six patients had an underlying onco-hematologyc disease (CLL, indolent lymphoma). All patients had been treated with steroids before and most of them had also received azathioprine, cyclophosphamide or gamaglobuline. The median of previous treatments was 3. Eight patients had undergone also splenectomy. The reason for the treatment was steroid dependence in 16 patients, partial response 6 patients and no response to previous treatment in 15 patients. The overall response rate was 79% for AHA and 94% for ITP, with 8pts (42%) and 13pts (72%) achieving a complete response and 7pts (37%) and 4pts (22%) achieving a partial response respectively. The median time to the complete response was 14 days for ITP and 28 days for AHA. The treatment was well tolerated with only one infusion related serious adverse event and one pulmonary thromboembolism during the period of treatment. Fourteen patients relapsed (8 AHA and 6 PTI). The response rate to Rituximab at relapsed for those patients that received a second or even third course of treatment were similar to the observed before. The median time of follow up was 50 months with and event free survival at 1 year of 34% (median 11,9 months) for AHA vs. 60% for PTI (median 38 months) (p 0,23). The overall survival at 5 years was 39% (median 53 months) vs. 86% (median not reached) (p 0,18) respectively. Seven patients with AHA and 2pts with ITP died, mostly of infectious complications. CONCLUSIONS: Rituximab is an effective treatment for ITP and AHA patients with no response to previous treatments or corticoid dependence. There were few serious adverse effects related to the treatment with Rituximab itself. The mortality rate was higher in patients with AHA although it wasn`t statistically significant. The main cause of death was related to infectious complications but most of the patients had a long history of immunosuppression treatment. Patients who relapsed and were treated again with rituximab had very good response rate. Disclosures: No relevant conflicts of interest to declare.

Anti-CD20 Monoclonal Antibody in the Treatment of Refractory Autoimmune Cytopenias in Adults.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2717-2717
Author(s):  
Santhosh Narat ◽  
Jagdish Gandla ◽  
Atul B. Mehta
Keyword(s):  
Monoclonal Antibody ◽  
Median Time ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Complete Response ◽  
Maximum Response ◽  
Maximal Response ◽  
Effective Treatment Option ◽  
Number Of Patients ◽  
Anti Cd20

Abstract Anti-CD20 monoclonal antibody (rituximab) has been used in autoimmune cytopenia with variable success.We report 13 patients with chronic refractory autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) who each received 4 cycles of rituximab 375mg/m2 weekly. All 8 AIHA patients (6 idiopathic,2 secondary to a lymphoproliferative disorder, 5 splenectomised) had warm antibody type. Response was seen in 4(50%) of 8 patients (3 CR,1PR) and 3 patients remain in CR at 5,7,14 months post-therapy. Median time to maximum response (TMR) in responders was 9 weeks(range 6 – 18 weeks). In 5 ITP patients (4 splenectomised), 4(80%) responded (3CR) and one continues in CR 50 weeks after completion of rituximab treatment Median time to maximum response was 4 weeks (range 4 – 12 weeks). No pre-treatment clinical or laboratory parameters that predict response could be identifird in the AIHA or ITP groups.Our data indicate that rituximab is a relatively safe and effective treatment option in patients with refractory autoimmune hemolytic anemia and thrombocytopenia. Table 1 Number of patients Mean age (Years) Sex Overall response Complete response No response Time to maximal response AIHA 8 47.75 (26– 73) 3M:4F 4 (50%) 3 (37.5%) 4 (50%) 9 weeks ITP 5 58.6 (28–89) 4M:1F 5 (80%) 3 (60%) 2 (40%) 4 weeks

Cyclophosphamide, Bortezomib and Dexamethasone (CyBORD) Is a Feasible and Active Regimen for Non-Transplant Eligible Multiple Myeloma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5751-5751 ◽  
Author(s):  
Victor H Jimenez Zepeda ◽  
Peter Duggan ◽  
Paola E. Neri ◽  
Nizar J Bahlis
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Median Time ◽  
Light Chain ◽  
Overall Response Rate ◽  
Response Rate ◽  
Complete Response ◽  
Overall Response ◽  
Novel Drugs ◽  
Good Partial Response

Abstract Introduction With the advent of novel drugs for the treatment of Multiple Myeloma (MM), the clinical outcomes have significantly improved over the last decade both in the setting of stem cell transplant eligible and non-eligible patients. Combinations of novel drugs have improved and deepened response and this is true for CyBORD, a regimen able to induce rapid and deep responses. Based on the above mentioned, we aimed to assess the role and feasibility of CyBORD as upfront therapy for non-transplant eligible patients with MM. Methods. All consecutive patients with documented symptomatic MM not eligible for transplant treated with CyBORD at our Institution were evaluated. Treatment consisted of a 28-day cycle of bortezomib 1.3 mg/m2 or 1.5 mg/m2 intravenously or subcutaneously on days 1, 8, and 15, cyclophosphamide 300 mg/m2 orally administered on days 1, 8, and 15 and dexamethasone 20-40 mg orally on weekly basis. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. The primary endpoint of the study was to assess the efficacy and feasibility of CyBORD in this group of patients. All analyses were performed using the SPSS 20.0 software and all p-values were 2-sided and statistically significant if <0.05. Results Between 07/11 and 07/14, 20 patients were identified for the study. Clinical and laboratory characteristics are listed in Table 1. The median age for this cohort of patients was 76 years (range 66-90). Sixty-five percent of patients had IgG isotype, 5% had IgA, and 30% had light chain only disease. After a median of 5 cycles, the overall response rate was 95% (19/20) with 70% of patients achieving VGPR or better response. (Table 2 ) The median time to first response was 6 weeks with majority of cases achieving at least PR after 2 cycles of therapy. At a median follow-up of 9.5 months, all patients are alive and 5 had already progressed at a median time of 12 months. With regards to toxicity, 6 patients experienced non-hematological grade 3/4 adverse events (20%), including muscle weakness, sepsis and pneumonia. Neutropenia and thrombocytopenia were seen in 2 patients (10%), both patients required dose reduction of cyclophosphamide with one patient being discontinued of cyclophosphamide after 2 cycles but still receiving bortezomib and dexamethasone. In conclusion, CyBORD is a highly active and viable option for the treatment of non-transplant eligible patients with MM. As suggested by other studies, elderly patients required dose adjustments and special considerations while receiving active therapy, balancing the efficacy and toxicity given by the different drug combinations. Table 1. Clinical and Laboratory characteristics of non-transplant eligible MM patients treated with CyBORD Characteristic N Median Range % Age (years) 20 76 66-90 Gender -Male -Female 11 9 55% 45% ISS Stage I II III 5 7 8 25% 35% 40% Heavy chain IgG IgA Free light chain only Light chainKappa Lambda 13 1 6 11 9 65% 5% 30% 55% 45% Hemoglobin (g/L) 20 106 73-158 Creatinine (µmol/L) 20 117 49-671 Calcium (µmol/L) 20 2.4 2.0-2.99 LDH (IU/L) 20 229 118-814 B2-microglobulin (mg/L) 20 4.1 1.41-19 Albumin (g/L) 20 32 22-37 FISH Cytogenetics Standard risk High risk 18 2 90% 10% Table 2. Response rates for non-transplant eligible MM patients treated with CyBORD Characteristic Median (Range) N % Number of cycles 5 (1-12) Overall Response rate 19/20 95% Near Complete Response Complete Response 1 2 5% 10% Very Good Partial Response 11 55% Partial Response 5 25% Less than PR 1 5% Progression 5/20 25% Time to progression (months) 12 (3-15) Alive 20 100% CyBORD: Cyclophosphamide, bortezomib and dexamethasone Disclosures Jimenez Zepeda: Janssen Ortho: Honoraria. Bahlis:Celgene: Honoraria, Research Funding.

scholarly journals Efficacy and Safety of Erythropoietic-Stimulating Agents with Ruxolitinib in Myelofibrosis Patients : A Retrospective Analysis on 45 Patients. on Behalf of the French Intergroup of Myeloproliferative Disorders (FIM)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3123-3123 ◽  
Author(s):  
Sandra Malak ◽  
Pascale Cony-Makhoul ◽  
Jean-Christophe Ianotto ◽  
Dana Ranta ◽  
Philippe Rodon ◽  
...  
Keyword(s):  
Partial Response ◽  
Retrospective Analysis ◽  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Real Life ◽  
Hemoglobin Level ◽  
Allogeneic Bone ◽  
Advisory Committees

Abstract Background Ruxolitinib is a current therapeutic option, which has demonstrated rapid and durable reduction in splenomegaly and improved disease-related symptoms in patients (pts) with primary myelofibrosis (PMF), post-polycythemia vera-MF (PPV-MF), and post-essential thrombocythemia-MF (PET-MF). Anemia is another frequent issue in MF, which may be managed by the use of ESA, leading to a 40-50% response rate in small studies. Consistent with its JAK2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need, especially during the first 12-24 weeks of treatment in the COMFORT studies. Despite potential antagonistic mechanisms of action on JAK2, some responses on anemia have been reported with the addition of ESA to ruxolitinib in a small subset of pts in the COMFORT II study. The present study aimed to better assess the efficacy of ESA on anemia related to ruxolitinib and tolerance of this combination in a larger cohort of pts treated for MF in general practice. Methods We performed an observational study on patients with MF previously or currently treated with concomitant ESA and Ruxolitinib in French centers members of the FIM. Informed consent was provided by the pts. Data collected included characteristics of the disease, treatment, responses to ruxolitinib and ESA. They are reported according to the IWG-MRT/ELN 2013 criteria. Results This analysis was performed in July 2016, on the 45 first consecutive pts in 11 centers. Median age at diagnosis was 73 (range 42- 89), 30 (67%) were men. Twenty-five pts (56%) had primary MF, 11 (24%) PET-MF and 9 (20%) PPV-MF, overall diagnosed between 2004 and 2016. IPSS risk categories were low/int-1 and int-2/high in 16 (36%) and 28 (64%) pts, respectively. Twenty-nine (64%) were JAK2V617F positive, 5 harbored MPL mutation and 8 had CALR mutations. Median time between MF diagnosis and ruxolitinib was 21 (0-109) months and median follow-up from ruxolitinib starting was 13 (2 - 53) months. At time of ruxolitinib initiation 32 (71%) pts were transfusion independent and 13(29%) had transfusion need. Ten additional pts became transfusion dependent after ruxolitinib initiation. Other causes of anemia were renal insufficiency n=7, surgery n=1, 1 cytoreductive therapy with hydroxyurea. Type of ESA were darbepoetin alfa, [n=26]; epoetin alfa, [n=3], epoetin beta [n=8], epoetin zeta [n=4], epoeitin theta [n=4], with a median duration of exposure to ESA of 15 months [1-92mo]. ESA was introduced either before ruxolitinib (n= 17), simultaneously (n= 4) or afterward (n= 24) after a median of 2 months [1-26mo]. Response rate to ruxolitinib were in accordance with previous reports: For splenomegaly, 33 (73%) of pts achieved at least a partial response, 8 (17%) were stable and 4 (9%) were progressive. Thirty pts (67%) had at least partial response on constitutional symptoms. Response assessment of anemia according to IWG-MRT/ELN 2013 criteria: 7 pts (16%) achieved a RBC transfusion independency, 13 (29%) pts had an increase in hemoglobin level of Hb >2g/dl (2 pts achieved both criteria), which results in 40% of objective responses. The median time to best response on anemia after ESA initiation was 3 [1-84] months. For safety, a pulmonary embolism occurred in one patient possibly related to ESA, no other adverse event occurred, in particular no spleen enlargement was described. At time of analysis, 36/45 pts were still alive: 1 underwent allogeneic bone marrow transplant, 34 were still treated with ruxolitinib whereas 28 patients were still undergoing ESA therapy. Conclusions This retrospective analysis is the largest cohort describing the use of concomitant ESA with ruxolitinib therapy in "real life". We report 40 % of objective responses, consistent with ESA response rates without ruxolitinib for MF related anemia. Tolerance seemed acceptable without hampering efficiency of ruxolitinib. Our results suggest that ESA should be considered as a possible therapeutic for anemia in myelofibrosis patients treated with ruxolitinib. Disclosures Malak: Novartis: Membership on an entity's Board of Directors or advisory committees. Ugo:Novartis: Membership on an entity's Board of Directors or advisory committees. Kiladjian:Novartis: Research Funding; AOP Orphan: Research Funding. Roy:AOP: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: congress travel, Research Funding.

Risk Profile, Efficacy and Safety of Rituximab in Patients with Relapsed or Refractory Idiopathic Thrombocytopenic Purpura in a Minority Cohort with Long Term Follow up

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4546-4546
Author(s):  
Shylendra B Sreenivasappa ◽  
R. Catchatourian ◽  
Barbara Yim
Keyword(s):  
Platelet Count ◽  
Partial Response ◽  
Median Time ◽  
Response Rate ◽  
Complete Response ◽  
Thrombocytopenic Purpura ◽  
Significant Difference ◽  
Time To Relapse ◽  
Refractory Itp

Abstract Background: Idiopathic Thrombocytopenic Purpura (ITP) is a common hematological disorder. We sort to characterize the risk profiles and efficacy of rituximab in relapsed or refractory ITP in a largely minority cohort. Methods: 23 patients (pts) with relapsed or refractory ITP treated with Rituximab were identified and studied as a retrospective cohort. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student’s T test, categorical data via Fisher’s exact test and time to progression data was analyzed via Kaplan Meier life table analysis and log rank test. Results: Of the 23 patients, 20 female (87%), 3 male (13%). median age at diagnosis was 45 yr (range 20–66).9 pt were African American (39%), 9 Hispanics (39%), 4 Asian (17.4%), 1 Caucasian(4.3%), 9 (39.6%) had more than one co morbidities, 17 (73.8%) had received 3 or more treatment regimens. All pt received steroids, 18 (78.3%) received IVIg, 13 (56.6%) Anti D immunoglobulin, 5 (21.7%) Vincristine, 3 (13%) Azathioprine, 2(8.7%) Cyclophosamide, 6 (26.1%) underwent a Splenectomy before Rituximab therapy. The median time from diagnosis to rituximab therapy was 15 months (range 1 to 269). Median platelet count before rituximab therapy was 11 (range 3 to 200). Rituximab was administered at the dose of 375mg/m2 IV once a week for 4 weeks. The response rate was 47.8%. Response was defined as Complete response, platelet count of &gt; 100 × 109/L, Partial response &gt;50 × 109/L. 9 pt (39%) achieved complete response, 2 pt (8.7%) achieved partial response. 12 pt (52.2%) did not respond. Median time to response was 13.5 days (range 1–30). There was no statistically significant difference in the response when compared by gender (p=0.64), race (p= 0.398), prior splenectomy (p=0.64), prior anti D immunoglobulin (p=1.0), prior Vincristine (p=1.0), prior cyclophosamide (p=.45), prior azathioprine (p=1.0). Four pt (17.4%) had a serious adverse reaction to rituximab. One pt had diffuse hives after infusion, three pt developed diffuse pancytopenia, two pts had gram negative sepsis and died. The median follow up after rituximab therapy was 18 months (range 1–60). The median time to relapse was 7 months (range of 1 to 59). There was no statistically significant difference in time to relapse among gender (p=0.19), race (p= 0.45), Prior splenectomy (p=0.86), prior Anti D immunoglobulin (p=0.32), prior vincristine (p=0.75). Conclusion: In this primarily minority based cohort the response rate to Rituximab (48% vs. 62%) and duration of response (7 months vs. 10.5 months) was lower than other published data but the rate of serious adverse events (17% vs. 7%) was higher. Rituximab must be used cautiously in this sub group of patients. There is need for a randomized controlled clinical trail to assess the efficacy of Rituximab in this population and further studies are warranted in minority populations.

scholarly journals Low Dose Rituximab Plus High Dose Dexamethasone As First-Line Treatment for Autoimmune Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Carlos Saúl Rodríguez-Roque ◽  
Andres Gomez-De Leon ◽  
Michelle Morcos-Sandino ◽  
Nelson Josafat López-Flores ◽  
David David Galindo-Calvillo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Low Dose ◽  
Complete Response ◽  
Event Free Survival ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
Loss Of Response

Introduction Corticosteroids are the first line therapy for autoimmune hemolytic anemia (AIHA), but are associated with significant adverse events, dependency and frequent relapses. Rituximab is reserved for severe or steroid-resistant disease. Low-dose rituximab is also effective, but its efficacy in the first line has been poorly described. We report our results with this combination. Methods Adults older than 16 years newly diagnosed with warm antibody AIHA either primary or secondary were included. Patients systematically received dexamethasone 40 mg for 4 days followed by a 1 mg/kg rapid prednisone taper plus rituximab 100 mg weekly for 4 doses. Our primary outcome was response at day 28 based on the First International Consensus Meeting (complete response: normalization of Hb, no evidence of hemolysis and absence of transfusions; response: increase of Hb by &gt;2g/dl, or normalization of biochemical resolution of hemolysis or absence of transfusion in 7 days), secondary outcome was event-free survival with an event defined as a laboratory or clinical relapse or loss of response. Results Sixteen patients were treated with low-dose rituximab during the study period, ten women (62.5%), six men (37.5%). The median age was 34 years (range, 17-78). Three (18.75%) were secondary to lupus erythematosus. The median follow-up was 20 months (range, 0.4-66). Most received 4 doses of rituximab (87.5%). All patients responded at day 28, (100%) 31.2% achieved a complete response (CR). Subsequently, 81.3% achieved CR. Ten (62.5%) were considered steroid-dependent, however, most discontinued treatment without loss of response (75%). The event-free survival was 63.8% to 5 years. Conclusion Low-dose rituximab therapy as a first-line in AIHA showed encouraging results as most patients were able to discontinue treatment without relapse. Disclosures Gomez-Almaguer: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Walter Hanel ◽  
Beth A. Christian ◽  
Kami J. Maddocks ◽  
Narendranath Epperla ◽  
Basem M. William ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Immune Escape ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Median Number ◽  
Hodgkin's Lymphoma ◽  
Advisory Committees

Introduction: Classical Hodgkin's Lymphoma (cHL) is characterized by an extensive inflammatory infiltrate with abundant Th2 and Treg cells which facilitate immune escape of Reed Sternberg (RS) cells and provides a growth promoting microenvironment by cytokine secretion and CD40/CD40L engagement. Our group previously show that ibrutinib irreversibly inhibits both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), a kinase important in Th2 signaling (Dubovsky et al Blood 2013). We hypothesized that the addition of ibrutinib to nivolumab would lead to deeper and more durable responses in cHL by normalizing the Th1/Th2 balance thus reversing immune escape of RS cells. We present results of a planned interim analysis of the first 10 patients enrolled with a data cutoff of June of 2020. Methods: This is a single arm, phase II, single institutional clinical trial testing the clinical activity of nivolumab in combination with ibrutinib in patients ≥18 years of age with histologically confirmed cHL who have received at least one prior line of therapy and who were either not candidates for or had a prior autologous stem cell transplant (ASCT). Prior treatment with nivolumab was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for 16 cycles. The primary objective was complete response rate (CRR) prior to cycle 7 assessed per Lugano criteria. Adverse events (AEs) were reported using CTCAE Version 4.0. Results: Of the first 11 cHL patients enrolled, one patient withdrew consent prior to initiating therapy. Of the remaining 10 patients, the median age was 41 years (range 20-84) and 4 patients (40%) were male. The median number of prior lines of treatment was 4.5 (range 1-11), 5 patients (50%) had prior ASCT, 8 patients (80%) had prior brentuximab, and 5 patients (50%) had prior nivolumab. Four of the five patients with prior nivolumab had progressed while receiving therapy while the remaining patient had stable disease upon completing nivolumab with a median time from the last nivolumab treatment of 15.6 months (range 0.7-23.2). Of the 10 patients who received treatment, one patient came off study after two cycles due to persistent grade 2 transaminitis lasting for several weeks attributed to nivolumab requiring high dose oral steroids. One patient came off study after cycle 9 due to grade 3 hematuria attributed to ibrutinib and another came off study due to a pericardial effusion after 8 cycles of ibrutinib maintenance. In the remaining patients, treatment was generally well tolerated with most AEs being grade 1-2 (Table 1). The median number of total cycles received was 9 (range 2-22). Of the 9 patients evaluable for response, 6 patients responded (ORR = 66%), 4 of whom had a complete response (CRR = 44%) with a median time to response of 2 months (Table 2, Fig.1). In intention-to-treat analysis, the ORR was 60% and CRR was 40% meeting our prespecified interim efficacy endpoint of a 30% CRR for trial continuation. Notably, of the 5 patients with prior nivolumab, 3 responded to nivolumab + ibrutinib (ORR = 60%), with one having a CR (CRR = 20%). Overall, at a median follow up of 9.5 months, both the median PFS and duration of response have not yet been reached, with 3 patients remaining in CR at the time of data cutoff. Three of 4 patients discontinued trial treatment to undergo SCT [2 allogeneic; 1 autologous]. Of the 2 allogeneic SCT patients, the first one underwent SCT 3 weeks after the last nivolumab infusion and developed multi-organ acute graft-versus-host disease (GVHD) followed by severe chronic GVHD requiring extracorporeal photopheresis. The second patient underwent allogeneic SCT 2 months following the last nivolumab infusion and had no acute GVHD and experienced only mild chronic GVHD which was medically managed. Conclusions: Although the numbers are small and further recruitment is ongoing (target n=17), the combination of ibrutinib and nivolumab was generally well tolerated and with high response rate with more than half of responding patients achieving a CR. In addition, responses were seen in patients with prior nivolumab treatment. Our results suggest a possible novel role for BTK inhibition in reversing nivolumab resistance in cHL, at least in some cases. Correlative studies including peripheral blood and tumor immune subset analyses are ongoing and the latest results will be presented at the meeting. Disclosures Christian: Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Maddocks:Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. William:Incyte: Research Funding; Dova: Research Funding; Celgene: Consultancy, Honoraria; Seattle Genetics: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Guidepoint Global: Consultancy. Jaglowski:Novartis: Consultancy, Research Funding; CRISPR: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy. Bond:Seattle Genetics: Honoraria. Brammer:Celgene Corporation: Research Funding; Seattle Genetics, Inc.: Speakers Bureau. Baiocchi:viracta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Consultancy, Research Funding. OffLabel Disclosure: This trial uses ibrutnib in cHL to augment the responses of concurrent nivolumab administration.

scholarly journals Long-term clinical course and outcomes of immunoglobulin G4-related lung disease

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jieun Kang ◽  
Shinhee Park ◽  
Eun Jin Chae ◽  
Joon Seon Song ◽  
Hee Sang Hwang ◽  
...  
Keyword(s):  
Lung Function ◽  
Partial Response ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Treatment Outcomes ◽  
Response Rate ◽  
Clinical Course ◽  
Complete Response ◽  
Immunoglobulin G4

Abstract Background Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. Methods Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. Results The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. Conclusions Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia

2019 ◽  
Vol 143 (3) ◽  
pp. 244-249 ◽  
Author(s):  
Caroline I. Piatek ◽  
Hillel Bocian ◽  
Sandra Algaze ◽  
Ilene C. Weitz ◽  
Casey O'Connell ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Immune Modulation ◽  
Complete Response ◽  
Primary Objective ◽  
Additional Treatment ◽  
Lymphocytic Leukemia ◽  
Immunocompromised Patients ◽  
Treatment Changes

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10–11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2–6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3–12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6–15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

Autologous Transplantation for Aggressive Non-Hodgkin’s Lymphoma: Results of a Randomized Trial Evaluating Graft Source and Minimal Residual Disease

2002 ◽  
Vol 20 (9) ◽  
pp. 2344-2352 ◽  
Author(s):  
Julie M. Vose ◽  
Graham Sharp ◽  
Wing C. Chan ◽  
Craig Nichols ◽  
Kevin Loh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Response Rate ◽  
Complete Response Rate ◽  
Residual Disease ◽  
Complete Response ◽  
Hematopoietic Stem ◽  
Transfusion Independence ◽  
Rbc Transfusion ◽  
Minimal Residual

PURPOSE: To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) for aggressive non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Of 105 high-risk, persistent, or relapsed NHL patients slated for an autologous HSCT entered onto this trial, 93 eligible patients were randomized to receive cytokine-naive autologous bone marrow transplantation (ABMT) (n = 46) or mobilized peripheral-blood stem-cell transplantation (PBSCT) (n = 47). All patients received carmustine, etoposide, cytarabine, and cyclophosphamide as the conditioning regimen. PBSCT patients also received identical mobilization with granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/d, and both groups received G-CSF 5 μg/kg/d after the infusion of the stem-cell product until neutrophil engraftment. RESULTS: PBSCT patients had significantly faster engraftment of all cell lineages: median time to absolute neutrophil count ≥ 500/μL, 10 days versus 13 days on the ABMT arm; median time to platelet count greater than 20,000/μL untransfused, 11 days versus 15 days on the ABMT arm; and median time to RBC transfusion independence, 8 days versus 16 days on the ABMT arm. The complete response rate was 72% for PBSCT and 54% for ABMT. The death rate before posttransplant day 100 was 2% on the ABMT arm and 6% on PBSCT arm. Event-free survival was 37% for PBSCT and 37% for ABMT. However, overall survival for PBSCT was 61% compared with 43% for ABMT. CONCLUSION: Patients with aggressive NHL receiving HSCT randomized to PBSCT demonstrated improved neutrophil engraftment and platelet and RBC transfusion independence. The complete response rate and EFS were not statistically different by randomization arm. Patients whose harvests were positive for minimal residual disease by molecular analysis had poorer EFS.

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