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We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus ≤6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183-0.286]; p

The National Cancer Research Network (NCRN) is currently coordinating a Phase III randomised study (LY05) comparing fludarabine and cyclophosphamide (FC) with or without rituximab (R) for previously untreated mantle cell lymphoma (MCL). The combination of FC is well-recognised as significantly immunosuppressive and there are concerns that adding rituximab may increase infection risk further. The impact of rituximab on other markers of toxicity is also unclear. We analysed the toxicity data on 139 patients treated within the NCRN LY05 trial. Non-hematological toxicity was similar between the two treatment arms. The only difference in hematological toxicity was a higher rate of lymphocytopenia with fludarabine cyclophosphamide and rituximab (FCR), which did not translate into increased febrile episodes or infections. In conclusion, the addition of rituximab to FC for previously untreated MCL has no significant impact on toxicity.

Mantle cell lymphoma (MCL) is an uncommon B-cell neoplasm with male predominance and a median age at presentation in the mid-60s. The majority of patients follow an aggressive clinical course with ...

In the March edition of the journal, Kouroukis et al. [1] describe a phase II study of the combination of bortezomib (Velcade) with gemcitabine in relapsed mantle cell lymphoma (MCL). The study was primarily designed to determine the efficacy of this combination in patients having received up to three prior lines of therapy. Both bortezomib and gemcitabine have demonstrable single-agent activity in this disease [2,3], and the authors adopted a dosing regimen that had previously been established in a solid tumor phase I study [4]. This involved bortezomib given at 1.0 mg/m IV on days 1, 4, 8, and 11 with gemcitabine at 1000 mg/m IV on days 1 and 8 of a 21-day schedule. In total, 26 patients were eligible for assessment. The observed overall response rate was 60% (15 patients) with an additional nine patients having stable disease, which meant that only one patient had initial progression. The median progression-free survival was 11.4 months. The major toxicity observed was hematological with virtually all patients experiencing some cytopenia, and in almost half of the patients this was severe (grade III/IV). Significant neurological toxicity occurred in only two (8%) patients, although ‘pain’ was seen in an additional four (15%). In common with many bortezomib studies fatigue was a common nonhematological side effect, with 11% experiencing grade III/IV toxicity. As a consequence of the hematological toxicity just over 50% of cycles were given at the intended dose intensity, and in patients who had previously received high-dose therapy this fell to 25%. This is a relatively small study that has combined two drugs with proven single-agent activity in MCL. The combination is clearly active with most patients achieving some degree of disease response, but how does this compare to other published regimens? Bortezomib as a single agent produces response rates of up to 46% [5–8] in small phase II settings, and 33% when evaluated in a multicenter international registration study [3]. In all of these studies the patient populations examined were more heavily pretreated than in the current study. In the study of Kouroukis et al. 58% of the patients had low-risk disease according to the Mantle Cell Lymphoma International Prognostic Index (MIPI), and 73% had received only one prior chemotherapy regimen. This is therefore a relatively lightly treated population who you might expect to have a good response to secondline chemotherapy. A suitable comparison would be two multicenter studies evaluating fludarabine combinations with rituximab [9,10], where the majority of patients were at first relapse. In both of these studies the observed response rates were over 70%, and were maintained for approximately 1 year. The observed response rate in the study from Kouroukis et al. would probably be higher if rituximab had been added to their combination, and so all these results are probably broadly similar. The stated attraction of this regimen is that it is a non-anthracycline containing combination. However, the hematological toxicity described would appear to limit its applicability to those patient groups where you might wish to avoid this class of drug, namely more elderly patients with limited bone marrow reserve. In addition, this would also appear to limit its use in patients following high-dose procedures. The hematological toxicity would also

Mantle cell lymphoma (MCL) remains an incurable hematological malignancy with a median overall survival (OS) of 3–5 years. The clinical course can be extremely variable with some individuals demons...

Mycosis fungoides (MF) is an indolent cutaneous T cell tumour that accounts for almost 50% of all primary cutaneous lymphomas. It typically arises in older adults with a median age at diagnosis of ...

Tumor lysis syndrome (TLS) is characterised by a combination of metabolic disturbances resulting from the rapid release of neoplastic intracellular contents [1]. It is an oncological emergency occu...

The Bruton's tyrosine kinase (BTK) inhibitors have been reported to deliver high response rates without significant toxicity in relapsed mantle cell lymphoma (MCL). The lead compound, ibrutinib, ha...

Rituximab is a chimeric anti-CD20 monoclonal antibody that is used widely in the management of lymphoproliferative disorders. Currently, rituximab is indicated in a variety of B-cell non-Hodgkin lymphomas (NHLs), chronic lymphocytic leukemia (CLL) and rheumatoid arthritis, and is increasingly being used across a range of other conditions [1 – 3]. Th e administration of rituximab is associated with infusion-related toxicities, ranging from fever, rash, hypotension and tachycardia to severe reactions such as respiratory distress and fatal cytokine release syndrome. Th e incidence of infusion reactions is highest during the fi rst infusion, but decreases signifi cantly with subsequent infusions [4,5]. Minor infusion reactions occur in approximately 50% of patients during their fi rst dose and usually within 1 – 2 h from commencing the infusion; these are severe in around 7% of patients [6]. Th e summary of product characteristics (SPC) for rituximab requires prolonged infusion times given under close supervision by an experienced physician and in an environment where full resuscitation facilities are available [7]. Its use outside of such an environment has not been described. Rituximab use has increased signifi cantly as the indications for its use have expanded. Th is has had a major impact on resource utilization within hematology and oncology day-units leading to signifi cant capacity issues. Derriford Hospital in Plymouth serves a large geographical area with patients having to travel long distances to attend the hospital. In 2009 we published the results of a randomized trial that explored the delivery of chemotherapy in local community clinics as well as the tertiary cancer center [8]. Patients received their treatment in both settings and then elected to complete therapy in the facility of their choice. Th e community setting was shown to improve the overall patient experience in terms of convenience and accessibility, and all patients except one elected to complete their therapy in these units. Following this successful study, patients have moved to these local facilities as appropriate, with trained chemotherapy nurses from within the hematology and oncology day units administering the chemotherapy. Following many