Mantle Cell Lymphoma: Optimal Treatment With Bruton Tyrosine Kinase-Targeted Approaches.

Mantle cell lymphoma (MCL) represents a relatively uncommon, heterogeneous lymphoma associated with limited overall survival. Targeting of the B-cell receptor pathway in relapsed disease with covalent Bruton tyrosine kinase (cBTK) inhibition has been demonstrated to be highly effective with cBTK inhibitor monotherapy, an established standard of care in relapsed MCL. This review summarizes the recent data strongly suggesting a role for the integration of covalent BTK inhibition in the first-line treatment setting, after the recent presentation and publication of multiple phase II and randomized phase II/III clinical trials demonstrating benefit for the addition of cBTK inhibitors first line.

Management of relapsed or refractory large B-cell lymphoma: A British Society for Haematology Guideline.

Time to progression is the strongest predictor of outcome in relapsed diffuse large B-cell lymphoma. Second-line treatment with chimeric antigen receptor (CAR) T-cell therapy is recommended for patients with progression within 12 months of first-line chemoimmunotherapy. In patients with late relapse, platinum-based chemotherapy followed by high-dose chemotherapy with autologous stem cell rescue is recommended.

International consensus statement on diagnosis, evaluation, and research of Richter transformation: the ERIC recommendations.

Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL, has developed consensus recommendations for clinical procedures and future research on this disease.

A 3-week pause versus continued Bruton tyrosine kinase inhibitor use during COVID-19 vaccination in individuals with chronic lymphocytic leukaemia (IMPROVE trial): a randomised, open-label, superiority trial.

Background: Chronic lymphocytic leukaemia is the commonest leukaemia and is associated with profound immunosuppression. Bruton tyrosine kinase inhibitors (BTKi) have revolutionised chronic lymphocytic leukaemia management; however, therapy impairs vaccine-induced immunity. We evaluated whether a 3-week pause of BTKi treatment improved spike protein receptor binding domain (RBD) immunity to SARS-CoV-2 booster vaccination while maintaining disease control.

Clonal relatedness as a prognostic marker in Richter transformation of chronic lymphocytic leukemia: a systematic review.

The disease shift of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL), so-called Richter transformation (RT), is a catastrophic clinical event. Rarely, survival can outperform expectations and accurate prognostication for patients may affect therapeutic choices. To date, prognosis has relied on readily available factors such as TP53 disruption, previous CLL treatment status, and performance score.

Real-world outcomes after discontinuation of covalent BTK inhibitor-based therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

This study described real-world treatment patterns and outcomes among patients with CLL/SLL in the post-cBTKi setting. Included were patients who received at least one cBTKi and subsequent line of therapy (LOT) within the Flatiron Health nationwide electronic health record-derived de-identified database (FHD;  = 1,479) and Optum's de-identified Clinformatics Data Mart Database (CDM;  = 1,020). Frequently observed post-cBTKi treatments in both databases included cBTKi monotherapy (23-30%), anti-CD20 mab monotherapy (∼10%), BCL2i monotherapy (∼9%), BCL2i + anti-CD20 mab (∼9%), cBTKi + BCL2i (∼3%), and cBTKi + anti-CD20 mab (5-7%).

Central nervous system prophylaxis in large B-cell lymphoma: A British Society for Haematology Good Practice Paper.

This Good Practice Paper provides recommendations for the baseline investigation, risk stratification and use of prophylactic interventions for patients with large B-cell lymphoma at risk of central nervous system relapse. Recent evidence which has questioned the role of high-dose methotrexate in this clinical scenario is discussed in detail.

Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy.

Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4 T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively.

Acalabrutinib-based regimens in frontline or relapsed/refractory higher-risk CLL: pooled analysis of 5 clinical trials.

Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts.

Complete response of mantle cell lymphoma with central nervous system involvement at diagnosis with acalabrutinib - Case report.

Central nervous system (CNS) involvement by mantle cell lymphoma (MCL) is rare and portends a poor prognosis. We describe the first patient to have a complete response with front-line treatment with single-agent acalabrutinib for MCL CNS.

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%).

Richter transformation-is there light at the end of this tunnel?

Richter transformation (RT) represents an uncommon (2% to 10%) but feared complication of chronic lymphocytic leukemia (CLL). The disease is characterized by rapid disease kinetics, a high-risk genetic mutational profile, chemoimmunotherapy resistance, and consequent poor survival. The typical overall survival (OS) from the pre-Bruton tyrosine kinase (BTK)/B-cell lymphoma 2 (BCL2) inhibitor CLL era is 6-12 months, and recent series of RT complicating progression on a BTK or BCL2 inhibitor in heavily pretreated relapsed CLL patients suggests an OS of only 3-4 months.

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.

The impact of CHOP versus bendamustine on bone mineral density in patients with indolent lymphoma enrolled in the GALLIUM study.

Standard CHOP treatment includes a high cumulative dose of prednisone, and studies have shown increased fracture risk following CHOP. It is unclear whether reductions in bone mineral density (BMD) are caused by glucocorticoids or by the combination with chemotherapy. Our objective was to determine the effect of obinutuzumab (G)/rituximab (R)-bendamustine versus G/R-CHOP on BMD in follicular lymphoma patients.