Factors Affecting the Clinical Course of Follicular Lymphoma: A Multistate Survival Analysis Using Individual Patient Data from Eight Multicenter Randomized Clinical Trials.

Introduction/background: Leveraging the Follicular Lymphoma Analysis of Surrogacy Hypothesis database of individual patient data from first-line clinical trials, we studied the clinical course of follicular lymphoma (FL) and investigated clinical factors associated with FL outcomes.

Patients And Methods: We examined 2428 patients from 8 randomized trials using multistate survival models with 4 states: induction treatment, progression, death from FL, and death from other causes. We utilized Aalen-Johansen estimator and Cox models to assess the likelihood of FL outcomes and quantify predictors' effects.

Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial.

The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule.

Prognostic value of POD24 validation in follicular lymphoma patients initially treated with chemotherapy-free regimens in a pooled analysis of three randomized trials of the Swiss Group for Clinical Cancer Research (SAKK).

The relapse of follicular lymphoma (FL) within 24 months (POD24) of chemoimmunotherapy has been associated with poor survival. We analyzed a pooled dataset of three randomized trials including FL patients with advanced disease, conducted by the Swiss Group for Clinical Cancer Research (SAKK). Overall, POD24 was observed in 27% of 318 patients, but rate variance among studies suggested that the rituximab schedule might affect POD24 rate.

Controversies in the Treatment of Follicular Lymphoma.

The overall prognosis of patients with follicular lymphoma has substantially improved over the last decades with a 10-year overall survival of around 80% for the majority of patients. However, for most patients follicular lymphoma it is still a relapsing and remitting disease. Furthermore, certain subsets of patients still have much shorter survival.

International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia.

Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]).

Risk factors for renal toxicity after inpatient cisplatin administration.

Background: After several decades, cisplatin continues to be an essential drug for the treatment of several tumors, however, its potential nephrotoxicity is still a clinically relevant issue. Identification of predisposing factors for renal toxicity could be of value to warrant prophylactic measures.

Methods: We analyzed data from 198 patients with various tumor types, treated with cisplatin containing regimens in our regional cancer center in a two-years period.

Diagnostic Performance of F-FDG PET or PET/CT for Detection of Post-Transplant Lymphoproliferative Disorder: A Systematic Review and a Bivariate Meta-Analysis.

Background: Some studies evaluated the diagnostic performance of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) for the detection of post-transplant lymphoproliferative disorder (PTLD). As there is no clear consensus about the diagnostic accuracy of these imaging methods, we performed a meta-analysis on this topic.

Methods: A comprehensive computer literature search of PubMed, Embase, and Cochrane library databases through December 2019 was performed.

Primary Cutaneous Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma.

Large B-cell lymphomas include several subtypes. Recently, anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma has been delineated as a distinct entity involving mostly lymph nodes and rarely affecting extranodal sites. We describe the first case of a primary cutaneous ALK-positive large B-cell lymphoma in a 48-year-old man with a solitary nodule on the back, and describe the histologic and phenotypic features.

Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy.

The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months.

Melphalan dose in myeloma patients ≥65 years of age undergoing high-dose therapy and autologous stem cell transplantation: a multicentric observational registry study.

The optimal melphalan dose prior to autologous stem cell transplantation (ASCT) is not known for elderly multiple myeloma (MM) patients. We analyzed data of all MM patients ≥65 years (n = 388) enrolled in the observational Swiss Blood Stem Cell Transplantation Registry. The median age was 67 years (65-77).

Maintenance Treatment for Patients With Mantle Cell Lymphoma: A Systematic Review and Meta-analysis of Randomized Trials.

Current treatment of patient with mantle cell lymphoma (MCL) is insufficient and does not result in cure. To assess the efficacy and safety of maintenance therapy for patients with MCL, we performed a systematic review and meta-analysis of randomized controlled trials. Six trials randomizing 858 patients were included in the meta-analysis.

Choosing wisely in oncology: necessity and obstacles.

In the last decades, the survival of many patients with cancer improved thanks to modern diagnostic methods and progresses in therapy. Still for several tumours, especially when diagnosed at an advanced stage, the benefits of treatment in terms of increased survival or quality of life are at best modest when not marginal, and should be weighed against the potential discomfort caused by medical procedures. As in other specialties, in oncology as well the dialogue between doctor and patient should be encouraged about the potential overuse of diagnostic procedures or treatments.

Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial.

Objective: Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial.

Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

Background: The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed.

Patients And Methods: Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed.

Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma.

The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy.

Rituximab: a benchmark in the development of chemotherapy-free treatment strategies for follicular lymphomas.

Background: With the introduction of the anti-CD20 antibody rituximab, the outcome of patients with follicular lymphoma (FL) has greatly improved over the last two decades. First-line prolonged rituximab monotherapy is effective, achieving long-term remission and prolonged failure-free survival in some patients. Additionally, rituximab has been shown to synergize with chemotherapeutic and novel targeted agents alike with measurable gains in duration of response.

Pros and cons of rituximab maintenance in follicular lymphoma.

Follicular lymphoma (FL) is the most prevalent indolent non-Hodgkin lymphoma. Most patients present with advanced disease and are incurable with current therapy. The approval of rituximab has revolutionized the treatment of follicular lymphoma when administered in the induction setting for high-tumor burden disease, but the use of rituximab as a maintenance therapy (MR) continues to be a point of controversy.

Multicenter Phase II Study of Panitumumab in Platinum Pretreated, Advanced Head and Neck Squamous Cell Cancer.

Lessons Learned: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies.

Rituximab maintenance improves overall survival of patients with follicular lymphoma-Individual patient data meta-analysis.

Background: Randomised trials of rituximab maintenance (MR) for patients with follicular lymphoma support improved progression-free survival (PFS), but the effect on overall survival has been inconclusive. To evaluate the effect of MR on overall survival according to patient and disease characteristics, and to explore certain adverse events, we performed an individual patient data (IPD) meta-analysis.

Methods: All investigators of randomised controlled trials that compared MR therapy with observation or treatment only at relapse (no MR) for patients with follicular lymphoma were invited to participate in an IPD meta-analysis.

Rituximab: 13 open questions after 20years of clinical use.

Rituximab improved the prognosis of all B-cell derived lymphoproliferative diseases, but despite 20years of intensive use, it remains a drug with a number of still obscure characteristics and unanswered questions. These include the mechanism of action and of resistance, the optimal schedule, the interaction with chemotherapy, as well as predictive factors for response rate and duration. Despite being very well tolerated, the question of its long term side effects and the risks of the administration near to a pregnancy have only recently been addressed.

Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual Patient-Level Analysis of Multiple Randomized Trials.

Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed.