Agnieszka Giza

Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial.

BACKGROUND Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigators choice of single-agent therapy in relapsed or refractory mantle cell lymphoma. METHODS The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0-2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1-21 every 28 days) until progressive disease or intolerability, or single-agent investigators choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigators choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigators choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667. FINDINGS Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigators choice monotherapy). Patients had a median age of 68·5 years and received a median of two previous regimens. With a median follow-up of 15·9 months (IQR 7·6-31·7), lenalidomide significantly improved progression-free survival compared with investigators choice (median 8·7 months [95% CI 5·5-12·1] vs 5·2 months [95% CI 3·7-6·9]) with a hazard ratio of 0·61 (95% CI 0·44-0·84; p=0·004). In the 167 patients in the lenalidomide group and 83 patients in the investigators choice group who received at least one dose of treatment the most common grade 3-4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]). INTERPRETATION Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigators choice options. FUNDING Celgene Corporation.

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m2 per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.

Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group

Abstract We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1–190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63–0.85) and 0.90 (95%CI: 0.82–0.98) for ES; 0.51 (95%CI: 0.44–0.57), and 0.81 (95%CI: 0.75–0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma

Abstract Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520–1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472–0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

Primary mediastinal B-cell lymphoma – metabolic and anatomical features in 18FDG-PET/CT and response to therapy

Aim of the study Determining the role of PET/CT imaging in the evaluation of treatment efficacy in primary mediastinal B-cell lymphoma (PMBCL). Material and methods Retrospective analysis of seven PMBCL patients, treated at the University Hospital in Krakow, with interim PET/CT after the third course of chemo-immunotherapy.The analysis was based on the calculation of exact tumour volume and metabolic activity, compared with initial values (directly after diagnosis). Results Patients (five females, two males, average age 26.2 years, range 18–40 years), in clinical stage IIBX at diagnosis, were treated with eight cycles of R-CHOP-14 regimen, with radiotherapy consolidation (7/7) and central nervous system prophylaxis (6/7). The observed decrease in tumour volume between the initial staging and the interim PET ranged 72–89%. The mean ΔSUVmax reduction between initial (when available) and interim PET was 87% (range 84–89%). In 3/7 cases in the interim PET/CT, the uptake of the tumour was higher than the liver (Deauville Criteria score 4–5), and in 4/7 it was lower than the liver but higher than mediastinal blood pool structures (score 3 according to Deauville Criteria). After a median follow-up of 58 months – OS and EFS is 100%. Conclusions The excellent clinical outcome in the study group corresponds with very good metabolic and volumetric response in the interim PET. The ΔSUVmax seems to be easier in implementation and has a more significant impact than other measurements.

Scalp skin primary cutaneous follicle center lymphoma – Case report

Primary cutaneous follicle center lymphoma is defined as the neoplastic proliferation of follicle center cells affecting the skin. It is classified as Indolent Cutaneous B-cell Lymphoma and is the most common primary B-cell lymphoma of the skin representing almost 11% of cutaneous lymphomas. There are three different growth patterns of the PCFCL: follicular, a follicular and diffuse, or a diffuse type. Neither of them is characterized by a worse or better prognosis [1,2].