Pallawi Torka

Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.

Swallowing a bitter pill-oral arsenic trioxide for acute promyelocytic leukemia.

Parenteral arsenic trioxide (ATO) has been firmly established as a standard therapy for acute promyelocytic leukemia (APL). Despite widespread use of oral arsenicals in medicine historically, they had disappeared from modern pharmacopeia until oral ATO was redeveloped in Hong Kong in 2000. Since then, over 200 patients with leukemia (predominantly APL) have been treated with oral ATO in Hong Kong and China. Oral arsenic trioxide and other formulations of arsenic appear to have a clinical efficacy comparable to that of IV formulations. These drugs given orally also appear to have a slightly better safety profile, lower operational costs and improved convenience for patients. The clinical experience with oral ATO has previously been reported piecemeal as case series, pilot studies or subgroup analyses rather than in a comprehensive cohort. In this report we attempt to synthesize the published English language literature on oral arsenicals and present the argument for further development of these compounds. Systematic study of this drug with well-designed randomized multi-center clinical trials is needed to accelerate its development and incorporation into clinical practice.

T-Cell Lymphomas, Version 2.2018 Featured Updates to the NCCN Guidelines

Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkins lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

A Phase II Trial of Rituximab Combined With Pegfilgrastim in Patients With Indolent B-cell Non-Hodgkin Lymphoma

Background To explore the role of augmenting neutrophil function in B‐cell lymphoma, we conducted a phase II study evaluating the safety and clinical efficacy of pegfilgrastim and rituximab in low‐grade CD20+ B‐cell non‐Hodgkin lymphoma (B‐NHL). Patients and Methods Twenty patients with indolent B‐NHL were treated with rituximab (375 mg/m2) every other week for 4 doses, followed by every 2 months for 4 additional doses. Pegfilgrastim was administered subcutaneously 3 days before each dose of rituximab. Clinical activity and tolerability were assessed using standard criteria. Biologic monitoring included phenotype characteristics of the host neutrophils, changes in oxidative burst, and functional assays. Results The patient demographics included median age of 64 years, 70% were male, 70% had follicular lymphoma, and 90% had stage III‐IV disease. The median number of previous therapies was 2 (range, 0‐5); 90% had received previous anti‐CD20 monoclonal antibody therapy. The addition of pegfilgrastim to rituximab did not increase rituximab‐related toxicities. The overall response rate was 60% (12 of 20), with a complete response (CR) rate of 35% (7 of 20). The median progression‐free survival (PFS) duration was 17.9 months (95% confidence interval, 9.9‐27.6 months); the median overall survival was not reached. A shorter time‐to‐peak oxidative burst after the first dose of pegfilgrastim was associated with greater CR rates (P = .04) and longer PFS (P = .03). Conclusion The pegfilgrastim‐rituximab combination was well tolerated, with favorable outcomes compared with historical controls. A shorter time‐to‐peak oxidative burst was associated with higher CR rates and longer PFS. Our results support further evaluation of strategies that enhance the innate immune system to improve rituximab activity in B‐NHL. Micro‐Abstract The present phase II study has demonstrated that augmenting neutrophil function by the addition of pegfilgrastim can potentiate the clinical activity of rituximab in indolent B‐cell non‐Hodgkin lymphoma while retaining the excellent safety profile. Strategies to boost the innate immune system such as this combination warrant further study, especially in the frail, elderly population for whom therapeutic options are limited owing to poor tolerance.