Omalizumab: Efficacy and Safety in Mast Cell Disorders

Abstract Background. Patients with mast cell diseases may suffer from various distressing symptoms, which can be insufficiently controlled with available therapies, severely affecting quality of life. There is thus a need for new and safe treatment options for these patients. Objectives. We aimed to evaluate safety and efficacy of omalizumab administration in patients with a systemic mast cell disorder. Methods. We included 56 patients with a systemic mast cell disorder who received omalizumab treatment between January 2015 and December 2017, after a pluridisciplinary review at the French National Reference Center for Mastocytosis (CEREMAST). Results. A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (53.6%) and a partial response for 12 patients (21.4%), resulting in an overall response rate of 76.8% (43/56 patients). The response was persistent at least 3 months in 33 patients (58.9%). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms (Figure 1). Safety profile was acceptable, except for one severe adverse event (cervical edema and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (28.6%), mainly of low to mild intensity, yet causing interruption of treatment in 6 patients (10.7%). Conclusion. Omalizumab is an effective treatment option in systemic mast cell disorders, and displays a favorable safety profile. Prospective studies remain necessary to confirm these encouraging results. Disclosures No relevant conflicts of interest to declare.

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Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽

10.1182/blood.v120.21.5036.5036 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5036-5036 ◽

Cited By ~ 1

Author(s):

Beihui Huang ◽

Juan Li ◽

Junru Liu ◽

Dong Zheng ◽

Mei Chen ◽

...

Keyword(s):

Multiple Myeloma ◽

Side Effects ◽

Light Chain ◽

Conflicts Of Interest ◽

Complete Response ◽

Al Amyloidosis ◽

Newly Diagnosed ◽

Hematologic Response ◽

Best Response ◽

Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v104.11.2717.2717 ◽

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

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Alemtuzumab for Treatment of Refractory Evans Syndrome

Blood ◽

10.1182/blood.v126.23.4542.4542 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4542-4542

Author(s):

Timothy O'Brien

Keyword(s):

Single Case ◽

Treatment Options ◽

Complete Response ◽

Infectious Complications ◽

Severe Thrombocytopenia ◽

Evans Syndrome ◽

Small Series ◽

Humanized Monoclonal Antibody ◽

Heavily Pretreated ◽

Cell Disorder

Abstract Background: There are limited treatment options for refractory Evans syndrome. After steroids and splenectomy, rituximab has been used w/some success. Alemtuzumab, a humanized monoclonal antibody against CD52, has been reported in small series of autoimmune hemolytic anemia (AIHA), usually in pts w/an underlying B-cell disorder such as CLL, but does not appear to have been reported in Evans syndrome. Methods: Chart review of a single case. Results: A 53 year old Caucasian man was admitted in 12/2012 with severe AIHA and thrombocytopenia. He was originally diagnosed with ITP at age 19, treated with steroids and later a splenectomy, then at age 40 (1999) presented with severe AIHA and thrombocytopenia, and was diagnosed with Evans syndrome. This was refractory to steroids, IVIG, vincristine and cyclophosphamide, but responded to an immunoadsorption column; he relapsed in 2005 and 2007, each time with predominantly isolated severe thrombocytopenia, which was treated successfully each time with weekly x 4 rituximab. He relapsed again in 3/2010, treated again with rituximab w/resolution of thrombocytopenia, but with recurrence of severe AIHA: DAT+ (IgG); hgb nadir 4.8gm/dL; LDH 1916 IU, TBili 10.4 mg/dL (direct bilirubin 1.1); retic count peaked at 52%. The severe anemia was refractory to steroids, IVIG, cyclophosphamide and vincristine (immunoadsorption column no longer available in the U.S.). He was then treated with intravenous alemtuzumab (3mg x 1 day then 10mg x 1 day then 30mg 3x/week x 4 weeks). 3 weeks after starting alemtuzumab there was a response, with improvement in hemolysis parameters (LDH 632, TBili 1.4, retic count 1.6%) and anemia (hgb 8.5, without transfusion support). By 4 weeks there was a complete normalization of hemolysis parameters (LDH 199, Tbili 1.2, retic 1%) and continued hemoglobin improvement (9.1), which normalized by week 12. He remained in remission for 10 months until he developed relapse of ITP in 5/2011, which was refractory to rituximab and was then started on romiplastin in 6/2011, with normalization of platelet counts. He remained in remission until 11/2012 when he developed severe thrombocytopenia (plt=3k), refractory to increasing doses of romiplastin, and then developed severe AIHA in late 12/2012 (hgb nadir 4.5; LDH 1070; retic 26%) with persistent severe thrombocytopenia (plt=2k). He was re-started on alemtuzumab from 12/30/12 to late 1/2013, dosed as before, with near complete resolution of thrombocytopenia (plt incremented to 138k) and hemolysis (LDH 195, retic 5%) by week 4, with improvement in hgb (to 8.3). He then relapsed with severe AIHA in mid 3/2013 (hgb 5.1) and was restarted on alemtuzumab; there was no response in hemolysis parameters so cyclosporine was added; alemtuzumab was stopped on 4/24/13; he was tried again on rituximab on 5/10/13. He developed worsening, refractory AIHA, with renal and hepatic failure and, unfortunately, passed away on 5/24/13. During the alemtuzumab treatments he received prophylactic acyclovir, PCP prophylaxis and had weekly surveillance CMV DNA testing. He did not develop any CMV or other infectious complications. Conclusions: Alemtuzumab administration resulted in a complete response lasting 10 months (and 29 months for the severe AIHA) and a 2nd near complete response lasting 2 months in a very heavily pretreated man w/Evans syndrome. Use of this medication should be considered as another treatment option in the management of refractory cases. Disclosures Off Label Use: alemtuzumab in the treatment of Evans syndrome.

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Efficacy and Safety of Re-Treatment with Bortezomib (Velcade©) in Patients with Multiple Myeloma: Results from a Prospective International Phase II Trial

Blood ◽

10.1182/blood.v112.11.3690.3690 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3690-3690 ◽

Cited By ~ 5

Author(s):

Maria Teresa Petrucci ◽

Igor W. Blau ◽

Paolo Corradini ◽

Meletios A. Dimopoulos ◽

Johannes Drach ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Median Time ◽

Safety Profile ◽

Phase Ii Trial ◽

Efficacy And Safety ◽

Bortezomib Treatment ◽

Free Interval ◽

Best Response ◽

Grade 3

Abstract Background: Bortezomib has been shown to be effective in the treatment of multiple myeloma (MM). However, the data on response to re-treatment with bortezomib is very limited, mostly coming from small retrospective studies. Response to re-treatment is particularly relevant in patients with relapsing incurable conditions such as MM. The primary objective of this first international prospective phase II trial was to determine the best response to bortezomib re-treatment in patients with MM. Secondary objectives included safety profile, duration of response, time to progression, best M protein response and the evaluation of the best investigator-assessed response compared to the best response reported to the previous bortezomib treatment. Methods: Patients with secretory MM were eligible if they had responded (CR or PR) to a bortezomib-based most recent treatment and had a treatment-free interval of at least 6 months since the last bortezomib dose. They needed to meet the PD criteria as defined by European Group for Blood and Marrow Transplantation (EBMT). Patients received bortezomib starting at the last tolerated dose in the previous bortezomib regimen (1.3 or 1.0 mg/m2). Bortezomib was administered alone or in combination with dexamethasone at investigator discretion. Bortezomib was administered as an intravenous injection on days 1, 4, 8 and 11 of a 21-day cycle up to a maximum of 8 cycles. Response was evaluated every 6 weeks according to EBMT criteria. Adverse events (AEs) were assessed from informed consent until at least 30 days after treatment and were graded by the NCI-CTCAE. This clinical trial closed to recruitment on 30th June 2008 after reaching the planned sample size of 128 patients, with 57 patients still receiving treatment. The results presented include the efficacy and safety data available for 100 patients who had completed at least 2 treatment cycles at the time of data cut-off (16 July 2008) or who had withdrawn from therapy for any reason. Results: The 100 patients (M: 59, F: 41; median age 66 years) who received at least 1 dose of bortezomib are included in the current safety analysis. The median time from diagnosis of MM was 4.5 years (range 0–14 years) and 59% had received 3 or more lines of prior therapy (including the previous bortezomib therapy). Karnofsky performance status was £ 70% in 16% of patients. Twenty-six percent of patients had achieved a complete response (CR) with the last bortezomib regimen. The median treatment free interval since the previous bortezomib treatment was 14.3 months. Eighty-seven percent of the patients received at least 3 cycles and the median number of completed cycles was 5 cycles. Dexamethasone was added to the bortezomib treatment in 69% of patients. In the 97 patients eligible for the current efficacy analysis, the overall response rate (ORR) by EBMT criteria [CR+PR] was 26.8% (CI=18.3– 36.8), with 3.1% complete responses, whilst ORR + minimal response (MR) was 46.4%. The ORR did not differ in patients treated with bortezomib plus dexamethasone (27.9%, CI=17.7– 40.1) versus those treated with bortezomib alone (24.1%, CI=10.3–43.5). The median time to at least PR was 43 days, with a median time to best response of 64 days. The most commonly reported related grade 3/4 adverse events were thrombocytopenia (24%), neutropenia (5%) and diarrhea (5%). Peripheral neuropathy (PN) was observed in 20% of patients, with grade 3 PN reported in 6% of patients only. Serious TEAE’s were reported in 23% of patients and 10% of patients discontinued bortezomib due to related TEAE’s including 6 cases of PN. TEAE’s leading to death were reported in three patients. Conclusions: Response after re-treatment with bortezomib alone or in combination with dexamethasone in heavily pre-treated multiple myeloma patients was still high, and the adverse event profile was consistent with the already known safety profile. Updated results will be presented at time of the meeting.

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The Combination of Azacitidine (AZA) and Recombinant Erythropoietin (rEPO) Can Induce Rapidly Hematological Response In Intermediate-2 and High-risk MDS (including RAEB-t)

Blood ◽

10.1182/blood.v116.21.2914.2914 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2914-2914

Author(s):

Haris Kartsios ◽

Kostas Loukidis ◽

Vassilios Papadopoulos ◽

Smaragda Effraimidou ◽

Anastasia Spyrou ◽

...

Keyword(s):

Median Time ◽

Conflicts Of Interest ◽

Laboratory Data ◽

Progression Free Survival ◽

Recombinant Erythropoietin ◽

Platelet Response ◽

Erythroid Response ◽

Best Response ◽

Neutrophil Response

Abstract Abstract 2914 Background: AZA, a DNA hypomethylating agent, provides 50–60% responses in higher-risk MDS after administration of 6 courses of treatment. Recent laboratory data suggests that demethylation with AZA upregulates EPO-receptor mRNA (Wallach, 2009). AZA might also affect several genes involved in cell cycle, metabolism and signal transduction which are down-regulated in bone marrow erythroid cells in MDS patients non-responsive to rEPO. There is currently insufficient data to combine AZA and rEPO in MDS patients. Patients-Methods: We explored the safety and the efficacy of the AZA-rEPO combination in a cohort of 10 (M/F: 5/5) patients (pts) with a median age of 75(67-83) years. Diagnosis (WHO classification) was: RAEB-2: 5, CMML: 2 and RAEB-t: 3; IPSS was: int-2 in 8/10 and high in 2/10 pts. Median time from diagnosis was 6(1-31) months. 9/10 pts were transfusion dependent, 8/10 were refractory to previous rEPO administration while 2/10 pts were not treated with rEPO but their diagnostic serum EPO levels were >200 U/L. Patients were given AZA at FDA/EMEA-approved schedule (75 mg/m2/d x7d/4-weekly) initially for 5 courses and continued if response was obtained. rEPO (40,000IU/week) was given until achievement of steady Hb level >10.5 g/dL or until AZA discontinuation. Results: Median follow-up was 6.5(1-14) months. Patients received a median of 5 cycles (range 2–13) of AZA; 9/10 pts were treated with ≥5 courses of AZA. The median time of rEPO administration was 82(76-142) days. Best response (IWG 2006 criteria) was CR in 1/10 pts (RAEB-2: 1), marrow CR in 1/10 pts (RAEB-t: 1), and stable disease with hematological improvement (HI) in 4/10 pts (RAEB-t: 1, RAEB-2: 2, CMML: 1) leading to an overall response rate of 60%. As soon as 2 courses of AZA-rEPO were given, 5/6 responders experienced HI-erythroid response, 3/6 obtained HI-platelet response and 2/6 achieved HI-neutrophil response. Adverse events included 2 episodes of febrile neutropenia, nausea (2/10 pts), reversible renal impairment (2/10 pts) and hemorrhagic complications (3/10 patients). Currently, 9/10 patients remain alive, 1 patient experienced progression to AML and the estimated probability of 1 year-Progression Free Survival is 75%. Conclusions: This study provides clinical evidence that the AZA-rEPO combination is safe and rapidly effective in higher risk MDS pts. Our results emphasize the necessity for randomized trials in order to further evaluate the AZA-rEPO combination in MDS. Disclosures: No relevant conflicts of interest to declare.

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Chlorambucil PLUS Rituximab As FRONT-LINE THERAPY in Elderly or Unfit Patients Affected by B-CELL Chronic Lymphocytic Leukemia: Results of A Single-Centre Retrospective Analysis

Blood ◽

10.1182/blood.v120.21.4604.4604 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4604-4604

Author(s):

Luca Laurenti ◽

Barbara Vannata ◽

Idanna Innocenti ◽

Francesco Autore ◽

Francesco Santini ◽

...

Keyword(s):

Median Time ◽

Conflicts Of Interest ◽

Complete Response ◽

Fish Analysis ◽

Median Dose ◽

Bulky Disease ◽

Overall Response ◽

Line Therapy ◽

Trisomy 12 ◽

Unfit Patients

Abstract Abstract 4604 Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl). However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 23 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg monthly for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). Fifteen patients were male and 8 were female, with a median age at the time of treatment of 70 years (range 58 to 81 years). Eight patients (35%) were unfit with a median age of 68 years (range 58 to 79 years). Five patients were in stage A/I, 10 were in stage B/II and 8 in stage C/IV. FISH analysis was done in all patients: 78% showed karyotype abnormalities. Low-risk FISH karyotype was detected in 20/23 pts: 12 of them had del(13q14), 1 had trisomy 12, 1 trisomy 12 and del(13q14) and 6 had a normal karyotype. Three patients showed a high risk karyotype: all of them had del(11q). None of the patients had a 17p deletion. Nineteen pts were studied for IGHV mutational status (83%), 12 had unmutated while 7 had mutated IGHV genes. Twenty-one patients were evaluable for response to treatment. The median number of Chl and RTX cycles administered in the 21 patients who completed the treatment protocol was 8 (range 6 to 8 cycles) and 6 (range 4 to 6 cycles) respectively. The median total dose of Chl administered during the treatment was 600 mg per patient (median dose 85 mg each cycle). The median dose of RTX administered was 4000 mg per patient (median dose 710 mg each cycle). Among 21 pts evaluable for response, the Overall Response Rate (ORR) was 76%. Six pts (28%) obtained a complete response, 10 pts (48%) obtained a partial response. No significant statistical differences were noticed in terms of ORR for age more or less than 70 years, fitness status, bulky disease, cytogenetic risk abnormalities or IgVH, ZAP-70 and CD38 categories. On an intention to treat basis the median PFS was not reached at a median time of 21 months (range 2–45). Eleven pts experienced progression after treatment at a median time of 20 months (range 2–36). No significant statistical differences were found among the analyzed risk groups. After a median time of 25 months (range, 2–45 months), TTR was not reached. No significant statistical differences were noticed between the Unmutated and Mutated IgVH groups and for ZAP-70 and CD38 categories with respect to TTR. At present the median follow-up is 29 months, with an OS rate of 80% (19/23). None of the risk factors analyzed were found to influence significantly the OS. In conclusion, this study suggests that the combination Chl-R is a safe and effective therapeutic option for untreated B-CLL pts that are not eligible for fludarabine treatment because of age and/or comorbidities. A multicentre trial to confirm these data is planned. Disclosures: No relevant conflicts of interest to declare.

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The Results of the Russian Registry of Primary Immune Thrombocytopenia (ITP) in Adults

Blood ◽

10.1182/blood.v126.23.4642.4642 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4642-4642

Author(s):

Igor Lisukov ◽

Alexey Maschan ◽

Anastasia Shamardina ◽

Tatyana Chagorova ◽

Igor Davydkin ◽

...

Keyword(s):

Partial Response ◽

Conflicts Of Interest ◽

Disease Onset ◽

Complete Response ◽

Newly Diagnosed ◽

Chronic Itp ◽

Best Response ◽

History Of ◽

Clinically Significant ◽

Observation Period

Abstract Study objectives The aim of the study was to evaluate disease characteristics and treatment practices of ITP in Russia. Materials and methods The ITP Registry was a multicenter, prospective, observational cohort study. The observation period for each patient in the Registry was not less than 12 months. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient. Exclusion criteria: secondary thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics was used. Patients were registered since June 2011 till June 2014. Results Five hundred and seven adult 394female (77.7%)/113 male(22.3%) pts from 26 hematology centers in various regions of the Russian Federation were included. Observation period ranged from 1.4 to 29.8 months with an average of 18.6 ± 6.2 mo. Median age was 50.2 years (range 18.6-89.1). Median disease duration was 1.83 years (range 0-56.07). History of ITP of lasting < 1 year was reported in 186 (36.7%) pts, 1-5 years - in 142 (28%), 5-10 years - in 56 (11%), over 10 years - in 87 (17.2%), and was considered as unknown - in 36 (7.1%). Newly diagnosed ITP was reported in 19.5% of adult pts; persistent - in 16.6% and chronic ITP - in 63.9% of pts, respectively. Median platelets count was 14,0 x 109/L (range 0.0- 119.0 x 109/L). Hemorrhagic manifestations in the history of ITP were reported in 92.5% of pts: skin hemorrhages - in 89.5% of pts, oral bleeding - in 50.3% , epistaxis - in 37.3% , gastrointestinal bleeding - in 7.7%, intracranial bleeding - in 0.4%, hematuria - in 4.5%, and other hemorrhages - in 20.9% of pts. Severe ITP at the time of enrollment was observed in 158 (31.2%) pts (104 pts (20.5%) had a clinically significant bleeding at the disease onset, and 54 (10.7%) pts developed new clinically significant hemorrhages during the treatment. Refractory ITP at the time of enrollment was reported in 100 (19.7%) pts (resistance to the first, second and subsequent lines of therapy in 62 (12.2%) pts); 38 (7.5%) pts did not respond to splenectomy. At the time of enrollment, 250 (49.3%) pts received medical treatment for ITP. Severe ITP after enrollment was observed in 124 (24.8%) adult pts. Throughout the study, various hemorrhagic manifestations of ITP were reported in 48.0% of pts, severe hemorrhagic syndrome was reported in 10.0% of pts; Before enrollment, splenectomy was reported in 94 pts (18.5%); complete response (CR) was maintained in 34 (36.2%) pts, partial response - in 20 (21.3%), and no response - in 7 (7.4%). Thirty-two (34.0%) pts had lost the response after initial success. During the study, splenectomy was performed in 44 (10.8%) pts, of those - in 7 pts (15.9%) with newly diagnosed ITP; in 6 pts (13.6%) - with persistent ITP, and in 31 pts (70.5%) - with chronic ITP. The duration of the disease at the time of splenectomy varied from 0 to 21 yrs; with a median of 1.03 year. CR to splenectomy was observed in 31 (70.5%) pts, partial response - in 10 (22.7%), and no response in 1 (2.3%), while 2 (4.5%) pts lost response. Since the response to splenectomy might change during the observation in the study, the best response was registered. Table 1. Distribution of the best response to splenectomy variable (before study entry and in the course of the study). Number of Pts (n) % Best response to splenectomy Missing data 1 0.7% Complete response 65 47.1% A response 30 21.7% No response 8 5.8% Loss of response 34 24.6% Total 138 100% Two hundred and forty-three (47.9%) pts received their first-line treatment during the study; glucocorticosteroids (GCS) - 222 (91.3%) pts, immunoglobulins (IVIG) - 2 pts (0.8%), other drugs - 26 (10.7 %) pts. A second-line therapy was administered to 133 pts (26.23%), of which 27 (20.3%) received GCS, IVIG - 23 (17.3%), alfa-interferons - 6 (4.5%), immunosuppressants - 8 (6%), rituximab - 18 (13.53%), romiplostim - 39 (29.3%), eltrombopag - 37 (27.8%), other drugs - 2 (1.5%) pts. Conclusion For the first time in Russia, information regarding the clinical presentation and the "real life" management practice of adults with primary ITP was obtained in a large cohort of pts in a prospective study. The Registry showed a variability of ITP clinical course. One fifth of pts were refractory to therapy. The main therapy options for the ≥ 2nd line in a cohort of adult pts were splenectomy and TPO receptor agonists. However, large proportion of pts still received GCSs in the 2nd and even 3rd line of therapy. Disclosures No relevant conflicts of interest to declare.

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Outcomes of Patients with Myelodysplastic Syndromes (MDS) Who Achieve Stable Disease after Treatment with Hypomethylating Agents (HMA)

Blood ◽

10.1182/blood.v124.21.3273.3273 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3273-3273 ◽

Cited By ~ 3

Author(s):

Aziz Nazha ◽

Mikkael A. Sekeres ◽

Guillermo Garcia-Manero ◽

John Barnard ◽

Najla H Al Ali ◽

...

Keyword(s):

Clinical Trial ◽

Median Time ◽

Stable Disease ◽

Conflicts Of Interest ◽

Initial Assessment ◽

International Prognostic Scoring System ◽

Fisher Exact Test ◽

Best Response ◽

Similar Survival

Abstract Background The primary treatment goal in higher-risk MDS patients (pts) is to prolong survival by altering the natural history of the disease and delaying progression to acute myeloid leukemia (AML). Treatment with HMA such as azacitidine (AZA) improves overall survival (OS) in pts who achieve a response of stable disease (SD) or better (complete remission [CR], partial remission [PR], or hematologic improvement [HI]) (Gore et al, Haematologica, 2013). However, it is not well established if pts who achieve SD by 6 months (mo) of therapy should be offered different therapies to optimize their response or continue with the same HMA regimen. Methods Clinical data were obtained from the MDS Clinical Research Consortium database. Pts treated with either AZA or decitabine (DAC) were included and categorized per the Revised International Prognostic Scoring System. Responses were evaluated per International Working Group (IWG 2006) criteria. SD was defined as no evidence of progression and without achievement of HI. Early response was defined as achievement of CR, PR, HI, or SD between 3-6 months (mo) of therapy. Best response was assessed after 6 mo of treatment. OS was calculated from the start of therapy to date of death or last follow up. Differences were evaluated using the Fisher-exact test and Mann-Whitney U tests for categorical and continuous variables, respectively. Results Of 291 pts with higher-risk MDS and available response data, 248 (85%) received treatment with AZA and 43 (15%) with DAC. Median age was 70 years (range, 35-99), median absolute neutrophil count (ANC) was 1.05 X109/L (range, .58-68), hemoglobin 9.3 g/dL (range, 3.7-14.3), platelets 73 X109/L (range, 4-659), and bone marrow blasts 10% (range, 0-19). Per IPSS-R, 20% of pts were intermediate risk, 37% high, and 43% very high. A total of 142 pts (49%) progressed to AML. Median time from diagnosis to start of HMA was 28 days. Early responses (3-6 mo) were: CR 10%, PR 5%, HI 10%, and SD 49%. Among the 144 pts who achieved SD at 3-6 mo, 29 (20%) achieved a better response (CR, PR, or HI) later during their treatment, with a median time to better response of 3.7 mo (range,1.2-14.5); 113 (89%) remained with stable disease, and 2 (1%) progressed to AML. With a median follow up of 16.5 mo (range, 2.5-120.2), the median OS by best response at any time point during therapy: CR 19.7 mo, PR 12.6 mo, HI 15.4 mo, and SD 13.8 mo. Pts who achieved CR had superior OS compared to SD (p=.03) but similar survival compared to pts who achieved PR (p=.45) or HI (p=.24). Of 29 pts with SD who achieved a better response > 6 mo, 16 (55%) achieved a CR and 13 (45%) achieved a PR or HI. Pts with SD who subsequently achieved CR had superior OS compared to pts who remained in SD (28.1 vs 14.4 mo, respectively, p=.04), while pts who subsequently achieved PR or HI had a similar survival compared to pts who remained in SD (12.1 vs 14.4 mo, respectively, p=.81). Conclusion Among MDS pts treated with HMAs, 20% who have SD at initial assessment go on to have a better response later in their treatment course, However, only 11% of SD pts achieved a CR thereafter, which predicted better OS. Thus, pts who achieve SD by 6 mo should be offered a clinical trial with novel agents to improve their chances of achieving CR. If a clinical trial is not available, pts should remain on HMA therapy until disease progression. Disclosures No relevant conflicts of interest to declare.

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A Case of Duodenal Neuroendocrine Carcinoma Treated with Amrubicin as Second-line Chemotherapy

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.243.ino ◽

2015 ◽

Vol 24 (3) ◽

pp. 379-382

Author(s):

Tadahisa Inoue ◽

Hitoshi Sano ◽

Takashi Mizushima ◽

Hirotada Nishie ◽

Hiroyasu Iwasaki ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Distant Metastases ◽

Salvage Chemotherapy ◽

Second Line ◽

Effective Treatment Option ◽

Second Line Chemotherapy ◽

Best Response ◽

Long Term Effect ◽

Line Chemotherapy

We present the case of a Japanese man in his 60s with duodenal neuroendocrine carcinoma with distant metastases. Chemotherapy with irinotecan plus cisplatin was initiated as a first-line regimen. However, disease progression was observed after only two cycles. Therefore, amrubicin was administered as a second-line chemotherapy. The patient showed a long-term effect of amrubicin therapy, and the best response was a partial response after seven cycles. For duodenal neuroendocrine carcinoma, amrubicin therapy can be considered an effective treatment option as salvage chemotherapy.

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Re-use of erlotinib in a patient using osimertinib after erlotinib, case report

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211019108 ◽

2021 ◽

pp. 107815522110191

Author(s):

Pinar Gursoy

Keyword(s):

Lung Cancer ◽

Case Report ◽

Treatment Options ◽

Resistance Mutation ◽

Growth Factor Receptor ◽

Complete Response ◽

Egfr Mutations ◽

T790m Mutation ◽

Development Of Resistance ◽

Exon 19

Introduction Most patients with non-small-cell lung cancer tumors that have epidermal growth factor receptor (EGFR) mutations have deletion mutations in exon 19 or exon 21, or both.In recent years, targeted therapies in lung cancer have increased survival, but the development of resistance to these drugs poses a major problem. Thesubstitution of methionineforthreonine at position 790 (T790M) mutation,is primarily responsible for this resistance. However, after osimertinib used in T790M positivepatients treatment options are generally limited to chemotherapy. Case report We reported the efficacy of erlotinib, which we reapplied due to the disappearance of the resistance mutation after osimertinib in a 68-year-old patient using osimertinib after erlotinib. Management and outcome: In the patient using erlotinib due to exon 19 deletion when progression was observed and T790M positivity was detected, osimertinib treatment was initiated. However, when T790M was found to be negative with rebiopsy in progression after osimertinib, a complete response was achieved by restarting erlotinib. Discussion The strategy of restarting erlotinib treatment with negative T790M mutation detected in biopsies of patients with osimertinib resistance may be an acceptable treatment option.

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