Patient-reported outcomes in CD30-directed CAR-T cells against relapsed/refractory CD30+ lymphomas

Chimeric antigen receptor (CAR)-T cells targeting CD30 have demonstrated high response rates with durable remissions observed in a subset of patients with relapsed/refractory CD30+ hematologic malignancies, particularly classical Hodgkin lymphoma. This therapy has low rates of toxicity including cytokine release syndrome with no neurotoxicity observed in our phase 2 study. We collected patient-reported outcomes (PROs) on patients treated with CD30 directed CAR-T cells to evaluate the impact of this therapy on their symptom experience. We collected PROs including PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health and Physical Function questionnaires and selected symptom questions from the NCI PRO-CTCAE in patients enrolled on our clinical trial of CD30-directed CAR-T cells at procurement, at time of CAR-T cell infusion, and at various time points post treatment. We compared PROMIS scores and overall symptom burden between pre-procurement, time of infusion, and at 4 weeks post infusion. At least one PRO measurement during the study period was found in 23 out of the 28 enrolled patients. Patient overall symptom burden, global health and mental health, and physical function were at or above baseline levels at 4 weeks post CAR-T cell infusion. In addition, PROMIS scores for patients who participated in the clinical trial were similar to the average healthy population. CD30 CAR-T cell therapy has a favorable toxicity profile with patient physical function and symptom burden recovering to at least their baseline pretreatment health by 1 month post infusion. Trial registration number: NCT02690545

Pretherapy metabolic tumor volume is associated with response to CD30 CAR T cells in Hodgkin lymphoma

Our group has recently demonstrated that chimeric antigen receptor T-cell therapy targeting the CD30 antigen (CD30.CAR-T) is highly effective in patients with relapsed and refractory (r/r) classical Hodgkin lymphoma (cHL). Despite high rates of clinical response, relapses and progression were observed in a subset of patients. The objective of this study was to characterize clinical and correlative factors associated with progression-free survival (PFS) after CD30.CAR-T cell therapy. We evaluated correlatives in 27 patients with r/r cHL treated with lymphodepletion and CD30.CAR-T cells. With a median follow-up of 9.5 months, 17 patients (63%) progressed, with a median PFS of 352 days (95% confidence interval: 116-not reached), and 2 patients died (7%) with a median overall survival of not reached. High metabolic tumor volume (MTV, .60 mL) immediately before lymphodepletion and CD30.CAR-T cell infusion was associated with inferior PFS (log rank, P 5 .02), which persisted after adjusting for lymphodepletion and CAR-T dose (log rank, P 5 .01 and P 5 .006, respectively). In contrast, receiving bridging therapy, response to bridging therapy, CD30.CAR-T expansion/persistence, and percentage of CD31PD-11 lymphocytes over the first 6 weeks of therapy were not associated with differences in PFS. In summary, this study reports an association between high baseline MTV immediately before lymphodepletion and CD30.CAR-T cell infusion and worse PFS in patients with r/r cHL

Determination of in vitro antidiabetic effects of Zingiber officinale Roscoe

Aqueous extracts of Zingiber officinale rhizomes were studied to evaluate their antidiabetic effects on protein glycation and on the diffusion of glucose in vitro in the present study. Zingiber officinale rhizome aqueous extract were examined at concentrations of 5, 10, 20 and 40 g/L. The antidiabetic effects were found to be dose-dependent. Antidiabetic potential of Zingiber officinale was mainly through inhibition of the glucose diffusion and to a limited extent by reducing the glycation. However, further studies are needed to determine in vitro effects of therapeutic potential by restraining postprandial glucose absorptions and plasma protein glycations in diabetic subjects.Extratos aquosos de rizomas Zingiber officinale foram estudados para avaliar os seus efeitos antidiabéticos em glicação de proteínas e sobre a difusão de glicose in vitro, no presente estudo. Extratos aquosos de Zingiber officinale foram examinados nas concentrações de 5, 10, 20 e 40 g extrato de planta/L. Os efeitos antidiabéticos observados eram dependentes da dose. O potencial antidiabético de Zingiber officinale se verificou, principalmente, através da inibição da difusão de glicose e, em menor extensão, através da redução da glicação. Estudos adicionais são necessários para elucidar se efeitos in vitro representam potencial terapêutico, restringindo a absorção de glicose pós-prandial e a glicação de proteínas plasmáticas em indivíduos diabéticos

Best herbs for managing diabetes: a review of clinical studies

Diabetes mellitus is a public health problem which leads to serious complications over time. Experimentally, many herbs have been recommended for treating diabetes. In most cases, however, the recommendations are based on animal studies and limited pieces of evidence exist about their clinical usefulness. This review focused on the herbs, the hypoglycemic actions of which have been supported by three or more clinical studies. The search was done in Google Scholar, Medline and Science Direct databases using the key terms diabetes, plants, herbs, glucose and patients. According to the clinical studies, Aegle marmelos, Allium cepa, Gymnema sylvestre, Momordica charantia, Ocimum sanctum, Nigella sativa, Ocimum sanctum, Panax quinquefolius, Salacia reticulate, Silybum marianum and Trigonella foenum-graecum have shown hypoglycemic and, in some cases, hypolipidemic activities in diabetic patients. Among them, Gymnema sylvestre, Momordica charantia, Silybum marianum and Trigonella foenum-graecum have acquired enough reputation for managing diabetes. Thus, it seems that physicians can rely on these herbs and advise for the patients to improve management of diabetes

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Use of simple hematological, biochemical and clinical parameters to monitor response of multiple myeloma patients on high dose thalidomide therapy

BACKGROUND: Evidence of increased bone marrow vascularity in multiple myeloma (MM) has led to the use of anti-angiogenic drugs especially thalidomide in relapsed or refractory patients. Currently, parameters such as serum/ urine electrophoresis for M (monoclonal) proteins, bone marrow biopsy with touch preparation and b2 microglobulin are routinely used to assess response to therapy. These investigations are expensive, invasive and require high technical setup. AIM: To correlate simple and routine hematological and biochemical parameters with the key marker of disease i.e. M proteins. SETTINGS AND DESIGN: This is an open label, uncontrolled, single-arm study. MATERIALS AND METHODS: Twenty nine refractory or relapsed multiple myeloma patients of both sexes (M=20, F=9) with age ranging between 35-72 years were initiated on 200 mg/day of thalidomide with fortnightly increments of 200 mg to a maximum tolerated dose not exceeding 800 mg/day. All hematological and biochemical parameters were monitored at monthly intervals for one year. STATISTICAL ANALYSIS: Correlation analysis was performed between hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophil count (ANC), platelet count (PC), total proteins (TP), serum albumin and serum globulin on one hand and M protein levels on the other using Pearsons Correlation test by SPSS version 7.5. RESULT: Hb, TLC, ANC, PC and serum albumin levels showed a significant negative correlation with M proteins. A highly significant positive correlation existed between M proteins on one hand and TP and globulin levels on the other. Dryness of skin indicated positive response to therapy. These correlations were found to be significant at the end of one month of therapy in all the above-mentioned parameters except in TLC where it was significant after 2 months of thalidomide therapy. CONCLUSION: Results suggest that sustained efficacy of thalidomide therapy may be amenable to monitoring by these simple, inexpensive and easily available investigations after ascertaining an initial response by M protein and marrow plasmacytosis as these parameters closely follow M protein levels. However more studies are required to further substantiate these findings