Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL).
We carried out a cohort study of 704 consecutive ...HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control.
For entire cohort, 5-year overall survival (OS) was 78% 95% confidence interval (CI): 74%–82% and 5-year progression-free survival (PFS) was 48% (95% CI: 44%–53%). In multivariate analysis, the use of AT during the patients’ life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%–73%). CR + PR rate was 85% with AT as second-line treatment.
AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.
Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI)≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based ...chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1year of adjuvant everolimus.
Patients with high-risk (IPI≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1year of everolimus 10mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety.
Between August 2009 and December 2013, 742 patients were randomized to everolimus (n=372) or placebo (n=370). Median follow-up was 50.4months (range 24.0–76.9). Overall, 47% of patients were≥65years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69–1.22; P=0.276). Two-year DFS rate was 77.8% (95% CI 72.7–82.1) with everolimus and 77.0% (95% CI 72.1–81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes.
Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained.
NCT00790036
The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy.
Thirty-two patients ...with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m2 i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles.
Median age was 63 years (range, 37–82 years). Median number of prior therapies was 2 (range, 1–4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% 95% confidence interval (CI) 29% to 67%, with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression.
Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.
PDF
