Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma.

Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy for which no standard treatment exists. MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation. We conducted a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of ibrutinib in previously treated MZL.

Long-term follow up of rates of secondary malignancy and late relapse of two trials using radioimmunotherapy consolidation following induction chemotherapy for previously untreated indolent lymphoma.

Existing data suggest that myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) peak in incidence 5-10 years following exposure to ionizing radiation, while most publications report less than 5 years of follow-up after radioimmunotherapy (RIT). We report the rate of secondary MDS/AML among 60 patients treated with two front-line sequential chemotherapy-RIT trials with over 11 years of follow-up. Among 35 patients evaluated after fludarabine-RIT and 25 patients evaluated after CVP (cyclophosphamide, vincristine, prednisone)-RIT treatment, the crude, cumulative and Kaplan-Meier rates of MDS/AML at 11 years of follow-up from the combined trials were 0.

Extracorporeal membrane oxygenation as a bridge to chemotherapy in an Orthodox Jewish patient.

Objective: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiopulmonary support offers survival possibilities to patients who otherwise would succumb to cardiac failure. Often referred to as "a bridge to recovery," involving a ventricular assist device or cardiac transplantation, this technology only affords temporary cardiopulmonary support. Physicians may have concerns about initiating VA-ECMO in patients who, in the absence of recovery or transfer to longer-term therapies, might assert religious or cultural objections to the terminal discontinuation of life-sustaining therapy (LST).

Lenalidomide inhibits lymphangiogenesis in preclinical models of mantle cell lymphoma.

Lymphomas originate in and spread primarily along the lymphatic system. However, whether lymphatic vessels contribute to the growth and spreading of lymphomas is largely unclear. Mantle cell lymphoma (MCL) represents an aggressive non-Hodgkin's lymphoma.

Metronomic therapy for refractory/relapsed lymphoma: the PEP-C low-dose oral combination chemotherapy regimen.

Background: Metronomic therapy is the application of continuous, low dose chemotherapy. The doses of chemotherapy are usually not sufficient to destroy neoplastic cells, but impact the milieu, particularly angiogenesis.

Objective: To determine if the oral PEP-C regimen, consisting of prednisone 20 mgm, etoposide 50 mgm, procarbazine 50 mgm, and cyclophosphamide 50 mgm given in either a daily, alternate day, or fractionated basis, is effective in a variety of lymphomas.

Bortezomib in combination with rituximab, dexamethasone, ifosfamide, cisplatin and etoposide chemoimmunotherapy in patients with relapsed and primary refractory diffuse large B-cell lymphoma.

Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER).

Antiangiogenic therapies in non-Hodgkin's lymphoma.

The tumor microenvironment is critical in the initiation and progression of cancerous growth, which is dependent on the establishment of a functional vascular network supporting neoplastic proliferation. While the precise role of tumor angiogenesis in lymphoma pathogenesis remains under active investigation, emerging data on the proangiogenic properties of the neoplastic lymphoma cells and mechanism of vascular assembly suggest that angiogenesis is highly relevant to the biology and therapy of non-Hodgkin's lymphoma. Antiangiogenic therapies in non-Hodgkin's lymphoma are in various stages of clinical development aiming at distinct angiogenic pathways operative in endothelial cells and perivascular stromal cells.

A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254.

Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation.

Novel agents for follicular lymphoma.

Unlabeled and radiolabeled anti-CD20 monoclonal antibodies have had a significant impact in the care of patients with follicular lymphoma (FL) over the past decade. More recently, bendamustine has demonstrated activity in refractory FL, and has been explored as initial therapy and in novel combinations. Whereas outcomes for this patient population have significantly improved, there remains substantial unmet need for patients who require more effective and better-tolerated therapies.

Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma.

Purpose: The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).

Patients And Methods: Seventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.

Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma.

Background: Bortezomib has preclinical and clinical in B-cell lymphomas, both alone and in combination with other agents. A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL).

Methods: Twenty patients (16 with DLBCL and 4 with MCL) with a median age of 66 years (range, 29-84 years) were enrolled.

Response to second-line therapy defines the potential for cure in patients with recurrent diffuse large B-cell lymphoma: implications for the development of novel therapeutic strategies.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) who are not cured by initial therapy sometimes experience disease-free survival after autologous stem cell transplantation. Chemotherapy responsiveness before transplantation is a major predictor of outcome. Patients not responding to second-line regimens may receive third-line therapy in the hopes of achieving response, but outcome data are limited.

Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma.

Background: Targeting the tumor microenvironment and angiogenesis is a novel lymphoma therapeutic strategy. The authors report safety, activity, and angiogenic profiling results with the rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide (RT-PEPC) regimen in patients with recurrent mantle cell lymphoma (MCL).

Methods: RT-PEPC included induction (Months 1-3) of rituximab 4 times weekly, daily thalidomide (50 mg), and PEPC followed by maintenance thalidomide (100 mg), oral PEPC titrated to the neutrophil count, and rituximab every 4 months.

Mantle cell lymphoma: biological insights and treatment advances.

Mantle cell lymphoma (MCL) exhibits considerable molecular heterogeneity and complexity, and is regarded as one of the most challenging lymphomas to treat. With increased understanding of the pathobiology of MCL, it is proposed that MCL is the result of 3 major converging factors, namely, deregulated cell cycle pathways, defects in DNA damage responses, and dysregulation of cell survival pathways. In the present era of targeted therapies, these biologic insights have resulted in the identification of several novel rational targets for therapeutic intervention in MCL that are undergoing active clinical testing.

Management of relapsed mantle cell lymphoma: still a treatment challenge.

Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that remains incurable, and is associated with a median survival of approximately 5 years. Management of patients with relapsed or refractory disease is challenging. The major therapeutic goal in MCL management is to improve survival and quality of life whenever possible.

Durable complete remissions in HIV-associated Hodgkin lymphoma after treatment with only one cycle of chemotherapy complicated by sepsis.

The infiltration of nonmalignant cells surrounding the Reed-Sternberg cells within the tumors of Hodgkin lymphoma (HL) might be central to the pathophysiology of the disease. Severe sepsis results in a flood of cytokines that activate the immune system and is associated with generalized lymphocyte apoptosis. We report on 2 patients with HIV infection and HL who achieved durable complete remissions following only one cycle of chemotherapy that was complicated by neutropenic sepsis.

Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma.

Angiogenesis, the growth of new blood vessels, requires dynamic expansion, assembly and stabilization of vascular endothelial cells in response to proangiogenic stimuli. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. While many aspects of postnatal pathological angiogenesis have been extensively studied in the context of nonhematopoietic neoplasms, the precise role of these processes in lymphoma pathogenesis is under active investigation.

Milatuzumab: a promising new agent for the treatment of lymphoid malignancies.

Background: Non-Hodgkin's lymphoma and multiple myeloma are often incurable and respond to a limited set of treatment options. The selective expression of CD74, the invariant chain of the MHC class II molecule, in these malignancies provides an attractive target for antibody-based therapy.

Objective: This review evaluates the preclinical data for milatuzumab, a humanized antibody targeting CD74, as a treatment for non-Hodgkin's lymphomas and multiple myeloma.

Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma.

Background: In this international, multicenter trial, the authors evaluated rituximab (anti-CD20) plus epratuzumab (anti-CD22) in patients with postchemotherapy relapsed/refractory, indolent non-Hodgkin lymphoma (NHL), including long-term efficacy.

Methods: Forty-nine patients with follicular NHL (FL) (N = 41) or small lymphocytic lymphoma (SLL) (N = 7) received intravenous epratuzumab 360 mg/m2 and then intravenous rituximab 375 mg/m2 weekly x4. The regimen was tolerated well.

Targeted treatment and new agents in diffuse large B-cell lymphoma.

The concurrent use of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has established the utility of chemoimmunotherapy for the treatment of aggressive non-Hodgkin's lymphoma (NHL). However, a substantial number of patients with diffuse large B-cell lymphoma (DLBCL) still die from their disease, and improvements in therapy remain necessary. Numerous efforts have been made to improve prognostic tools in DLBCL, including the International Prognostic Index (IPI).

Optimizing the treatment of patients with rituximab-pretreated recurrent indolent non-Hodgkin lymphoma.

Indolent non-Hodgkin lymphomas (NHLs) are among the most prevalent hematologic malignancies; their incidence has been increasing over the last several decades. Because advanced-stage indolent lymphoma is generally incurable, therapy for this group of patients is geared toward chronic management over years. Recently, numerous trials have demonstrated that the combination of chemotherapy and the anti-CD20 monoclonal antibody rituximab can provide superior efficacy to chemotherapy alone.

Combined PET and low-dose, noncontrast CT scanning obviates the need for additional diagnostic contrast-enhanced CT scans in patients undergoing staging or restaging for lymphoma.

Background: Positron emission tomography (PET) is more accurate than computed tomography (CT) in staging and restaging of lymphoma, but both are considered necessary. Increasingly, PET is carried out with a low-dose CT scan. Many patients undergo both PET/CT and standard diagnostic CT.