Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma.

There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.

A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg/m(2) weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24/34) with 26·5% (9/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21/24) and 3 months in 12·5% (3/24) of patients. The median duration of follow-up was 36 months (range 6-90 months). Of the patients who responded, 50% (12/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6-60 months). Three patients were re-treated with rituximab 375 mg/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.

Update on the World Health Organization classification of peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of lymphoproliferative disorders of postthymic origin. Progress in elucidating the pathobiology and appropriate therapy of these neoplasms has been slow, primarily because of their rarity, but also because until the early 1990s, they were generally grouped together and combined with B-cell lymphomas. It is now understood that most PTCLs are highly aggressive and respond poorly to standard chemo therapy, and thus they have a significantly poorer prognosis than their B-cell counterparts. In 1994, the Revised European and American Lymphoma classification provided the first uniform system to classify lymphoproliferative disorders on the basis of morphology, phenotype, genetics, and clinical features. Since then, the World Health Organization (WHO) has refined this system as additional information has evolved to further elucidate the origin of these neoplasms. More recently, several new distinct and provisional categories in the updated WHO classification have been defined. This review summarizes the changes in the fourth edition of the WHO classification of lymphoid tumors, with particular focus on the aggressive subtypes.

Novel therapies in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders associated with a very poor prognosis. Historically, treatment protocols have been largely based on regimens used to treat aggressive B-cell lymphomas; unfortunately, the efficacy of these regimens has been suboptimal, with most patients experiencing relapse after initial therapy. An improved understanding of the molecular biology, pathogenesis, and progression of these disorders has led to the development of a variety of novel targeted agents that may improve outcomes in patients with PTCLs. The purpose of this review is to focus on these novel agents and the various treatment approaches that are currently being evaluated in PTCLs.

Novel therapies in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders associated with a very poor prognosis. Historically, treatment protocols have been largely based on regimens used to treat aggressive B-cell lymphomas; unfortunately, the efficacy of these regimens has been suboptimal, with most patients experiencing relapse after initial therapy. An improved understanding of the molecular biology, pathogenesis, and progression of these disorders has led to the development of a variety of novel targeted agents that may improve outcomes in patients with PTCLs. The purpose of this review is to focus on these novel agents and the various treatment approaches that are currently being evaluated in PTCLs.