Efficacy and Safety of Gemtuzumab-Based Regimens in Patients with CD33-Positive Refractory Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4358-4358
Author(s):  
Suijing Wu ◽  
Xin Du ◽  
Wei Lin ◽  
Jianyu Weng ◽  
Jianjun Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Survival Time ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Response Rate ◽  
Single Agent ◽  
Efficacy And Safety ◽  
Blast Phase ◽  
Median Overall Survival Time

Abstract Patients with relapsed or refractory leukemia have less chances of obtaining remission than patients with newly diagnosed.It is reported that more than 80% of acute myeloid leukemia(AML) patients have myeloid blast cells that express the CD33 surface antigen. This antigen also is present on the leukemic stem cells at least some patients with chronic myeloid leukemia(CML)and acute lymphoblastic leukemia(ALL). It is absent from normal hematopoietic stem cells and nonhematopoietic cells and tissues. Gemtuzumab is a humanized anti-CD33 antibody conjugated to calicheamicin, a potent anti tumor antibiotic derived from a bacterium. It is conditionally approved in the US for treatment of CD33+ AML in first relapse in patients over 60 years[Sievers et al.Journal of Clinical Oncology,2001]. Here we evaluate the efficacy and safety of Gemtuzumab -based regimens. The study population comprise 11 patients with CD33-positive refractory leukemia (determined as CD33-antigen expression in over 50% of leukemic blasts by bone marrow aspirates and immunophenotyping), including two with myeloid blast phase of CML, one with refractory ALL, two relapsed after Auto-stem cell transplantation(Auto-SCT). The median age was 47 years. Four cases who were over 60 years or after Auto-SCT treated with single agent. The other seven cases treated with mylotarg and cytotoxic agents, including mylotarg plus idarubine (MI); Gemtuzumab plus fludarabine, cytarabine, CsA(MFAC); or plus mitoxantrone, Ara-C (MMA).The overall response rate was 54% (6/11), with 36%(4/11) patients obtaining complete remission (CR) and 18% (2/11) achieving CRp.The median overall survival time after treatment was 4.8 months, and the median overall survival time after CR was 8.2 months.Two patients with myeloid blast phase of CML achieved CR with BCR/ABL(−), the survival time after CR was 5+months and 20+months respectively, but failed in second relapse. One patient received Allo-SCT after CR with refractory ALL is still alive at present (21months) with disease free. The median time to ANC recovery of 0.5×109/L was 15 days.The common adverse events was myelosuppression (100% Grade 4 neutropenia and thrombocytopenia).Significant non-hematologic toxicitics included infection(96%), infusion-related chills and fever (55%).Although hepatic dysfunction and mucositis were observed,they were generally infrequent and not severe(Grade 1–2).Six patients (55%) developed Hepatic veno-occlusive disease(VOD), four of them were either over 60 years old or received Auto-SCT before although they received only single agent mylotarg therapy, but it was transient and no one died from it. In conclusion, patients with CD33-positive refractory leukemia, Gemtuzumab -based regimens have a comparable response rate and offer a more favorable toxicity profile, expecially for the patients with myeloid blast phase of CML. It is also effective for the patient with refractory ALL. In the treatment, we should pay attention to the hepatic condition of ones who are over 60 years old or after stem cell transplantation, attemps to avoid and treat VOD are warranted. Above all, When patients with refractory leukemia got remission, allogenic-SCT should be done as soon as possible

Modified Topotecan Combination with Cyclophosphamide and Ara-C (CAT) for Patients with Refractory/Relapsed Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4357-4357
Author(s):  
Sui-jing Wu ◽  
Xin Du ◽  
Wei Lin ◽  
Zi-lun Huang ◽  
Xiao-li Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Survival Time ◽  
Median Time ◽  
Topoisomerase I ◽  
Median Overall Survival ◽  
Blast Phase ◽  
Platelet Recovery ◽  
Overall Survival Time ◽  
Median Overall Survival Time

Abstract The prognosis of patients with leukemia has improved significantly. With combination chemotherapy, 60%–80% of adult patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia(ALL) achieve complete remission(CR). But most patients eventually relapse and do not response to current induction regimens based on cytarabine and anthracyclines any more. This emphasize the need to discover new agents for the treatment of leukemia to improve long-term prognosis. Topotecan is a semisynthetic analogue of the alkaloid camptothecin which acts as a specific inhibitor of topoisomerase I,by stabilization of the topoisomerase I DNA complex which leads to cell death.It also appears to be active against leukemias which have acquired the multi-drug resistant phenotype.[ Ulukan et al. Drug, 2000; Weihrauch et al. Leuk Lymphoma, 2004].It also could go through blood brain barrier[Kollmannsberger et al. Oncology, 1999].Here we observe the effect and side-effects of cyclophosphamide, cytanthetic analogue of rabine and topotecan (Modified CAT) combination regimen for treatment of refractory or relapsed leukemia. The study population comprise 26 patients with relapsed/refractory leukemia,including 12 with AML, 9 with ALL, 2 with myeloid blast phase of CML, 3 with lymphoma. Median age was 35 years.Patients received cyclophosphamide 300mg/m2 every 12 hours for 6 doses on day1 to 3.On day 2, topotecan was given at a dose of 1.5mg/m2/day for 5 days on days 2 to 6, and cytarabine 1.0 g/m2 /day for 5 days on days 2 to 6.The regimen (cytarabine reduced to 0.5g/m2 /day) could be repeated one or two cycles after remission. The total response rate of one course was 57%, eleven patients (42%) achived complete remission(CR). Responses occurred in 7of 12 AML (57%), including 5 CR(41%); in 6 of 9 patients with ALL (67%), including 5 CR(56%); and in 1 of 2 myeloid blast phase of CML(CR 50%). The median overall survival time after treatment was 2+ months, and the median overall survival time after CR was 4+ months. Severe myelosuppression was universal (100% Grade 4 neutropenia and thrombocytopenia), the median time to recovery of neutrophils to ≥0.5×109/L was 18 days,and the median time to platelet recovery to ≥ 20×109/L was 26 days.Infection developed in 96% cases, the most frequent events were oral mucositis(77%, 20/26), sepedogenesis(46%, 12/26),anusitis(38%,10/26),pneumonia(31%, 8/26), two patients died of infection complications(8%). Non-hematologic toxicity was seen frequently in gastrointestinal but it was mild. Nausea and/or vomiting occurred in 13 patients(50%)with gradeI-II in all of them.Two patients(8%) had diarrhea and grade 1–2 in them. In summary, Modified CAT regimen is well tolerated and has significant anti-leukemia activity as salvage therapy for relapsed/refractory leukemia.

scholarly journals Efficacy and Safety of Selinexor for Acute Myeloid Leukemia: A Systematic Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Mydah Sajid Hashmi ◽  
Muhammad Ans Sharif ◽  
Ali Jaan ◽  
Umer Salman ◽  
Summera Aziz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Response Rate ◽  
Single Agent ◽  
Efficacy And Safety ◽  
Event Free Survival ◽  
Free Survival ◽  
Combination Regimens

Introduction: Selinexor, an exportin 1(XPO1) inhibitor has demonstrated anti-leukemia activity as a single agent, as well as in combination regimens for the treatment of acute myeloid leukemia (AML). This systematic review aims to explore the efficacy and safety of selinexor based regimens for the treatment of AML. Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane library, ClinicalTrials.gov, ASCO, and ASH meeting websites. The initial databases yielded 698 articles (last updated search until July 20, 2020). After excluding review articles, duplicates, and non-relevant articles, we included data from eight clinical trials (Table 1 and Table 2). Results: Among a total of 286 patients, 259 were evaluated. Selinexor was given as monotherapy to 81 patients and as combination regimens to 178 patients. The total newly diagnosed (ND) AML patients were 48 and relapsed refractory (RR) AML patients were 238. Garzon et al. did a phase I dose-escalation trial (n=81) with selinexor as a single agent in ND-AML and RR-AML patients with a median of three prior lines of therapy. The overall response rate (ORR) was 14%. The median overall survival (OS) was 2.7 months and median progression-free survival (PFS) was 1.7 months. 15% of the patients discontinued the treatment temporarily due to adverse events (AEs). Bhatnagar et al. (n=25) studied selinexor with decitabine, in phase I clinical trial, in ND and RR-AML patients. The ORR was 40% with higher ORR in ND-AML (80%) compared to RR-AML (30%). At a median follow-up of 21.8 months, the median PFS was 5.9 months (95% CI: 2.4-8.7) and median OS was also 5.9 months (95% CI: 3.9-10.4). The PFS was longer for patients who responded to therapy (11.8 months) as compared to those who did not respond to therapy (4.4 months). In phase I/II trial by Daver et al. (n=14) with selinexor and sorafenib in RR-AML patients, the composite complete remission including CR, CR with incomplete blood count recovery (Cri), and CR with incomplete platelet recovery (CRp) was 35.7%. The event-free survival was 1.8 months (0.4-5.0) in FLT3-ITD Inhibitor failure cohort vs 2.1 months (0.7-2.1) in FLT3-ITD inhibitor naive cohort. A single-arm phase I study with selinexor, cytarabine, and daunorubicin was performed testing ND-AML patients by Sweet et al., (n=19). It showed an ORR of 53% and a median OS of 10.3 months (95% CI: 3.74-NR). The early death rate (death ≤ 60 days) was 4.8%. The phase I dose-escalation trial by Weng et al. (n=28) in ND and RR-AML patients with selinexor+cytarabine+mitoxantrone had a better response rate. The ORR was 64% with a higher ORR in ND-AML (87%) compared to RR-AML (38%). The phase I trial by Alexander et al. (n=18) with selinexor+ cytarabine+ fludarabine on RR-AML patients achieved an ORR of 60 % and CR of 33.3%. Fielder et al. (n=38) did a phase II clinical trial on RR-AML patients with selinexor+ cytarabine + idarubicin with 40 mg/m2 selinexor in one cohort (C1) and flat 60 mg dose of selinexor in the second cohort (C2). In C1 37% of patients and C2 40% of patients had previous stem cell transplantation (SCT). The ORR was almost the same in both cohorts, with 55 % in C1 vs 54.5% in C2. The phase I/II trial on RR-AML patients by Abboud et al. (n=40) with selinexor+ cladribine+cytarabine+filgrastim had a total of CR and CRi in 45% of patients with a median overall survival of 7.8 months (95%CI: 5.7-14.1) and median event-free survival of 6.1 months (95% CI: 4.5 - 7.8 months). The main hematological adverse events were pancytopenia and non-hematological adverse events were hypophosphatemia, hyponatremia, gastrointestinal disturbances, and fatigue (Table 2). Conclusion: Selinexor in combination regimens showed superior response rates compared to selinexor alone for the treatment of AML patients. The response rates were better in selinexor based three and four-drug regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15678-e15678
Author(s):  
Beom Kyung Kim ◽  
Do Young Kim ◽  
Hye Jin Choi ◽  
Seung-Hoon Beom ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Sorafenib Treatment

e15678 Background: Patients with advanced hepatocellular carcinoma (HCC) have a particularly poor prognosis of the median overall survival of less than 12 months. Even though sorafenib has been approved for treating advanced stage HCC, the unsatisfactory objective response rate still remain unresolved. In the current study, we aimed to evaluate the efficacy and safety of localized concurrent chemoradiotherapy (CCRT) followed by sequential sorafenib treatment for advanced hepatocellular carcinoma. Methods: This study is an ongoing, phase II trial. Patients with advanced HCC not amenable for curative treatments were eligible. In the course of radiotherapy for 5 weeks, hepatic arterial infusion of 5-fluorouracil (500mg/day) via implanted port was applied during the first 5 days and the last 5 days of radiotherapy. Four weeks after localized CCRT, sorafenib (400mg bid) was maintained. The primary endpoint was overall survival. Results: A total of 47 patients were enrolled. After the completion of localized CCRT, the objective response rate was 31.9%. During the overall treatment course, the objective response rate was 46.8% respectively. Overall, 7 patients (14.9%) underwent curative resection or transplantation after down-staging. The median overall survival was 18.4 months and the progression-free survival was 6.8 months. Adverse events were predictable and manageable with conservative care. Conclusions: Localized CCRT followed by sequential sorafenib treatment in patients with advanced HCC showed significant activity and good tolerability. Furthermore, such a treatment modality, when compared to the use of sorafenib alone, might provide the additional therapeutic benefit through initial tumor reduction, allowing curative treatment after down-staging in 14.9% of patients, Further randomized trial should be required to make the more robust evidence. Clinical trial information: NCT02425605.

Caspase 3 Expression in Mantle Cell Lymphoma: An Immunohistochemical Study of 84 Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4676-4676
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Paul Riis ◽  
Peter Meusers ◽  
Guenter Brittinger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Median Overall Survival ◽  
Caspase 3 ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
Overall Survival Time ◽  
Mantle Cell ◽  
Median Overall Survival Time

Abstract Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3–4 years. We investigated immunohistochemically the expression of the apoptotic marker caspase 3 in relation to the clinical course. Biopsy specimen from 84 untreated patients enrolled in two multicenter prospective trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, Caspase3. The Caspase3 expression was analyzed in three groups: less than 1 positive cell per high power field (HPF), more than 1 positive cell per HPF and more than 2 positive cells per HPF. The expression was compared with the overall survival data analysed according to Kaplan and Meier. In 75 cases the caspase 3 staining could be analyzed. The caspase 3 expression had a range of 0.1–4.7 positive cells per HPF (median value:1.1, mean:1.3). Patients with mantle cell lymphoma that had less than 1 caspase 3 positive cell per HPF (33 cases) had a median overall survival time of 48 months compared to 27 months for patients with more than 1 positive cell per HPF (24 cases) and 15 months for more than 2 positive cells per HPF (18). The Kaplan-Meier analysis showed a significant difference in the overall survival time between these groups (p<0.0001). The immunohistochemical detection of caspase 3 in mantle cell lymphoma is a predictor for survival in MCL.

Apoptosis Regulating Proteins bax and p53 in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4710-4710
Author(s):  
Carsten Schrader ◽  
Wolfram Klapper ◽  
Dirk Janssen ◽  
Paul Riis ◽  
Peter Meusers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Mantle Cell Lymphoma ◽  
Survival Time ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
P53 Expression ◽  
Overall Survival Time ◽  
Mantle Cell ◽  
Median Overall Survival Time

Abstract In malignant tumors beside cell proliferation also cell death plays role for cell survival. Apoptosis regulating genes can be divided into two groups: death antagonists and death agonists such as bax. The ratio of death agonists and antagonists determines if a cell goes into apoptosis. We investigated in a large collective the immunohistochemical expression of the apoptotic marker p53 and bax in relation to the clinical course. Biopsies were stained immunohistochemically with monoclonal antibodies against bax and p53 and the expression was subdivided in three groups: negative, weak positive and strong positive. The expression profiles were analyzed with the overall survival data according to Kaplan and Meier. Patients with mantle cell lymphoma that had negative p53 expression had a median overall survival time of 38.1 months compared to 22.3 months for patients with a weak and 11.3 months for a strong p53 expression (0<0.0001). The bax expression was in the majority of cases positive. Only one case showed a negative staining. Patients with weak and strong bax expression showed no differences in clinical outcome (median overall survival time: 23 vs 33 months, p=0.6051). The immunohistochemical detection of p53 in mantle cell lymphoma is a good predictor for the clinical outcome.

Phase II Trial of Trastuzumab Followed by Weekly Paclitaxel/Carboplatin As First-Line Treatment for Patients With Metastatic Breast Cancer

2004 ◽  
Vol 22 (9) ◽  
pp. 1621-1629 ◽  
Author(s):  
Howard Burris ◽  
Denise Yardley ◽  
Suzanne Jones ◽  
Gerry Houston ◽  
Catherine Broome ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Median Time ◽  
Median Overall Survival ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Weekly Paclitaxel ◽  
Time To Progression

Purpose To determine the response rate of trastuzumab as first-line therapy in patients with HER-2 overexpressing metastatic breast cancer. To assess the feasibility and toxicity of weekly paclitaxel/carboplatin with or without trastuzumab following initial treatment with trastuzumab. Patients and Methods Sixty-one patients received trastuzumab (8 mg/kg followed by 4 mg/kg/wk) for 8 weeks. Responding patients received 8 additional weeks of trastuzumab (4 mg/kg/wk), and then proceeded to receive trastuzumab (2 mg/kg) in combination with paclitaxel 70 mg/m2 and carboplatin (area under the curve, 2) weekly for 6 weeks followed by 2 weeks rest. Stable patients after the initial 8 weeks of trastuzumab proceeded to treatment with trastuzumab, paclitaxel, and carboplatin. Patients with disease progression during the initial 8 weeks had the trastuzumab discontinued and were treated with weekly paclitaxel/carboplatin. Results Weekly paclitaxel/carboplatin with or without trastuzumab was well tolerated. Fifty-two patients were assessable for response and all 61 patients were assessable for survival. Seventeen (33%) of 52 patients experienced a minor/partial response to single-agent trastuzumab and received 8 additional weeks of single-agent trastuzumab. Fifteen (29%) of 52 patients had stable disease and proceeded to receive paclitaxel/carboplatin/trastuzumab. Thirty-one patients with measurable disease were assessable for response after initial single-agent trastuzumab followed by paclitaxel/carboplatin/trastuzumab. An overall response rate of 84% (eight complete responses/18 partial responses), median time to progression of 14.2 months, and median overall survival of 32.2 months was reported with the triplet combination. In the patients treated with paclitaxel/carboplatin alone after disease progression on initial single-agent trastuzumab, an overall response rate of 69% (one complete response/10 partial responses), median time to progression of 8.3 months, and median overall survival of 22.2 months was reported. Median time to progression for all 61 patients is 10 months and the median overall survival is 26.7 months. Conclusion This trial confirms the activity and tolerability of weekly paclitaxel/carboplatin alone or in combination with trastuzumab in women with HER-2 overexpressing metastatic breast cancer.

Clofarabine in Children with Refractory/Relapsed Acute Leukemia: Results of 2 Phase II Open Label Studies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4460-4460
Author(s):  
Sima Jeha ◽  
Bassem Razzouk ◽  
Paul Gaynon ◽  
Michael Rytting ◽  
Richard Kadota ◽  
...  
Keyword(s):  
Overall Survival ◽  
Febrile Neutropenia ◽  
Acute Leukemia ◽  
Median Overall Survival ◽  
Response Rate ◽  
Single Agent ◽  
Significant Activity ◽  
Induction Regimen ◽  
Heavily Pretreated

Abstract Background: Clofarabine is a second generation purine nucleoside analogue synthesized to improve the properties of its congeners, fludarabine and cladribine. Clofarabine inhibits DNA polymerase alpha and ribonucleotide reductase, leading to the depletion of intracellular deoxynucleotide triphosphate pools, disruption of mitochondrial function and apoptosis. Methods: Clofarabine was administered by IV infusion over 2 hrs for 5 days at 52 mg/m2/day and repeated every 2–6 weeks based on bone marrow response and recovery of normal hematopoiesis. An independent review panel confirmed all results. Results: The median age of the 103 children (61 with ALL and 42 with AML) was 12 years (range 1–22 yrs). ALL: The overall remission rate (CR+CRp) was 20%; 30% (18/61) of patients showed a response (7CR, 5CRp, 6PR). Responses were noted in 15 of 50 (30%) patients with B- lineage ALL, 2 of 6 (33%) with T-cell ALL. Responders received a median of 3 prior induction regimens; 50% (9/18) had prior HSCT and 50% (9/18) were refractory to the preceding induction regimen. Response rate in refractory patients was 26% (9/35). After clofarabine treatment, 10 patients proceeded to transplant (including 8 responders). 6 of 10 patients who received a transplant were alive at last follow up (survival range: 30.1+ – 145.1+ wks). Response duration in 6 patients with CR or CRp who did not receive a transplant ranged from 4.3 to 58.6 weeks; 2 patients maintained CR for 47.9 and 58.6 weeks after clofarabine therapy. Median overall survival for the patients who achieved at least a PR was 66.6 weeks compared to 12.9 weeks for all patients. AML: The response rate for AML patients was 26% (1 CRp, 10 PR). Responders had received a median of 2 prior induction regimens, 36% (4/11) had prior HSCT and 55% (6/11) patients were refractory to the preceding induction regimen. Response rate in refractory patients was 21% (6/28). One patient who had received 5 prior induction regimens achieved CRp. 13 (31%) patients (1CRp, 6PR, 3NE, 3TF) underwent HSCT after completing clofarabine therapy, 5 of whom were alive at last follow-up (survival range: 62.7+ – 160.1+ wks). Many patients proceeded to HSCT as soon as a donor was identified without waiting for the patient to go into remission, making remission difficult to assess. Median overall survival for patients who achieved at least a PR was 32.1 wks compared to 23.4 wks for all patients. Safety: The side effect profile was not unexpected in this heavily pretreated population. The ≥ gr 3 drug related AEs occurring in ≥10% patients included febrile neutropenia for ALL patients; febrile neutropenia, pyrexia, nausea, neutropenia, and hypotension for AML patients. Conclusion: Clofarabine shows significant activity in heavily pretreated children with multiply relapsed acute leukemia, allowing otherwise refractory patients to proceed to HSCT. Durable responses were seen in ALL patients with no donor options who continued therapy with single agent clofarabine. Combination studies incorporating clofarabine in pediatric patients with relapsed ALL and AML are ongoing.

Subcutaneous Alemtuzumab (MabCampath) in Fludarabine-Refractory CLL (CLL2H Trial of the GCLLSG).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3120-3120 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Dirk Winkler ◽  
Andreas Bühler ◽  
Thorsten Zenz ◽  
Silja Groner ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Survival Time ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Outpatient Basis ◽  
Free Survival ◽  
Overall Survival Time ◽  
Median Overall Survival Time ◽  
Grade Iii

Abstract Fludarabine-refractory CLL has a poor prognosis with a median overall survival time of less than 12 months despite salvage chemotherapy and intravenous alemtuzumab (Campath-1H) is the approved treatment based on a remission rate of 33% and a median survival time of 16 months (Keating et al., Blood 2002). The CLL2H trial of the GCLLSG was initiated to evaluate the subcutaneous application of 3 × 30 mg alemtuzumab weekly in fludarabine refractory CLL. The current analysis is based on 109 consecutive patients enrolled until completion of the trial in April 2006. Median age was 63 (36–81) years, 71% were male. A median number of 3 (1–9) prior lines of therapy had been given. Subcutaneous treatment was performed on an outpatient basis in all cases and had to be temporarily interrupted in 68 patients due to neutropenia (43%), anemia (6%), thrombocytopenia (3%), infections (40%, CMV reactivations 30%), and was stopped early in 63 cases due to insufficient response (44%), hematotoxicity (16%), infection (17%), and CMV reactivation (13%). The median alemtuzumab dose given was 722 (3–2203) mg. Toxicity was mostly grade I/II apart from hematotoxicity (grade III/IV anemia: 42%, thrombocytopenia: 52%, neutropenia: 54%) and grade III/IV infections (25%). After a median follow up time of 21.4 months, 56 deaths have occurred (due to progression 52%, infections 39%, not CLL related 9%). The overall response rate was 33% (CR 4%, PR 27%), the median progression free survival time was 7.7 months, and median overall survival time was 19.1 months. Genetic high-risk factors were present in the vast majority of cases (unmutated VH 66%, 17p–29%, 11q–19%, TP53 mutation 39%). Responses (CR or PR) were observed in 22% of VH unmutated, 24% of 11q-, 39% of 17p-, and 33% of TP53 mutated cases. Progression free survival and overall survival were not significantly different when comparing the genetic subgroups, particularly TP53 mutated, 11q-, and 17p- (see figure). In conclusion, subcutaneous alemtuzumab is feasible in an outpatient setting in a high-risk population of fludarabine-refractory CLL and appears to be of similar efficacy as by intravenous administration. Most importantly, genetic high risk subgroups with unmutated VH, 11q- or 17p- appear to respond to alemtuzumab. Figure Figure

SOX11 Expression Versus Indolent Clinical Course in Mantle Cell Lymphomas in a Population-Based Cohort From the Stockholm Region – SOX11 Negative Tumors Are Mostly p53 Positive, Contributing to Shorter Overall Survival,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3651-3651
Author(s):  
Birgitta Sander ◽  
Monika Klimkowska ◽  
Lina Nygren ◽  
Stefanie Baumgartner ◽  
Birger Christensson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cyclin D1 ◽  
Survival Time ◽  
Median Overall Survival ◽  
Clinical Course ◽  
Population Based ◽  
Mantle Cell ◽  
Sox11 Expression ◽  
Indolent Disease ◽  
Median Overall Survival Time

Abstract Abstract 3651 Introduction: Mantle cell lymphoma (MCL) constitutes 3–10% of non-Hodgkin lymphomas and has a median survival of 3–5 years. A small number of patients are characterized by a clinically indolent disease and may not require treatment for several years. However, these are difficult to identify at the time of diagnosis due to lack of reliable predictive markers. Recently, the nuclear expression of the transcription factor SOX11 has been suggested to be of prognostic value in MCL. Materials and Methods: All 186 patients diagnosed with MCL in the Stockholm region between January 1998 and June 2010 were included. Diagnosis was according to the WHO criteria and all cases were cyclin D1 positive by IHC and/or for t(11;14) by FISH. Clinical data from patient files, diagnostic biopsies and flow cytometry data were reviewed. Patients not requiring treatment within the first two years after diagnosis were retrospectively defined as indolent disease. Patients were further categorized in nuclear SOX11 negative (n=13) and nuclear SOX11 positive (n=160) cases and in cases with indolent (n=17) versus non-indolent disease course (n=169). The following variables were evaluated at the time of diagnosis: age, sex, Ann Arbor stage, ECOG, B-symptoms, Hb, LDH, albumin, lymphocytosis, leukocytosis, splenomegaly, nodal and bone marrow involvement, MIPI, indolent disease, blastoid morphology, expression of CD23, light chain, Ki 67, SOX11 and p53. Overall survival was analyzed, excluding patients receiving ASCT (n=37). Baumgartner, S. et al presents further data on the entire cohort in the accompanying abstract. Results: The following variables were significantly more common in SOX11 negative cases (Table 1): Lymphocytosis (p=0,045), high LDH (p=0,029) and p53 positivity (p<0,000). MIPI high risk was more frequent among SOX11 negative patients but did not reach statistical difference. There were no statistically significant differences in the frequency of splenomegaly or indolent disease among SOX11 negative and positive cases. Median overall survival time was 36,7 months in the whole cohort; 16,5 months in patients with SOX11 negative tumors and 39,3 months in patients with SOX11 positive tumors (p=0,015), excluding 37 patients (1 SOX11 negative, 38 SOX11 positive) receiving ASCT as part of first-line therapy. Patients with an indolent clinical course had significantly less often B symptoms (p=0,002), nodal presentation (p=0,019) and elevated LDH (p=0,040) than patients with a non-indolent disease, while none of the other factors analyzed reached statistical significance. Median overall survival time of patients with indolent disease was not reached (median follow-up time 41,7 months). 15/17 of the MCL cases with indolent clinical course expressed SOX11. Conclusions: In a population-based cohort of 186 cyclin D1 positive MCL, 8% lacked expression of nuclear SOX11 at diagnosis. There was no enrichment of patients with an indolent disease among SOX11 negative MCL. Instead patients with SOX11 negative MCL had a higher frequency of lymphocytosis and elevated LDH at diagnosis and a shorter overall survival. MCL lacking nuclear SOX11 expression at diagnosis were more frequently p53 positive which may contribute to shorter survival in the SOX11 negative MCL subset. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Apatinib Combined With S-1 in the Treatment of Advanced Gastric Cancer: a Meta-analysis

2021 ◽  
Author(s):  
Xu Zhang ◽  
Xiao-dong He ◽  
You-cheng Zhang ◽  
Ke-hu Yang ◽  
Jin-hui Tian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Adverse Reactions ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Efficacy And Safety

Abstract Objective: To study the efficacy and safety of apatinib combined with S – 1 in the treatment of advanced gastric cancer, in order to provide more evidence based medical evidence for the clinic.Methods: Randomized controlled trials of apatinib combined with S – 1 (experimental group) versus S - 1 (controlg roup) in the treatment of advanced gastric cancer were collected by computer literature search in Chinese and English databases, for the deadlines of March 21, 2021. Two investigators independently screened the literature, extracted the data, and evaluated the quality of the literature using the Cochrane risk bias assessment tool. And the Meta – analysis was performed using Review Manager 5. 3 software almost.Results: A total of 20 articles were included, totaling 1,150 patients. Meta – analysis showed that the objective response rate [OR = 2.02, 95% CI (1.56, 2.63), P < 0.00001], disease control rate [OR = 3.10, 95% CI (2.30, 4.17), P < 0.00001], median overall survival [MD = 3.99, 95% CI (3.56, 4.43), P < 0.00001] of patients with apatinib combined with S – 1 group were higher than the S – 1 group, then the median progression – free survival had not significant differences [MD = 1.24, 95% CI (-1.19, 3.67), P = 0.32]. In the adverse reactions, only the incidence of hypertension [OR = 6.19, 95% CI (1.89, 20.23), P = 0.003] and the incidence of proteinuria [OR = 4.02, 95% CI (1.11, 14.62), P = 0.03] in the apatinib combined with S – 1 group were higher than the S – 1 group, and there was no significant difference in the other adverse reactions. In addition, the levels of IFN – γ and TNF – α in the apatinib combined with S – 1 group were higher than those in the S – 1 group, and the levels of IL - 10, IL – 4, TSGF, CA199 and CEA were lower than those of the S – 1 group.Conclusion: Current evidence suggests that apatinib combined with S - 1 can achieve higher objective response rate, disease control rate, median overall survival, less adverse reactions, and improve immune function, effectively reduce the level of tumor markers.

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