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A randomized trial suggests that patients with negative PET-CT findings after two cycles of ABVD may have the bleomycin dropped from the regimen for the final four cycles. The omission of bleomycin reduced pulmonary toxic effects without reducing overall survival. The treatment of advanced-stage Hodgkin’s lymphoma with chemotherapy has produced high survival rates. A series of randomized trials has confirmed that doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), first described more than 40 years ago, 1 yields cure rates of 70 to 80%, similar to the rates observed with more complex multidrug regimens. 2 – 7 The possible exception is escalated therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), with higher-than-standard doses of etoposide, doxorubicin, and cyclophosphamide. 8 This escalated regimen has been shown to yield higher progression-free survival rates than ABVD among previously untreated patients. 9 , 10 Trials in which ABVD and . . .

A randomized trial comparing ibrutinib plus rituximab with rituximab alone in patients with Waldenström’s macroglobulinemia showed significantly higher rates of progression-free survival and overall response with the addition of ibrutinib.

Follicular lymphoma (FL) is an indolent, germinal center B cell–derived lymphoid neoplasm, for which recent advances in treatment have substantially improved patient survival. However, FL remains an incurable and heterogeneous disease, with groups of patients experiencing early disease progression, histologic transformation, or a high risk of treatment-related toxicity. Additionally, FL is a continually relapsing disease, and response rates and disease-control intervals decrease with each subsequent line of therapy. In this review, we explore the current treatment landscape for relapsed or refractory FL and promising therapies in development, highlighting the efficacy and potential risks of each treatment. We provide a real-world perspective on the unmet needs of patients with FL. Novel therapeutic approaches in development offer a wide array of options for clinicians when treating relapsed or refractory FL. A nuanced approach is required to address the needs of individual patients, taking into consideration both the risks and benefits of each treatment option, as well as patient preferences.

Bruton’s tyrosine kinase inhibitors (BTKi), widely used in Waldenström macroglobulinemia (WM), are known to impair B cell function, but their broader immunological effects remain unclear. We investigated the T cell compartment in patients with WM receiving BTKi, including those who underwent a supervised treatment pause before a third COVID-19 mRNA vaccine dose, as well as treatment naïve controls. Using flow cytometry, antigen-specific T cell assays, and single-cell RNA sequencing, we found that BTKi-treated patients exhibited a reduction in naïve T cells, enrichment of terminal effector CD8⁺ T emra cells, and lower PD-1 expression. Despite poor vaccine-induced RBD-specific memory B cells, CD4⁺ and CD8⁺ T cell responses to SARS-CoV-2 remained detectable, with enhanced CD8⁺ responses to the omicron variant in BTKi-treated individuals. Single-cell transcriptomics revealed an expansion of CD16⁺ CD56⁺ Granzyme B⁺ NK-like CD8⁺ T cells in BTKi-treated patients, which further increased following BTKi interruption. These cells expressed a potent cytotoxic and NK-like transcriptional phenotype. Our findings identify a novel off-target effect of BTKi therapy: expansion of cytotoxic NK-like CD8⁺ T cells, with implications for immune monitoring and vaccine responsiveness in BTKi-treated patients.

Patients with Waldenström macroglobulinaemia (WM) are at increased risk of severe COVID‐19 infection and have poor immune responses to COVID‐19 vaccination. This study assessed whether a closely monitored pause in Bruton's Tyrosine Kinase inhibitor (BTKi) therapy might result in an improved humoral response to a 3rd COVID‐19 vaccine dose. Improved response was observed in WM patients who paused their BTKi, compared to a group who did not pause their BTKi. However, the response was attenuated after BTKi recommencement. This data contributes to our understanding of vaccination strategies in this patient group and may help inform consensus approaches in the future.

Background The single‐arm DAWN trial (NCT01779791) of ibrutinib monotherapy in patients with relapsed/refractory follicular lymphoma (FL) showed an overall response rate (ORR) of 20.9% and a median response duration of 19.4 months. This biomarker analysis of the DAWN dataset sought to determine genetic classifiers for prediction of response to ibrutinib treatment. Methods Whole exome sequencing was performed on baseline tumor samples. Potential germline variants were excluded; a custom set of 1216 cancer‐related genes was examined. Responder‐ versus nonresponder‐associated variants were identified using Fisher's exact test. Classifiers with increasing numbers of genes were created using a greedy algorithm that repeatedly selected genes, adding the most nonresponders to the existing “predicted nonresponders” set and were evaluated with 10‐fold cross‐validation. Results Exome data were generated from 88 patient samples and 13,554 somatic mutation variants were inferred. Response data were available for 83 patients (17 responders, 66 nonresponders). Each sample showed 100 to >500 mutated genes, with greater variance across nonresponders. The overall variant pattern was consistent with previous FL studies; 75 genes had mutations in >10% of patients, including genes previously reported as associated with FL. Univariate analysis yielded responder‐associated genes FANCA, HISTH1B, ANXA6, BTG1, and PARP10, highlighting the importance of functions outside of B‐cell receptor signaling, including epigenetic processes, DNA damage repair, cell cycle/proliferation, and cell motility/invasiveness. While nonresponder‐associated genes included well‐known TP53 and CARD11, genetic classifiers developed using nonresponder‐associated genes included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting resistance to ibrutinib may be related to broad biological functions connected to epigenetic modification, telomere maintenance, and cancer‐associated signaling pathways (mTOR, JAK/STAT, NF‐κB). Conclusion The results from univariate and genetic classifier analyses provide insights into genes associated with response or resistance to ibrutinib in FL and identify a classifier developed using nonresponder‐associated genes, which warrants further investigation. Trial registration: NCT01779791. Using patient samples from the single‐arm DAWN trial (NCT01779791), we performed univariate and genetic classifier analyses to gain insights into genes associated with response (responders, n = 17) or lack of response (nonresponders, n = 66) to ibrutinib monotherapy in relapsed/refractory follicular lymphoma. Genetic classifiers were developed using nonresponder‐associated genes, and the top five genes associated with no response to ibrutinib included ATP6AP1, EP400, ARID1A, SOCS1, and TBL1XR1, suggesting that resistance to ibrutinib might be related to broad biological functions outside Bruton tyrosine kinase signaling.

The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed. Landmark analyses of progression‐free survival (PFS) and overall survival (OS) by end of treatment (EOT) and end of induction (EOI) response status according to RECIL 2017 and Lugano 2014 criteria, and prognostic value of response at EOT/EOI were also compared. Overall, 1333 patients were included from GOYA and 502 from GALLIUM. Complete response (CR) status according to RECIL 2017 criteria showed high concordance with complete metabolic response (CMR) status by Lugano 2014 criteria in both GOYA (92.5%) and GALLIUM (92.4%). EOT and EOI CR/CMR status by both criteria was highly prognostic for PFS in GOYA (RECIL 2017 [CR]: hazard ratio [HR], 0.35 [95% confidence interval [CI] 0.26–0.46]; Lugano 2014 [CMR]: HR, 0.35 [95% CI 0.26–0.48]; both p  < .0001) and GALLIUM (RECIL 2017 [CR]: HR, 0.35 [95% CI 0.23–0.53]; Lugano 2014 [CMR]: HR, 0.21 [95% CI 0.14–0.31]; both p  < .0001). In conclusion, response categorization by RECIL 2017 is similar to that by Lugano 2014 criteria, with high concordance observed. Both were prognostic for PFS and OS.

A trial involving 523 patients with mantle-cell lymphoma randomly assigned patients to receive bendamustine plus rituximab or these drugs plus ibrutinib. At a median follow-up of 7 years, the median progression-free survival with ibrutinib was nearly 81 months, as compared with 53 months without ibrutinib.

Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p<0·0001). Grade 3–4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.

Whereas 79% (range 50–100%) of articles included at least one male author, only 45% (7–78%) included at least one female author. 55% of the analysed articles were written exclusively by men, whereas 21% were all-women. [...]only 12% of review articles, arguably the most authoritative articles and where editorial preferences exert strong influence, were written exclusively by women compared with 42% all-men authorship. In one journal, a single female author (of a review) was included over the 5-year study period (among 30 total authors). WiL remain committed to reporting the data and supporting evidence-based strategies to reduce unconscious bias and achieve gender parity in all aspects of academia.6 Evidence-based approaches that can change these outcomes include: recognising that implicit (and explicit) attitudes and beliefs can decrease bias over time, developing role-based transparent policies and selection processes, and tracking inclusion data for editorial positions and all assignments of published articles.7–9 We appreciate the attention of editorial boards to this important issue and are committed to working collaboratively towards gender equity in the near future.