Innovations in Antibody-Drug Conjugate (ADC) in the Treatment of Lymphoma.

Chemoimmunotherapy and cellular therapy are the mainstay of the treatment of relapsed/refractory (R/R) lymphomas. Development of resistance and commonly encountered toxicities of these treatments limit their role in achieving desired response rates and durable remissions. The Antibody-Drug Conjugate (ADC) is a novel class of targeted therapy that has demonstrated significant efficacy in treating various cancers, including lymphomas. To date, three ADC agents have been approved for different lymphomas, marking a significant advancement in the field. In this article, we aim to review the concept of ADCs and their application in lymphoma treatment, provide an analysis of currently approved agents, and discuss the ongoing advancements of ADC development.

Genetic events associated with venetoclax resistance in CLL identified by whole-exome sequencing of patient samples.

Although BCL2 mutations are reported as later occurring events leading to venetoclax resistance, many other mechanisms of progression have been reported though remain poorly understood. Here, we analyze longitudinal tumor samples from 11 patients with disease progression while receiving venetoclax to characterize the clonal evolution of resistance. All patients tested showed increased in vitro resistance to venetoclax at the posttreatment time point. We found the previously described acquired BCL2-G101V mutation in only 4 of 11 patients, with 2 patients showing a very low variant allele fraction (0.03%-4.68%). Whole-exome sequencing revealed acquired loss(8p) in 4 of 11 patients, of which 2 patients also had gain (1q21.2-21.3) in the same cells affecting the MCL1 gene. In vitro experiments showed that CLL cells from the 4 patients with loss(8p) were more resistant to venetoclax than cells from those without it, with the cells from 2 patients also carrying gain (1q21.2-21.3) showing increased sensitivity to MCL1 inhibition. Progression samples with gain (1q21.2-21.3) were more susceptible to the combination of MCL1 inhibitor and venetoclax. Differential gene expression analysis comparing bulk RNA sequencing data from pretreatment and progression time points of all patients showed upregulation of proliferation, B-cell receptor (BCR), and NF-κB gene sets including MAPK genes. Cells from progression time points demonstrated upregulation of surface immunoglobulin M and higher pERK levels compared with those from the preprogression time point, suggesting an upregulation of BCR signaling that activates the MAPK pathway. Overall, our data suggest several mechanisms of acquired resistance to venetoclax in CLL that could pave the way for rationally designed combination treatments for patients with venetoclax-resistant CLL.

The effect of innovative smartphone application on adherence to a home-based exercise programs for female older adults with knee osteoarthritis in Saudi Arabia: a randomized controlled trial.

PURPOSE: To examine the effects of an Arabic smartphone application on adherence to home exercise programs (HEPs) and the effectiveness of mobile-based HEPs on pain, physical function, and lower-limb muscle strength among older women with knee osteoarthritis (OA). MATERIALS AND METHODS: This randomised control trial (ClinicalTrials.gov: (NCT04159883) enrolled 40 women aged ≥50 years with knee OA who were randomised into the app group (experimental; n = 20) receiving HEPs using an Arabic smartphone application called "My Dear Knee", whereas the paper group (control; n = 20) receiving HEPs as hand-outs. Both groups had the same exercise program. Outcome measures were self-reported adherence, changes in the Arabic Numeric Pain Rating Scale, the Arabic version of the reduced Western Ontario, McMaster Universities Osteoarthritis Index-Physical Function subscale, and Five-Times Sit-To-Stand Test scores. All participants were assessed at baseline, at week 3 and week 6. Using completer-only analyses, the repeated measures ANOVA was used to compare the means of the outcome measures between the two groups. RESULTS: At the end of week 6, the app group reported greater adherence to HEPs (p = .002) and significant reduction in pain (p = .015). CONCLUSIONS: A smartphone application with motivational and attractive features could enhance adherence to HEPs in this patient cohort.IMPLICATIONS FOR REHABILITATIONOlder adults with knee OA may face many obstacles that prevent or limit their adherence to the prescribed HEP.Smart device apps supported with attractive and motivational features could be an effective strategy to enhance adherence to HEPs among older adults with knee OA.Using such remote technology appears to overcome the barriers that may limit the ability of older women to receive supervised physical therapy in a clinical setting.