Multicentre, randomised, open-label, non-inferiority trial comparing the effectiveness and safety of ductal lavage versus oral corticosteroids for idiopathic granulomatous mastitis: a study protocol

IntroductionThe ideal treatment for idiopathic granulomatous mastitis (IGM) remains unclear. In a prospective, single-centre, pilot study, we reported that ductal lavage treatment for non-lactational mastitis patients had a 1-year clinical complete response (cCR) rate of >90%, without any significant adverse events. Thus, in this multicentre, randomised, open-label, non-inferiority trial, we will aim to compare the effectiveness and safety of ductal lavage vs oral corticosteroids as the first-line treatment for patients with IGM.Methods and analysisThe trial will be conducted at the Breast Tumor Center of Sun Yat-sen Memorial Hospital in China and at least at one participating regional centre. We plan to recruit 140 eligible IGM patients who will be randomised into the ductal lavage group or oral corticosteroid group with a 1:1 ratio. The patients in the oral corticosteroid group will receive meprednisone or prednisone for 6 months. The patients in the ductal lavage group will receive ductal lavage and breast massage, as previously reported. All the participants will be followed up at the clinic for 1 year post randomisation. The primary endpoint of this trial will be the 1-year cCR rate, and the secondary endpoints will include the time to cCR, treatment failure rate, relapse rate and protocol compliance rate. The trial was designed to determine whether ductal lavage is non-inferior to oral corticosteroids (1-year cCR rate assumed to be 90%), with a non-inferiority margin of 15%.Ethics and disseminationThe ethics committee of Sun Yat-sen Memorial Hospital at Sun Yat-sen University approved the study (2018-Lun-Shen-Yan-No. 30). The results of the trial will be communicated to the participating primary care practices, published in international journals and presented at international clinical and scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT03724903); Pre-results.

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Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis

Journal of Clinical Medicine ◽

10.3390/jcm10102077 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2077

Author(s):

Yi-Min Huang ◽

Chiao Lo ◽

Chiao-Feng Cheng ◽

Cheng-Hsun Lu ◽

Song-Chou Hsieh ◽

...

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Serum Biomarkers ◽

Healthy Controls ◽

Granulomatous Mastitis ◽

C Reactive Protein ◽

Idiopathic Granulomatous Mastitis ◽

Reactive Protein

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

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Out Come of Wide Local Excision with and without Corticosteroid Therapy in Management of Idiopathic Granulomatous Mastitis

Tumori Journal ◽

10.1177/03008916211012342 ◽

2021 ◽

Vol 107 (1_suppl) ◽

pp. 13-13

Author(s):

R Amira Maher ◽

Ahmed Gamal Eldin Osman ◽

K Fahmy ◽

Shinamwi M ◽

Osama Al Atarash

Keyword(s):

Recurrence Rate ◽

Corticosteroid Therapy ◽

Surgical Excision ◽

Cosmetic Outcome ◽

Systemic Steroid ◽

Granulomatous Mastitis ◽

Idiopathic Granulomatous Mastitis ◽

Palpable Mass ◽

Group A ◽

Group B

Introduction: Idiopathic granulomatous mastitis is a rare benign breast disease. Initial reports from hospitals in Egypt from Departments of Pathology at Cancer Institutes of Cairo, Tanta and Mansoura Universities; indicate that the disease is not as rare as that in the developed countries. It often mimics breast carcinoma both clinically and radiologically. Histological examination is the gold standard for diagnosis. Management of Idiopathic granulomatous mastitis is still debatable. In our study, we aimed to evaluate the addition of corticosteroid therapy to surgical excision in management of idiopathic granulomatous mastitis. Patients and Methods: This is a comparative study was conducted at Ain-Shams University Hospital’s breast clinic on patients with idiopathic granulomatous mastitis from to August 2015 till September 2018. Thirty patients were divided into 2 groups. Group (A) includes patients who underwent surgical management only. Group (B) includes patients who received corticosteroid therapy according to the severity of the cases then surgical Excision was done for the residual lesion. Follow up of all cases up to 1-2 years was done to document the recurrence rate and compare the cosmetic outcome of both groups. Informed consent was obtained from all patients included in the study. Results: The mean age of the affected women was 38.80 and 33.13 in group (A) and group (B), respectively and it wasn’t statistically different (p value = 0.099). The most common presenting symptom was a palpable mass in the breast (66.7% and 93.3%) in group (A) and group (B) respectively. Recurrence rate was higher in group (A) (40%) with no recurrence documented in group (B) however 2 cases were omitted from the study due to steroid noncompliance and complications. Cosmetic outcome was excellent in 76.9% of group (B) and good in 53.3% of group (A). Conclusion: Systemic steroid therapy with surgical resection is the recommended as first-line treatment strategy for IGM as it shows less recurrence rate and surgical scarring. Increased awareness of IGM will increase their understanding and improve their management.

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Idiopathic granulomatous mastitis: challenges of treatment in iranian women

BMC Surgery ◽

10.1186/s12893-021-01210-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Leyla Shojaee ◽

Nasrin Rahmani ◽

Siavash Moradi ◽

Asieh Motamedi ◽

Gholamali Godazandeh

Keyword(s):

Recurrence Rate ◽

Low Dose ◽

Unknown Origin ◽

Surgical Excision ◽

Chronic Inflammatory Disease ◽

High Dose ◽

Granulomatous Mastitis ◽

Idiopathic Granulomatous Mastitis ◽

Results Of Treatment ◽

Information Treatment

Abstract Background and objective As a chronic inflammatory disease of an unknown origin, the treatment of granulomatous mastitis has always been controversial. According to some researchers, surgical treatment and certain medications, especially steroids, are more effective in treating the disease. This study aimed at evaluating the results of treatment in a group of patients with granulomatous mastitis. Materials and methods This longitudinal cohort study evaluated the treatment outcomes of 87 patients with pathology-confirmed granulomatous mastitis referred to the surgical clinic of Central Hospital in Sari, Iran. Demographic, clinical, and pathological information, treatment methods and results, and the recurrence rate were analyzed. Findings A total of 87 female patients with granulomatous mastitis aged 22–52 years with a mean age of 34 years were evaluated. All patients had palpable masses; the breast masses were painful in 48.3% of patients, and 55.2% of patients suffered from erythema and inflammation, and8% had fistulas and ulcers at the inflammation site. The patients were followed-up for an average duration of 26 months (8–48 months) after treatment and recovery. The overall recurrence rate was 24.1%, and the recurrence rate was 29.4% in patients underwent surgery, 34.8% in patients received high-dose prednisolone, and 17% in those received low-dose prednisolone together with drainage (p < 0.001). Conclusions According to the results, the low-dose prednisolone plus drainage was more effective with a lower recurrence rate than only surgical excision or high-dose prednisolone. In fact, the use of minimally invasive methods such as drainage plus low-dose steroids is a more effective method with fewer side effects than the other two methods.

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804 A phase II study of the anti-programmed cell death-1 (PD-1) antibody penpulimab in patients with metastatic nasopharyngeal carcinoma (NPC) who had progressed after two or more lines of chemotherapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0804 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A853-A853

Author(s):

Xiaozhong Chen ◽

Wei Wang ◽

Qingfeng Zou ◽

Jingao Li ◽

Chaosu Hu ◽

...

Keyword(s):

Disease Progression ◽

Receptor Occupancy ◽

Complete Response ◽

Hepatic Function ◽

Open Label ◽

Barr Virus ◽

Duration Of Response ◽

Epstein Barr ◽

Grade 3 ◽

Anti Tumor Activity

BackgroundNPC is rare but has a distinct geographic distribution, with a predominance in Southeast Asia. Favorable results with PD-1 inhibitors in NPC provide a strong rationale to investigate penpulimab in this disease. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely,where ADCC/ADCP effects can induce T-cell apoptosis and clearance and then compromise anti-tumor activity. Penpulimab demonstrated a slower PD-1 antigen binding off-rate than marketed PD-1 antibodies, which result in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and may contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab.MethodsAK105-202 (NCT03866967) is a multicenter, single-arm, open-label study of penpulimab in metastatic NPC patients (pts) with disease progression after ≥2 prior lines of therapy including platinum-containing chemotherapy. All patients received penpulimab 200 mg q2w until progression or unacceptable toxicity. The primary endpoint was ORR based on RECIST v1.1 as assessed by an independent review committee (IRC). Key secondary endpoints included DCR, PFS, duration of response (DoR). Archived tissues were retrieved for the analysis of PD-L1 (Shuwen SAB-028). PD-L1 expression of tumor proportion score (TPS)≥50% was regarded as positive. Plasma Epstein-Barr virus DNA were obtained for biomarker correlative analysis.ResultsAs of 18 September 2020, the median follow-up was 7.9 months (range 0.9 to 16.9). The anti-tumor activity of penpulimab in the 111 pts with disease progression after ≥2 prior lines of therapy evaluable for efficacy (defined as pts who had an opportunity to be followed for at least 16 weeks and had measurable disease at baseline per RECIST v1.1) is shown in the table 1.Treatment-related adverse events (TRAEs, including unlikely related) occurred in 79.2% of pts (≥G3 in 14.6% [19/130], treatment discontinuation in 3.1% [4/130]). Treatment-related SAEs occurred in 10.0% [13/130]. Most frequent TRAEs (≥10%) were fever (24.5%), hypothyroidism (24.6%), anemia (23.1%), ALT increased (17.0%) and WBC decreased (10.8%). Grade ≥3 TRAEs (≥2%) were hepatic function abnormal (2.3%) and anemia (2.3%).Abstract 804 Table 1a. Including 1 complete response and 29 partial response. At data cutoff, 90% of responders remained ongoing.b.43 pts were PD-L1 positive (TPS≥50%) and 66 pts were PD-L1 negative (TPS<50%).c. Including 1 ongoing response awaiting confirmation classified under SD.ConclusionsPenpulimab demonstrated encouraging anti-tumor activity and favorable safety profile in pts with disease progression after ≥2 prior lines of therapy. A higher proportion of objective responses was observed in NPC pts with PD-L1–positive tumors receiving penpulimab than those with PD-L1–negative tumors.

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The Role of Conservative Treatment in Idiopathic Granulomatous Mastitis

The Breast Journal ◽

10.1111/j.1075-122x.2005.00127.x ◽

2005 ◽

Vol 11 (6) ◽

pp. 454-456 ◽

Cited By ~ 110

Author(s):

Eric C. H. Lai ◽

Wing Cheong Chan ◽

Tony K. F. Ma ◽

Alice P. Y. Tang ◽

Cycles S. P. Poon ◽

...

Keyword(s):

Conservative Treatment ◽

Granulomatous Mastitis ◽

Idiopathic Granulomatous Mastitis

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Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7545 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7545-7545

Author(s):

Miguel Angel A. Canales Albendea ◽

Thomas A. Buchholz ◽

Koji Izutsu ◽

Takayuki Ishikawa ◽

Laura Maria Fogliatto ◽

...

Keyword(s):

Follicular Lymphoma ◽

Stage Iv ◽

Progression Free Survival ◽

Response Assessment ◽

Complete Response ◽

Primary Analysis ◽

Open Label ◽

Secondary Endpoints ◽

To Receive ◽

Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

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Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8004 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8004-8004

Author(s):

Philippe Moreau ◽

Pieter Sonneveld ◽

Keyword(s):

Interim Analysis ◽

Residual Disease ◽

Progression Free Survival ◽

Complete Response ◽

Autologous Stem Cell Transplant ◽

Second Primary ◽

Cell Transplant ◽

Open Label ◽

Depth Of Response

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.

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