Phase II Trial of Nivolumab Plus Doxorubicin, Vinblastine, Dacarbazine as Frontline Therapy in Older Adults With Hodgkin Lymphoma.

Purpose: We conducted a phase I/II study evaluating nivolumab plus doxorubicin, vinblastine, dacarbazine (N-AVD) as frontline therapy for treatment-naïve older adults (OA) with classical Hodgkin lymphoma (cHL; ClinicalTrials.gov identifier: NCT03033914).

Methods: Patients age ≥60 years with newly diagnosed, any stage, cHL were treated with six cycles of AVD at standard doses plus nivolumab 240 mg intravenously once every 2 weeks (on days 1 and 15) of each cycle.

Zanubrutinib, Obinutuzumab, and Venetoclax for First-Line Treatment of Mantle Cell Lymphoma with a TP53 Mutation.

TP53-mutant mantle cell lymphoma (MCL) is associated with poor survival outcomes with standard chemoimmunotherapy. Dual BTK and BCL2-inhibition with or without anti-CD20 monoclonal antibody therapy has shown promising activity in TP53-mutant MCL. We conducted a multi-center phase 2 study of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in untreated MCL patients with TP53 mutation.

Matched control analysis suggests that R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared with R-CHOP.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that patients with nongerminal center B-cell like (non-GCB) have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation.

Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma.

Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57-69]).

Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities.

Treatment paradigms for B-cell non-Hodgkin lymphomas (B-NHL) have shifted dramatically in the last 2 decades following the introduction of highly active immunotherapies such as rituximab. Since then, the field has continued to witness tremendous progress with the introduction of newer, more potent immunotherapeutics, including chimeric antigen receptor T-cell therapy, which have received regulatory approval for and currently play a significant role in the treatment of these diseases. Bispecific antibodies (BsAb) are a novel class of off-the-shelf T-cell redirecting drugs and are among the most promising immunotherapeutics for lymphoma today.

Validation of POD24 as a robust early clinical end point of poor survival in FL from 5225 patients on 13 clinical trials.

Observational studies and stand-alone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of patients with FL in the pre- and postrituximab eras to identify clinical factors that predict POD24. Logistic regression models evaluated the association between clinical factors and POD24.

Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions.

Prephase rituximab/prednisone therapy and aging-related, proinflammatory cytokine milieu in older, vulnerable patients with newly diagnosed diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) predominantly affects older adults with suboptimal therapeutic outcomes due to increased treatment-related mortality and toxicities in vulnerable patients, clinically defined by geriatric impairments such as functional limitation, multimorbidity, or cognitive deficits. In this prospective pilot study, we evaluated a rituximab/prednisone prephase treatment strategy in 33 older, vulnerable patients with newly diagnosed DLBCL, defined by either age ≥70 years or age 60-70 years with Karnofsky performance scale (KPS) <80. A single dose of rituximab 375 mg/m2 between 3-10 days and oral prednisone for at least 5 days prior to the first dose of chemoimmunotherapy was administered.

Outcomes of older patients with follicular lymphoma using individual data from 5922 patients in 18 randomized controlled trials.

Limited data exist to describe the clinical features and outcomes for elderly patients with follicular lymphoma (FL). The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group performed a prospectively planned pooled analysis of individual patient data from first-line randomized controlled trials (RCTs) and examined associations between age (≤70 vs >70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (>70 years).

A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma.

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles.

BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis.

Introduction: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts.

Patients And Methods: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells.

Mutational landscape of gray zone lymphoma.

The mutational landscape of gray zone lymphoma (GZL) has not yet been established, and differences from related entities are largely unknown. Here, we studied coding sequence mutations of 50 Epstein-Barr virus (EBV)-negative GZLs and 20 polymorphic EBV+ diffuse large B-cell lymphoma (DLBCL) not otherwise specified (poly-EBV-L) in comparison with classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and DLBCL. Exomes of 21 GZL and 7 poly-EBV-L cases, along with paired constitutional DNA, were analyzed as a discovery cohort, followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases.

Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study.

Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701).

Patient-reported long-term quality of life after tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma.

The JULIET phase 2 trial evaluated a single infusion of tisagenlecleucel in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The objective of the current analysis was to evaluate patient-reported health-related quality of life (HRQoL) with a median follow-up of 19.3 months among patients infused with a single dose of tisagenlecleucel.

Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study.

Background: Lenalidomide plus rituximab is approved to treat patients with relapsed or refractory follicular lymphoma. Obinutuzumab has been shown to enhance antibody-dependent cellular cytotoxicity, phagocytosis, and direct B-cell killing better than rituximab. Our aim was to determine the activity and safety of lenalidomide plus obinutuzumab in previously treated patients with relapsed or refractory follicular lymphoma.

Treatment of aggressive B-cell non-Hodgkin lymphoma beyond frontline therapy in patients not eligible for stem cell transplantation: a structured review.

Aggressive B-cell non-Hodgkin lymphoma (aNHL) accounts for ∼50% of all NHL cases. The only potentially curative, broadly available treatment for patients with relapse, failing frontline treatment, is high-dose therapy followed by autologous stem cell transplantation (ASCT); patients ineligible for/who have failed ASCT have limited standard-of-care options. We conducted a structured review of treatments for relapsed/refractory patients with aNHL based on literature published between 2006 and 2017.

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma.

Background: Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.

Methods: We conducted this multicenter, international, phase 3 superiority trial to evaluate rituximab plus lenalidomide, as compared with rituximab plus chemotherapy, in patients with previously untreated follicular lymphoma.

Diagnosis-to-Treatment Interval Is an Important Clinical Factor in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Has Implication for Bias in Clinical Trials.

Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosis-to-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States.