Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.
Lenalidomide is clinically active in patients with relapsed or refractory B-CLL. These findings are encouraging and warrant further investigation of this agent in the treatment of this disorder.
NEDD8 activating enzyme (NAE) has been identified as an essential regulator of the NEDD8 conjugation pathway, which controls the degradation of many proteins with important roles in cell-cycle progression, DNA damage, and stress responses. Here we report that MLN4924, a novel inhibitor of NAE, has potent activity in acute myeloid leukemia (AML) models.
This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenströ m Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m 2 on days 1, 8, 15, q 28 days 3 6 cycles, and rituximab 375 mg/m 2 weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% CI: 70-98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% CI: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM. Am. J. Hematol. 85:670-674, 2010. V
IntroductionIncorporation of CD20 monoclonal antibody (mAb) has significantly advanced treatment for patients with chronic lymphocytic leukemia (CLL). Improved outcomes were demonstrated with the addition of the CD20 mAb rituximab to fludarabine-based therapy, both in frontline and relapsed settings, 1-5 including improved overall survival (OS) in the frontline setting with combined fludarabine, cyclophosphamide, and rituximab (FCR). 5 Monotherapy with standard dose and schedule of rituximab has limited efficacy, especially in relapsed/refractory CLL. 6,7 A large number of patients in the United States receive rituximab either as monotherapy or in combination with fludarabine-based chemotherapy in both frontline and relapsed/refractory settings 8 ; refractoriness to CD20 mAb in CLL is poorly defined. Moreover, no data are currently available regarding treatment outcomes with other CD20 mAbs in CLL patients previously treated with rituximab or refractory to their last rituximab-containing regimen.Refractoriness to fludarabine or alemtuzumab was defined as failure to achieve at least partial remission to the last regimen or relapse within 6 months of treatment, including combinations. The prognosis for patients with fludarabine-refractory CLL was poor, with low response rates and short progression-free survival (PFS) and OS. 9,10 Outcomes were worse for patients also refractory to alemtuzumab, the CD52 mAb approved for fludarabine-refractory CLL. 9,10
Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukemia (CML) and are increasingly used in other malignancies. Despite the apparent selectivity of these agents significant side effects can occur mainly due to off target kinase inhibition. Clinical consequences of serosal inflammation, including pleural and pericardial effusions, have emerged as a frequent adverse event associated with dasatinib while occurring much less frequently during imatinib and nilotinib therapy. The pathogenesis is uncertain but may involve inhibition of platelet derived growth factor or expansion of cytotoxic T and natural killer cells. The development of serosal inflammation with dasatinib poses a significant challenge to physicians, as it cannot be predicted, the time of onset is variable, and management frequently requires repeat invasive procedures.
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