We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small ...lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio HR 95% CI, 0.206 0.159-0.265; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.
Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The WHO classification offers prognostic information and helps with the treatment decisions. However, morphological ...changes are subject to potential inter-observer variance. The aim of our study was to explore the reliability of the 2008 WHO classification of MDS, reviewing 100 samples previously diagnosed with MDS using the 2001 WHO criteria. Specimens were collected from 10 hospitals and were evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the 2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered suitable (27 %). Although there were a high number of observers taking part, the rate of discordance was quite similar among the five pairs. The inter-observer concordance was very good regarding refractory anemia with excess blasts type 1 (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74 %). However, the categories with unilineage dysplasia were not reproducible in most of the cases. The rate of concordance with refractory cytopenia with unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring sideroblasts (two of eight). Our results show that the 2008 WHO classification gives a more accurate stratification of MDS but also illustrates the difficulty in diagnosing MDS with unilineage dysplasia.
Summary Background Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or ...refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. Methods The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m2 intravenously on days 2–3 in cycle 1, and days 1–2 in cycles 2–6; rituximab: 375 mg/m2 on day 1 of cycle 1, and 500 mg/m2 on day 1 of cycles 2–6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression-free survival. Crossover to ibrutinib was permitted for patients in the placebo group with IRC-confirmed disease progression. Analysis was by intention-to-treat and is continuing for further long-term follow-up. The trial is registered with ClinicalTrials.gov , number NCT01611090. Findings Between Sept 19, 2012, and Jan 21, 2014, 578 eligible patients were randomly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab (289 in each group). The primary endpoint was met at the preplanned interim analysis (March 10, 2015). At a median follow-up of 17 months (IQR 13·7–20·7), progression-free survival was significantly improved in the ibrutinib group compared with the placebo group (not reached in the ibrutinib group (95% CI not evaluable) vs 13·3 months (11·3–13·9) in the placebo group (hazard ratio HR 0·203, 95% CI 0·150–0·276; p<0·0001). IRC-assessed progression-free survival at 18 months was 79% (95% CI 73–83) in the ibrutinib group and 24% (18–31) in the placebo group (HR 0·203, 95% CI 0·150–0·276; p<0·0001). The most frequent all-grade adverse events were neutropenia and nausea. 222 (77%) of 287 patients in the ibrutinib group and 212 (74%) of 287 patients in the placebo group reported grade 3–4 events; the most common grade 3–4 adverse events in both groups were neutropenia (154 54% in the ibrutinib group vs 145 51% in the placebo group) and thrombocytopenia (43 15% in each group). A safety profile similar to that previously reported with ibrutinib and bendamustine plus rituximab individually was noted. Interpretation In patients eligible for bendamustine plus rituximab, the addition of ibrutinib to this regimen results in significant improvements in outcome with no new safety signals identified from the combination and a manageable safety profile. Funding Janssen Research & Development.
Synovial sarcomas are uncommon soft tissue malignancies that usually affect the extremities in the vicinity of large joints. The recognition of this tumor in an unexpected site, such as the pleura, ...is often difficult and the monophasic variant of synovial sarcoma is often mistaken for some other spindle cell tumor. In this report, we describe a very rare case of primary monophasic synovial sarcoma of the pleura treated with radical surgery.
Objectives
Empyema is a severe condition, which needs adequate and expeditious treatment. Different modalities can be considered, from single drainage placement to open window thoracostomy. ...Videothoracoscopic decortication unites the goals of good lung re-expansion with minimally invasive surgery, but ocassionally in chronic pleural empyema, this procedure is not easy and requires conversion to open surgery. The aim of this paper is to evaluate the feasibility of this approach in such cases and to perform a comparative study with open decortication.
Methods
We have performed a retrospective comparative analysis of a prospective database. From 2000 to 2011, 186 patients suffering from empyema were admitted in our Department. Sixty (32.8%) of them needed decortication, 27 by videothoracoscopy (Group A) and 34 by thoracotomy (Group B). Variables: operative time, complications, days of drainage, postoperative length of stay (LOS) and mortality. Statistical analysis: homogeneity between videothoracoscopic and thoracotomy groups was evaluated. Student's t-test was used for continuous variable, unpaired t-test was used for operative time, LOS and days of drainage. Chi2-test was used for categorical data. Significance level P = 0.05 (SSPS 17 Software).
Results
Pleural decortication was performed in stage III chronic empyema with excellent results and only 3 patients needed conversion (11.1%). Comparison: Operative time: Group A 135 min (65-175), Group B 160 min (90-240). No significative. Complications: Group A 8.2%, Group B 14.7%, P < 0.05. Days of drainage: Group A 5.9 ± 2 days, Group B 9.3% ± 2 days, P < 0.05. LOS: Group A 7.8 days, Group B 11.4 days, P < 0.05. Mortality: Group A 1 (1.6%), Group B 3 (4.9%) No significative.
Conclusions
Videothoracoscopic decortication is a feasible procedure in stage III empyema with equally effective resolution as thoracotomy. Furthermore in our series it has better results in operative time, postoperative morbidity and length of stay. Multicentric-randomized trial should be performed to suggest this approach as gold standard of pleural empyema.
Disclosure
All authors have declared no conflicts of interest.
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