Low dose IL-2 in patients with steroid-dependent dysimmune manifestations associated with myelodysplastic syndromes: a three-case report

Rheumatology ◽  
2020 ◽  
Author(s):  
Marion Corfmat ◽  
Christophe Willekens ◽  
Julien Vinit ◽  
Guillaume Bussone ◽  
Pierre Fenaux ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myelodysplastic Syndromes ◽  
Low Dose ◽  
Response Rate ◽  
Immunosuppressive Agents ◽  
Relapsing Polychondritis ◽  
Joint Involvement ◽  
Immune Disorders ◽  
Serious Adverse Events ◽  
Steroid Dependent

Abstract Objectives Systemic inflammatory and autoimmune diseases can be associated with myelodysplastic syndromes. Current treatments (steroids, immunosuppressive agents, biologics) are unsatisfactory because of their low response rate, dependence or adverse events. We aimed at evaluating the effects of low doses of IL-2 (ld-IL2) as a regulatory T-cell inducer in this context. Methods We treated three patients with ld-IL2 with myelodysplastic syndromes and an associated dysimmune disorder (polymyalgia rheumatic, relapsing polychondritis associated with Sweet’s syndrome and vasculitis with cutaneous and joint involvement, respectively). All three patients were dependent on steroids and refractory to biologics or azacitidine. They received doses of 1–1.5 million units of proleukin/day during 5 days and then every fortnight. Results The treatment led to a clinical improvement and steroid sparing in 2/3 patients with no serious adverse events, and no progression of the disease. Conclusion Our results support the investigation of ld-IL2 in MDS associated with immune disorders in controlled clinical studies.

scholarly journals Efficacy of Lenalidomide plus Low-Dose Dexamethasone in Thai Patients with Relapsed and/or Refractory Multiple Myeloma

2021 ◽  
Vol 73 (5) ◽  
Author(s):  
Chutima Kunacheewa ◽  
Noppadol Siritanaratkul
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Serious Adverse Events ◽  
Refractory Multiple Myeloma ◽  
Overall Response ◽  
Depth Of Response

Objective: Lenalidomide is an immunomodulatory agent with proven efficacy in the treatment of multiple myeloma. In large global clinical studies, lenalidomide plus dexamethasone has demonstrated significant improvements in the overall response rate and overall survival in patients with relapsed and/or refractory multiple myeloma, compared with a placebo and dexamethasone. This is the first study to report lenalidomide plus low-dose dexamethasone administered in Thai patients. Methods: The aim of this phase II, single-center, single-arm study was to evaluate the efficacy and safety of lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma. The primary endpoint was the overall response rate at the fourth treatment cycle. Secondary endpoints included depth of response, time to response, and adverse events. Results: In total, 15 patients with a median age of 61 years old (range 23–74 years old) who had received at least one prior anti-myeloma therapy were enrolled in the study and administered 4-week cycles of lenalidomide 25 mg/day (days 1–21) and dexamethasone 40 mg/week. Patients continued in the study until the occurrence of disease progression or serious adverse events. The overall response rate was 86% and 73.3% at the fourth and from all treatment cycles, respectively (median number of treatment cycles, 10.25), and the median dose for patients aged >60 years old was 15 mg/day. The overall response rate at the fourth cycle in patients who had received prior novel agents (bortezomib and/or thalidomide) was 81.82% compared with 100% in those who had received prior conventional therapy (p = 0.15). The most common adverse events reported were anemia and neutropenia, which were both manageable. Conclusion: Lenalidomide and low-dose dexamethasone was highly effective in Thai patients with relapsed and/or refractory multiple myeloma, with a manageable adverse event profile. These findings suggest that lenalidomide 15 mg/day is a safe and effective dose for Thai patients aged ≥60 years old.

scholarly journals AB1335-HPR HEALTH PROFESSIONALS’ PERSPECTIVE ON THE BENEFITS AND RISKS OF LOW-DOSE GLUCOCORTICOIDS IN RHEUMATOID ARTHRITIS – AN INTERNATIONAL SURVEY OF 444 HEALTH PROFESSIONALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1955.1-1956
Author(s):  
T. Santiago ◽  
M. Voshaar ◽  
M. De Wit ◽  
P. Carvalho ◽  
M. Boers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Professionals ◽  
Patient Perspective ◽  
Online Survey ◽  
Low Dose ◽  
Low Doses ◽  
Research Support ◽  
Serious Adverse Events ◽  
Patient Organizations

Background:The Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis Study (GLORIA) is an international investigator-initiated pragmatic randomized trial designed to study the effects of low-dose glucocorticoids (GCs) in elderly patients with Rheumatoid Arthritis (RA).The research team is also committed to promote a better understanding of the risks and benefits of these drugs among health professionals and patients. In order to achieve these goals, it is important to assess the current ideas and concerns of patients regarding GCs.Objectives:To evaluate the current patient perspective on the efficacy and risks of GCs in RA patients who are or have been treated with GCs.Methods:Patients with RA completed an online survey (with 5 closed questions regarding efficacy and safety) presented in their native language. RA patients were recruited through a variety of patient organizations representing three continents. Patients were invited to participate through national patient organizations. In the USA, patients were also invited to participate through MediGuard.org. Participants were asked for their level of agreement on a 5-point Likert scale.Results:1344 RA patients with exposure to GCs, from Brazil, USA, UK, Portugal, Netherlands, Germany and 24 other countries** participated: 89% female, mean age (SD) 52 (14) years and mean disease duration 13 (11) years. The majority of participants (84%) had ≥10 years of education. The duration of GCs exposure was 1.6 (4.2) years. The majority of participants had read articles or pamphlets on the benefits or harms of GC therapy.Regarding GCs efficacy (table 1), high levels of endorsement were found: about 2/3 of patients considered that GCs as very useful in their case, more than half considered that GCs were effective even at low doses, and agreed that GC improved RA symptoms within days.Regarding safety (table 1), 1/3 of the participants reported having suffered some form of serious adverse events (AEs) due to GCs, and 9% perceived this as “life-threatening. Adverse events had a serious impact on quality of life, according to about 1/3 of the respondents.Conclusion:Patients with RA exposed to GC report a strong conviction that GCs are very useful and effective for the treatment of their RA, even at low doses. This is accompanied by an important prevalence of serious AEs. Understanding the patient perspective can improve shared decision-making between patient and rheumatologist.Funding statement:This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634886.Disclosure of Interests:Tânia Santiago: None declared, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Pedro Carvalho: None declared, Maarten Boers: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis

scholarly journals Pilot study in patients with congenital low-flow vascular malformation treated with low dose sirolimus

2020 ◽  
Author(s):  
Veroniek Harbers ◽  
Gerard Rongen ◽  
van der Carine Vleuten ◽  
Bas Verhoeven ◽  
de Peter Laat ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Vascular Malformation ◽  
Low Dose ◽  
Liver Toxicity ◽  
Vascular Malformations ◽  
Low Flow ◽  
Bone Marrow Toxicity ◽  
Serious Adverse Events ◽  
Grade Iii

Abstract Background Patients with congenital low-flow vascular malformations (capillary (CM), lymphatic (LM), venous (VM) or combined) may have an impaired quality of life (QoL), due to their symptoms, which include pain, swelling, bleeding, thrombosis, and functional impairment. Unfortunately, current treatment methods are challenging and not always successful. Previous studies have shown that the mTOR-inhibitor sirolimus is an effective treatment for these patients. Target levels of 10–15 ng/ml were well tolerated; however, grade three adverse events were observed (ranged 20–40%). Methods A pilot study was performed using a Challenge–Dechallenge–Rechallenge (CDR) design to determine the pharmacodynamics of low target levels of sirolimus (target levels 4–10 ng/ml) in respect of efficacy and adverse events in patients with disabling low-flow vascular malformations without treatment alternatives. The patients received sirolimus over a three-to-six-month period (Challenge), followed by the withdrawal of sirolimus (Dechallenge). If the complaints returned, sirolimus was reintroduced during a twelve month period (Rechallenge). Efficacy was determined on pain (end point of the pilot study) and other symptoms related to the vascular malformation; and adverse events were determined in all phases of the study. Results An improvement in symptoms was seen in 92% (n = 11/12) of patients during the Challenge phase. In the Rechallenge phase, a positive response rate of 78% was found (n = 7/9). These response rates are comparable to those found in the literature despite low target levels of sirolimus. However, less serious adverse events were observed with low dose sirolimus, especially bone marrow toxicity and grade III liver toxicity. Conclusions This pilot using low dose sirolimus showed high efficacy in patients with therapy resistant and disabling low-flow malformation, with a lower incidence of serious adverse events (especially bone marrow toxicity and grade III liver toxicity). This is extremely relevant to patients with low-flow vascular malformation, as current clinical protocols tend to advise lifelong treatment. Trial registration The pilot study was part of a phase III study. Trial registration: EudraCT number: 2016-002157-38 and ClinicalTrials.gov Identifier: NCT03987152, registered 06/14/2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03987152?term=sirolimus&cond=Vascular+Malformations&cntry=NL&draw=2&rank=1

scholarly journals Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

2020 ◽  
Vol 38 (10) ◽  
pp. 1006-1018 ◽  
Author(s):  
Kim-Hien T. Dao ◽  
Jason Gotlib ◽  
Michael M.N. Deininger ◽  
Stephen T. Oh ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Symptom Assessment ◽  
Complete Response ◽  
Serious Adverse Events ◽  
Chronic Neutrophilic Leukemia ◽  
Atypical Chronic Myeloid Leukemia ◽  
Grade 3

PURPOSE Colony-stimulating factor-3 receptor ( CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status. METHODS We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade ≥ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival. RESULTS ORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade ≥ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed. CONCLUSION Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond.

A Nationwide Investigation of a Possible Protamine Drug-Product Defect

1992 ◽  
Vol 26 (5) ◽  
pp. 643-644 ◽  
Author(s):  
Carlos R. Herrera ◽  
Thaddeus H. Grasela ◽  
Cynthia A. Walawander
Keyword(s):  
Coronary Artery ◽  
Adverse Events ◽  
Coronary Artery Bypass ◽  
Response Rate ◽  
Artery Bypass ◽  
Drug Surveillance ◽  
Surveillance Network ◽  
Serious Adverse Events ◽  
Telephone Interviews

OBJECTIVE: To follow-up a report submitted to FDA Spontaneous Reporting System, we investigated the hypothesis that there was not a striking increase in unexpected deaths within four hours after elective coronary artery bypass surgery associated with protamine sulfate use. DESIGN: Surveys were mailed to clinical pharmacists at 521 hospitals participating in the Drug Surveillance Network. Questionnaires were to be completed with the assistance of cardiac surgeons and anesthesiologists. Hospitals responding with a suspected problem with protamine were contacted via telephone. RESULTS: Surveys were received from clinical pharmacists at 380 hospitals (73 percent response rate) and 29 hospitals reported the occurrence of potential problems associated with protamine during coronary artery bypass graft surgery. Telephone interviews of the positive responders yielded six cases of possible myocardial decomposition potentially associated with protamine. There was no association with a specific distributor, however, and none of the hospitals reported a dramatic increase in serious adverse events around the time of index cases. CONCLUSIONS: There was no evidence of a widespread public health problem with protamine and a product recall was not necessary. The high response rate and the ability to follow-up with telephone interviews suggests that the Drug Surveillance Network is an effective mechanism for investigating possible outbreaks of serious adverse events in the hospital setting.

Assessing the effect of immunosuppressive agents for immune-related adverse event management on tumor response.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3066-3066
Author(s):  
Pankti Reid ◽  
Daniel Olson ◽  
Thomas Gajewski
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Tumor Response ◽  
Immunosuppressive Agents ◽  
Objective Response ◽  
Treatment Algorithm ◽  
Tumor Control ◽  
High Dose ◽  
High Grade ◽  
Steroid Dependent

3066 Background: High grade immune-related adverse events (irAEs) to cancer immune checkpoint inhibitors (ICI) require considerable immunosuppression (IS) with high-dose steroids and steroid-sparing IS (SSIS) for steroid-dependent cases. T lymphocyte-specific IS has generally been avoided or used with significant caution due to the fear that these agents may negatively impact ICI efficacy. We sought to determine whether T cell-specific IS agents, such as calcineurin inhibitors (CNIs), have an adverse effect on tumor control when compared to other immunomodulatory drugs (IMDs). Methods: We retrospectively analyzed clinical annotations of adult patients treated with ICIs for malignancy from 1/1/2000-12/31/2019, highlighting patients who were managed with SSIS, specifically those most commonly used for autoimmune disease therapy. Topical IS use was excluded. Patients were categorized as tumor responders or non-responders, and irAEs were graded according to National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Progression-free survival (PFS) was assessed via Kaplan-Meier curve. Results: 1331 unique individuals were prescribed ≥1 ICIs, with 526 prescribed systemic steroids (39.5%) and 90 (6.8%) patients prescribed SSIS agents, 25 patients with >1 SSIS: mycophenolate (39), methotrexate (26), leflunomide (5), azathioprine (3), rituximab (24), tocilizumab (3), infliximab (8), etanercept (1), adalimumab (1), golimumab (1) and CNIs (18): cyclosporine, tacrolimus. IMDs hydroxychloroquine (6) and sulfasalazine (5) were also prescribed. The objective response rate was 50.0% in the CNI group compared to 45.5% in the IMD cohort and 45.4% in the irAE group (CTCAE grade matched) with steroids alone without any SSIS. Median PFS were compared between CNI cohort (5.4 months, range 1.3-34 months) to IMD (1.1 months, range 0.4-6.4, p=0.02) and steroid alone (2.4 months, range 0.69-17.7, p=0.48). Multiple regression analysis identified irAE presence as an independent correlates to tumor response (p=0.02). Conclusions: T cell-specific IS should not be excluded from irAE treatment algorithm as we observed that PFS was comparable to immunomodulators and similar efficacy was observed compared to steroids alone. Rapid identification and management of irAEs can help mitigate morbidity but there are virtually no reliable clinical trials to guide irAE management with SSIS. These findings support the need for larger, prospective evaluation of immunosuppression use for high grade irAE therapy.

scholarly journals FINAL Results of an Phase, Multicenter, Randomied, Controlled OPEN LEVEL Trial: Decitabine Therapy in Patients with Myelodysplastic Syndromes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3865-3865
Author(s):  
Zonghong Shao ◽  
Hui Liu ◽  
Hao Jiang ◽  
Hongyan Tong ◽  
Ruixiang Xiang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Adverse Events ◽  
Myelodysplastic Syndromes ◽  
Overall Response Rate ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Study Drug ◽  
Overall Response ◽  
To Receive

Abstract Background: DNA hypomethylating agent, decitabine, has become the current standard therapy for patients with higher-risk myelodysplastic syndromes (MDS). Decitabine was launched in China in August 2009 without clinical trials. According to some retrospective studies, the efficacy and safety are similar to those reported in other countries, but there is still a lack of large-scale prospective clinical trials. So we start a prospective clinical trial in China to compare the effect and safety of decitabine in MDS, which was registered at clinicaltrials.gov (NCT02013102). Design: Adults with intermediate or high risk MDS by the International Prognostic Scoring System (IPSS≥0.5) were randomized to receive either decitabine 20 mg/m2 IV daily for 5 days (arm Ⅰ) or decitabine 12 mg/m2 IV daily for 8 days (arm Ⅱ) every four weeks. Patients continued to receive study drug for 4 cycles until death, disease progression, intercurrent illness preventing further administration of treatment, unacceptable adverse event or decision by the patient to withdraw from the study. And supportive care were permitted. The primary end point was overall response rate (ORR, CR+mCR+PR) by International Working Group (IWG 2006) criteria, secondary end points included CR, mCR, PR, HI, safety, et al. Results: We enrolled a total of 198 patients between 8/2013 and 12/2017, among which 7 patients didn't take decitabine, and 191 were included in the analysis. 94 in arm Ⅰ recieved decitabine and 97 in arm Ⅱ. 32.8% of patients withdrew from the study for a variety of reasons, including progression and death (5.1%), personal decision (13.6%), adverse events (6.6%), and other causes (7.6%). The median age of patients in arm Ⅰ was 54.88 years old and 54.82 years old in arm II. The median follow-up was 106 days for patients in both arms. The patients received a mean 2.5 cycles of decitabine therapy for arm Ⅰ and 2.0 cycles for arm Ⅱ. The overall response rate was 39.3% in total, and 41.5% and 38.1% (p=0.6598) for patients in arm Ⅰ and arm Ⅱ, respectively. And CR was 18.1% and 14.4% (p= 0.5584) , PR was 6.4% and 3.1% (p=0.3257) , mCR was 17.0% and 20.6% (p=0.5814) , HI was 3.2% and 1.0% (p=0.3633) , for patients in armⅠand armⅡ, respectively (Table 1). Among all patients, 38.7% were intermediate-1 risk, 40.3% were intermediate-2 risk, 20.4% were high risk. Analysis of response by MDS patient subtypes is shown in Table 2. Those who were higher risk experienced higher ORR and CR, while the difference is not significant between two arms (p>0.05). As expected, cytopenias were the most frequent complications (76.4%). Grade 3-4 neutropenia, thrombocytopenia and anemia considered to be at least possibly related to the study drug occurred at rates of 23.0%, 34.6%, and 34.6% of patients, respectively. Nonhematologic adverse events were also common including abnormal metabolism and nutrition (23.40% vs 18.56%), abnormal gastrointestinal function (29.79% vs 41.24%), cardiac disorders (11.70% vs 14.43%), infection and infectious diseases (32.98% vs 36.08%), abnormal skin and subcutaneous tissue and so on, which were no significant differences between two ams. During the study there were 17 SAE, only 7 cases were possibly related to drug therapy, such as pulmonary infection, Sepsis, myelosuppression, intracranial hemorrhage, hepatic failure, and arrhythmia. Conclusions: The use of 5-day and 8-day schedule decitabine is safe and effective in patients with intermediate and high risk MDS, among which there was no significant differences. Disclosures No relevant conflicts of interest to declare.

Patients’ and rheumatologists’ perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis—an international survey within the GLORIA study

Rheumatology ◽  
2021 ◽  
Author(s):  
T Santiago ◽  
M Voshaar ◽  
M de Wit ◽  
P D Carvalho ◽  
F Buttgereit ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Professionals ◽  
Low Dose ◽  
Unmet Need ◽  
Signs And Symptoms ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
The Real ◽  
Patient Organizations ◽  
Published Evidence

Abstract Objective To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA. Methods Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys. Results A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map. Conclusions RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.

Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7578-7578 ◽  
Author(s):  
A. Santoro ◽  
J. Voglova ◽  
N. Gabrail ◽  
T. Ciuleanu ◽  
M. Liberati ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
International Workshop ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Time To Progression ◽  
Open Label ◽  
Ecog Performance Status ◽  
Serious Adverse Events

7578 Background: BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines, demonstrates single agent activity in patients with NHL, and does not exhibit cardiotoxic effects in animal models. This phase III open-label study was designed to compare the efficacy and tolerability of combination rituximab and BBR 2778, with that of single agent rituximab, in patients (pts) with relapsed or refractory indolent NHL. Methods: Pts were randomly assigned to receive both rituximab and BBR 2778 (experimental arm), or rituximab alone (control arm). In the experimental arm, pts received 375 mg/m2 rituximab IV on days 1 and 8 of cycles 1 and 2 only, and 90 mg/m2 BBR 2778 IV on days 2 and 8 of cycle 1, and on days 1 and 8 of all subsequent cycles. Pts could receive six 21-day cycles of BBR 2778. In the control arm, pts received 375 mg/m2 rituximab IV on days 1, 8 and 15 of cycle 1 and day 1 of cycle 2 only. Disease response was assessed every other cycle according to International Workshop to Standardize Response Criteria for NHL. Toxicities were assessed throughout the study using NCI-CTC criteria. Study was closed early due to poor enrollment. Results: 38 pts (20 experimental, 18 control) were enrolled. Mean age was 66 and 59 years in the experimental and control arm, respectively. Most patients were males and most had ECOG performance status 0 or 1. Efficacy is summarized in the table. Response rate (75 vs 33%) and time to progression (13.2 vs 8.1 months) were better in the BBR 2778 arm. Only pts in the experimental arm had study drug related serious adverse events (2 febrile neutropenia, 1 pneumonia, 1 neutropenia) and adverse events resulting in withdrawal (6 vs 0). Conclusions: Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate. BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL. [Table: see text] [Table: see text]

A phase II trial of low-dose nab-paclitaxel for patients with previously treated or recurrent advanced gastric cancer (OGSG1302).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 350-350
Author(s):  
Masashi Hirota ◽  
Shigeyuki Tamura ◽  
Hirokazu Taniguchi ◽  
Atsushi Takeno ◽  
Hiroshi Imamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Phase Ii ◽  
Low Dose ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Dose Intensity ◽  
Relative Dose Intensity ◽  
Grade 3

350 Background: Paclitaxel is a key drug in second-line chemotherapy for advanced or recurrent gastric cancer (AGC) and nanoparticle albumin-bound paclitaxel (nab-PTX) is also widely used in Japan. A previous phase II trial in Japan showed the effectiveness of nab-PTX (260 mg/m2) administered every 3 weeks (q3w) in patients with AGC with a response rate (RR) of 27.8%; however, toxicity was major concern with grade ≥3 neutropenia (49.1%) and peripheral neuropathy (23.6%). To solve this problem, we investigated the efficacy and safety of low-dose q3w nab-PTX regimen in AGC. Methods: Eligibility requirements included: aged ≥20 years, HER2-negative, histologically confirmed, unresectable or recurrent gastric adenocarcinoma, one or more prior chemotherapy containing fluoropyrimidine regimens, presence of measurable lesion(s) according to RECIST ver. 1.1, ECOG PS of 0–2, and adequate organ function. Nab-PTX was administered at a dose of 220 mg/m2 every 3 weeks. The primary endpoint was the RR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity and proportion of patients who received subsequent chemotherapy. Results: Thirty-three patients were enrolled from 10 institutions in Japan. Of the 32 patients treated with protocol therapy, RR (CR, PR) was 3.1% (95% CI, 0–16.2%), which was not reached the protocol-specified threshold (p = 0.966). DCR (CR, PR, SD) was 37.5% (95% CI, 21.1–56.3%), median OS and PFS were 6.3 months (95% CI, 4.4–14.2) and 2.2 months (95% CI, 1.8-3.1). Relative dose intensity was 97.8% (215 mg/m2). 62.5% of patients received subsequent chemotherapy. Most common grade ≥3 adverse events were neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). Conclusions: Low-dose regimen of q3w nab-PTX was slightly less toxic, although it did not demonstrate the same effect as the original regimen in response rate. Therefore, it is not recommended for AGC in second or later line setting. Clinical trial information: UMIN 000012701.

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