Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial.

Background: Initial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.

Neoadjuvant Immunotherapy and De-escalation of Surgery in Locally Advanced Breast Implant-associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T-cell lymphoma diagnosed in patients with a history of breast implants. Most patients develop a periprosthetic effusion at early stages of disease while less common presentations include a palpable mass, severe capsular contracture, lymphadenopathy, or cutaneous erythema. Due to the complex nature of this disease, a multidisciplinary approach is necessary for optimal management, particularly in locally advanced disease or inoperable patients.

Quality of life in advanced-stage, asymptomatic, non-bulky follicular lymphoma treated with rituximab shows significant improvement compared with watchful-waiting.

Traditionally, patients with asymptomatic, advanced-stage follicular lymphoma were managed with a watchful-waiting approach until disease progression. The 'Watch and Wait' Phase-3 randomised international trial examined whether rituximab could delay the need for treatment and the effect on quality of life (QoL). In this article, we present the long-term results of the QoL aspect of the trial.

Towards an empathic hidden curriculum in medical school: A roadmap.

The "hidden curriculum" in medical school includes a stressful work environment, un-empathic role models, and prioritisation of biomedical knowledge. It can provoke anxiety and cause medical students to adapt by becoming cynical, distanced and less empathic. Lower empathy, in turn, has been shown to harm patients as well as practitioners.

Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study.

Background: Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma.

Methods: This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK).

Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%).

Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience.

Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included.

Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients.

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study.

Background: Obinutuzumab with polatuzumab vedotin or lenalidomide showed tolerability and activity in phase 1b/2 trials that recruited patients with relapsed or refractory follicular lymphoma. We aimed to examine whether the novel polatuzumab vedotin-obinutuzumab-lenalidomide (Pola-G-Len) combination might enhance antitumour response in patients with relapsed or refractory follicular lymphoma.

Methods: This multicentre, single-arm phase 1b/2 study tested Pola-G-Len in patients with relapsed or refractory follicular lymphoma, and polatuzumab vedotin in combination with rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma.

Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial.

The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti-PD-L1) is hypothesized to restore antitumor immunity.

Results of a UK National Cancer Research Institute Phase II study of brentuximab vedotin using a response-adapted design in the first-line treatment of patients with classical Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or comorbidity (BREVITY).

Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was complete metabolic response (CMR) by positron emission tomography/computed tomography after four BV cycles (PET4).

Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery.

High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130).

Kinetics of T-cell subset reconstitution following treatment with bendamustine and rituximab for low-grade lymphoproliferative disease: a population-based analysis.

Delayed lymphocyte and T-cell immune reconstitution following bendamustine-rituximab (BR) for indolent non-Hodgkin lymphoma (iNHL) has been described, but no information is available for chronic lymphocytic leukaemia (CLL). We present a population-based retrospective analysis of immune reconstitution and risk of infection following BR. Outcomes included timing/correlates of CD4+ recovery and risk of ≥grade 3 infections.

Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting.

Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT.

Use of F-fludeoxyglucose positron emission tomography-CT in the management of breast implant-associated anaplastic large cell lymphoma.

The prognosis and preferred management of breast implant-associated anaplastic large cell lymphoma is dependent on whether lymphoproliferative cells are confined to within the fibrous capsule, in an effusion or lining the fibrous capsule, or if there is spread beyond the capsule in the form of a mass lesion. We describe a case where F-fludeoxyglucose positron emission tomography-CT was used to confirm localized disease and guide management decisions.

A Double Hit CD10-Negative B-Cell Lymphoma with t(3;8)(q27;q24) Leading to Juxtaposition of the BCL6 and MYC Loci Associated with Good Clinical Outcome.

The WHO classification of lymphomas allows for a group of diseases that have features intermediate between those of Burkitt lymphoma and diffuse large B-cell lymphoma. These are a diverse group of diseases whose genetics and clinical course are yet to be fully described. We report an unusual case of high grade B-cell lymphoma, intermediate between DLBCL and BL, lacking CD10 expression in which the chromosomal translocation t(3;8)(q27;q24) was found to be the sole chromosomal abnormality.

Enhancement of CD154/IL4 proliferation by the T follicular helper (Tfh) cytokine, IL21 and increased numbers of circulating cells resembling Tfh cells in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) cells encounter T-cells and proliferate in response to T-cell signals in the lymph node microenvironment. In this report we determined interleukin 21 (IL21) function in CLL and showed that IL21 and interleukin 4 (IL4) act co-operatively to promote leukaemic cell proliferation without apoptosis or differentiation We further show that IL21 increased side population (SP) cells, which are associated with resistance to chemotherapy and increased self-renewal capacity in CLL. IL21 and IL4 are the major cytokines produced by the recently described CD4(+) T follicular helper (Tfh) cell subset.

Defining the prognosis of early stage chronic lymphocytic leukaemia patients.

Approximately 70% of chronic lymphocytic leukaemia (CLL) patients present with early stage disease, therefore defining which patients will progress and require treatment is a major clinical challenge. Here, we present the largest study of prognostic markers ever carried out in Binet stage A patients (n = 1154) with a median follow-up of 8 years. We assessed the prognostic impact of lymphocyte doubling time (LDT), immunoglobulin gene (IGHV) mutation status, CD38 expression, ZAP-70 expression and fluorescence in situ hybridization (FISH) cytogenetics with regards to time to first treatment (TTFT) and overall survival (OS).

CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL.

The world of chronic lymphocytic leukemia (CLL) research is awash with prognostic markers. However, very few of the current group play a clearly defined role in the pathology of this disease and even fewer represent a tractable therapeutic target. One such marker that fulfils both of these criteria is the integrin CD49d.