Introduction Treatment with chimeric antigen receptor modified T cells targeting CD30 (CD30.CAR-Ts) without lymphodepletion was found to be safe with preliminary efficacy in patients (pts) with relapsed/refractory (r/r) CD30+ lymphomas (Ramos et al., JCI 2017). We report the results of a phase 1b/2 trial of CD30.CAR-Ts infused after lymphodepletion in pts with r/r CD30+ Hodgkin (HL) and Non-Hodgkin lymphoma (NHL). Objectives The primary objective of the phase Ib portion of the study was to determine the phase 2 dose of CD30.CAR-Ts using a standard 3+3 design. Methods Pts ≥ 18 years with r/r CD30+ HL or NHL having failed ≥2 prior therapies were eligible. Two dose levels were tested: 1 × 108 CAR-Ts/m2 (DL1) and 2 × 108 CAR-Ts/m2 (DL2). The first 8 pts (including the 3 pts on DL1) received bendamustine (benda) 90 mg/m2 × 2 days and the remaining 16 pts received benda 70 mg/m2 and fludarabine (flu) 30 mg/m2 × 3 days. Results At the time of data cut off (10/1/2018), 24 pts had been treated and undergone response assessment. The median age was 35.5 years (range: 23-70). 22 pts had HL, 1 had enteropathy associated T cell lymphoma and 1 had Sezary syndrome. Pts had undergone a median of 7.5 prior lines of therapy (range: 3-17). 23 pts had received prior brentuximab vedotin. 15 pts had prior autologous stem cell transplant (SCT) and 7 had prior allogeneic SCT. As there were no dose limiting toxicities, DL2 was administered as the phase 2 dose. 3 pts developed grade 1 cytokine release syndrome (CRS) and 1 pt had grade 2 CRS which responded to tocilizumab. 19 out of 24 pts had evidence of disease prior to lymphodepletion and were included in efficacy analysis. 10 pts had a CR at the 6 week assessment (53%, all in benda/flu cohort), 2 had partial response (11%), 2 had stable disease (11%), and 5 had progressive disease (26%, including all 3 pts treated at DL1). At median follow up of 180 days, the median PFS was 164 days. The median PFS for the 14 evaluable pts who received benda/flu at DL2 was 389 days. Using peripheral blood PCR, CD30.CAR-Ts peaked at wk 2 post infusion, with increasing CAR-Ts in pts receiving a higher dose or more robust lymphodepletion (3.4 × 103 ± 2.9 × 103 copies/ug of DNA for DL1-beda vs. 61 × 103 ± 41 × 103 for DL2-benda vs. 49 × 103 ± 16 × 103 for benda/flu). These differences were confirmed by flow cytometry (CD3+CAR+ cells = 13%±9% for DL1-benda vs 21%±10% for DL2-benda vs 35%±8% for benda/flu). There was also improved persistence at wk4 for higher dose and with addition of flu to lymphodepletion (0.06 × 103 ± 0.01 × 103 vs. 0.44 × 103 ± 0.41 × 103 vs. 25 × 103 ± 11 × 103/ug of DNA at wk 4 for DL1-benda, DL2-benda, and benda/flu, respectively). Conclusion CD30.CAR-Ts administered with lymphodepletion with benda/flu are safe and have promising anti-tumor activity for pts with r/r CD30+ lymphomas. A higher dose of CD30.CAR-Ts and the addition of flu to lymphodepletion increased T cell expansion and persistence and translated to improved efficacy.
Purpose Appropriate use of oral chemotherapy is a challenge for patients and clinicians. The purpose of this study was to analyze cancer patients’ use of oral chemotherapies and identify opportunities to improve adherence. Methods We developed a 30-question survey to address frequency and reasons for reducing/skipping doses; sources of information for oral chemotherapy use; perceived importance of food–drug effects; and ease of understanding labeling directions. Results Ninety-three patients taking oral chemotherapies with chronic myeloid leukemia, renal cell carcinoma, breast cancer, and colorectal cancer completed the survey. This was a well-educated population with 69% (n = 62) having completed some college; 51% (n = 47) female and 59% (n = 54) older than 50 years of age. Thirty percent of patients reported forgetting to take their oral chemotherapy at least “sometimes”. Younger patients (<50 vs. ≥50, p = 0.002), shorter treatment duration (<6 vs. ≥6 months p = 0.03), or with chronic myeloid leukemia (vs. other diagnoses, p = 0.015) forget to take their oral chemotherapy at higher rates. Twenty-three percent (n = 21) indicated they intentionally skipped their oral chemotherapies and 38% (n = 8) of those did not inform their physicians. Forty-one percent (n = 28) taking drugs with significant food–drug effects did not think about their last meal before taking their oral chemotherapy and 80% (n = 55) did not understand the potential interactions. Additionally, 39% (n = 36/92) never looked at labeling and 15% (n = 14/91) had difficulty understanding label directions. Conclusion There are three main barriers associated with appropriate use of oral chemotherapies: misunderstanding about the timing of drug with food; stopping drug without informing physicians; and difficulty understanding labeling directions. A multipronged approach is needed to optimize communication of directions for optimal oral chemotherapy use.
between 7 and 21 hour was 50 h 16 min. The mean professional time on Saturday is 6 hours. There was no difference between paediatricians working in a regional or in an university hospital. Work profile of Belgian paediatricians in regional and university hospitals. Philippe Alliet1, Gaston Verellen1, Marc Alexander1, Denise Deliege2, Caroline Artoisenet2. 1Belgian Academy of Paediatrics and 2School of Public Health, University of Louvain (UCL), Belgium
Thrombocytopenia is commonly seen in laboratory findings, especially in critically ill patients. Although the incidence is rare, drug-induced immune thrombocytopenia (DITP) is a serious complication that is often overlooked as a cause of thrombocytopenia. Over the last century, extensive research and data collection have been done in an attempt to better characterize DITP. Heparin-induced thrombocytopenia is the most common DITP and has distinct pathogenesis, diagnosis, and treatment options. However, other offending medications are less well known and have triggered many questions and constant search for answers. This review will discuss both drug-induced immune-mediated and nonimmune-mediated thrombocytopenias, with a focus on immune-mediated processes. Thrombocytopenia caused by chemotherapy will not be discussed in this article.
