Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas.

The PI3K/Akt/mTOR (PAM) axis is constitutively activated in multiple lymphoma subtypes and is a promising therapeutic target. The mTOR inhibitor temsirolimus (TEM) and the immunomodulatory agent lenalidomide (LEN) have overlapping effects within the PAM axis with synergistic potential. This multicenter phase I/II study evaluated combination therapy with TEM/LEN in patients with relapsed and refractory lymphomas.

Phase 1b/2 study of ibrutinib and lenalidomide with dose-adjusted EPOCH-R in patients with relapsed/refractory diffuse large B-cell lymphoma.

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is difficult to cure; non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) DLBCL have worse outcomes than GCB DLBCL. Ibrutinib and lenalidomide are synergistic in vitro in ABC DLBCL and may augment salvage chemotherapy. In part 1 of this phase 1b/2 study (NCT02142049), patients with relapsed/refractory DLBCL received ibrutinib 560 mg and escalating doses of lenalidomide on Days 1-7 with DA-EPOCH-R (Days 1-5) in 21-day cycles.

A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China.

The second-generation proteasome inhibitor carfilzomib produces superior outcomes in relapsed or refractory multiple myeloma (MM). We conducted a single-arm trial of twice-weekly carfilzomib (27 mg/m)-dexamethasone (Kd27) for relapsed and refractory MM in China. Kd27 was administered in 28-day cycles to 123 patients previously treated with ≥ 2 other regimens, including treatment with bortezomib and an immunomodulatory drug, and refractory to their most recent therapy.

A phase 1b study of once-weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.

Twice-weekly carfilzomib with lenalidomide-dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once-weekly carfilzomib with Rd (once-weekly KRd) in NDMM patients. The NDMM patients were enrolled regardless of transplant eligibility.

Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups.

Introduction: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up.

Patients And Methods: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd.

Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study.

Twice-weekly carfilzomib (27 mg/m ) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m ) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles.

Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR.

In ENDEAVOR, carfilzomib (56 mg/m) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a post hoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to <50 mL/min, n = 85 and n = 99; CrCL 50 to <80 mL/min, n = 186 and n = 177; and CrCL ≥80 mL/min, n = 193 and n = 189 for Kd56 and Vd arms, respectively).

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

Background: The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups.

A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2).

Introduction: This phase 1b study evaluated the safety and efficacy of 3 dose levels of carfilzomib when provided with fixed dose oral cyclophosphamide and dexamethasone (KCyd) in patients with newly diagnosed multiple myeloma (MM).

Patients And Methods: CHAMPION-2 was a multicenter single-arm study. Patients with newly diagnosed secretory MM were enrolled and received KCyd treatment for up to 8 cycles.

Death-associated Protein Kinase-1 Expression and Autophagy in Chronic Lymphocytic Leukemia Are Dependent on Activating Transcription Factor-6 and CCAAT/Enhancer-binding Protein-β.

Expression of DAPK1, a critical regulator of autophagy and apoptosis, is lost in a wide variety of tumors, although the mechanisms are unclear. A transcription factor complex consisting of ATF6 (an endoplasmic reticulum-resident factor) and C/EBP-β is required for the IFN-γ-induced expression of DAPK1 IFN-γ-induced proteolytic processing of ATF6 and phosphorylation of C/EBP-β are obligatory for the formation of this transcriptional complex. We report that defects in this pathway fail to control growth of chronic lymphocytic leukemia (CLL).

Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways.

Demyelination as a harbinger of lymphoma: a case report and review of primary central nervous system lymphoma preceded by multifocal sentinel demyelination.

Background: Primary central nervous system lymphoma (PCNSL) may rarely be preceded by "sentinel demyelination," a pathologic entity characterized by histologically confirmed demyelinating inflammatory brain lesions that mimic multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Interpreting the overlapping radiologic and clinical characteristics associated with each of these conditions-contrast-enhancing demyelination of white matter and relapsing and remitting steroid-responsive symptoms respectively-can be a significant diagnostic challenge.

Case Presentation: We describe a 57-year-old woman with an unusual clinical course who presented with multi-focal enhancing white matter lesions demonstrated to be inflammatory demyelination by brain biopsy.

Optimizing Management of Patients with Adult T Cell Leukemia-Lymphoma.

Adult T cell leukemia-lymphoma is a rare disease with a high mortality rate, and is challenging for the clinician. Early allogeneic stem cell transplant can confer durable remission. As novel therapeutic agents become available to treat T cell malignancies, it is increasingly important that medical oncologists, hematologists, and hematopathologists recognize and accurately diagnose adult T cell leukemia-lymphoma.

Giant Cell Tumor of the Tendon Sheath With Discordant Metabolism as a False Positive on Staging of Mantle Cell Lymphoma.

A baseline F-FDG PET/CT scan in a patient with mantle cell lymphoma showed diffuse minimally FDG-avid lymphadenopathy and splenomegaly. There was also a focus of uptake in the left subscapularis muscle without a CT correlate. A post-chemotherapy scan showed interval decrease in size, and resolution of FDG uptake, of the lymph nodes and spleen.

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy.

BCR-ABL inhibitors administered in conjunction with chemotherapy have significantly improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on risks to the fetus are limited. We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data.

Invariant natural killer T cells generated from human adult hematopoietic stem-progenitor cells are poly-functional.

Invariant natural killer T (iNKT) cells constitute an important subset of T cells that can both directly and indirectly mediate anti-tumor immunity. However, cancer patients have a reduction in both iNKT cell number and function, and these deficits limit the potential clinical application of iNKT cells for cancer therapy. To overcome the problem of limited iNKT cell numbers, we investigated whether iNKT cells can be generated in vitro from bone marrow-derived adult hematopoietic stem-progenitor cells (HSPC).

FDG uptake in liposclerosing myxofibrous tumor causes upstaging of Hodgkin lymphoma.

A 22-year-old woman with Hodgkin lymphoma underwent a staging 18F-FDG PET/CT scan, which showed an intense uptake in the right proximal femur, in addition to FDG-avid mediastinal and cervical lymph nodes. The patient thus was diagnosed with stage IV lymphoma with bone marrow involvement. Postchemotherapy restaging scan showed complete resolution of nodal uptake but persistent activity in the right femur.

NKT Cell Responses to B Cell Lymphoma.

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic.

Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia.

Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement.

The Roles of Radiotherapy and Immunotherapy for the Treatment of Lymphoma.

Lymphoma is rising in incidence and there is a continued need for new and novel therapeutic options. Lymphomas are extremely radiosensitive, but the majority of patients are not candidates for involved field radiation therapy. An intact immune system has a critical role in suppressing lymphomagenesis.