A network meta-analysis of progression free survival and overall survival in first-line treatment of chronic lymphocytic leukemia.

BACKGROUND: A limited evidence exists regarding comparisons of clinical effectiveness of available therapies for first-line treatment of chronic lymphocytic leukemia (CLL). METHODS: We compared available therapies for treatment-naïve, symptomatic CLL regarding progression free survival (PFS) and overall survival (OS) in all the identified random control trials and in subgroups composed of younger/fit and older/unfit patients, using a Bayesian network meta-analysis. RESULTS: In younger/fit patients we obtained median of projected mean PFS of: 19, 26, 31, 43, 51 and 75months for chlorambucil, fludarabine, alemtuzumab, fludarabine with cyclophosphamide (FC), bendamustine and fludarabine with cyclophosphamide and rituximab (FCR), respectively. We noted median OS of: 59, 66, 66, 70months for FC, chlorambucil, FCR and fludarabine, respectively. In older/unfit patients we noted PFS of: 16, 17, 24, 30, 60months for chlorambucil, fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and 90months for fludarabine, RClb, chlorambucil and GClb, respectively. CONCLUSIONS: Our results suggest that: (1) FCR has higher potential of preventing CLL progression in younger/fit patients over four therapy options, which were subject of previous meta-analysis but also over bendamustine; (2) in these patients FCR does not entail prolonging of OS in comparison with chlorambucil and it is outperformed by fludarabine; (3) in older/unfit patients GClb demonstrates longer projected PFS than all assessed comparators; (4) in this group GClb has also the highest potential of increasing OS.

Bendamustine-rituximab: a cost-utility analysis in first-line treatment of indolent non-Hodgkin's lymphoma in England and Wales.

OBJECTIVE: To evaluate the cost-effectiveness of bendamustine-rituximab (B-R) compared with CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and CVP-R (cyclophosphamide, vincristine, prednisone, rituximab) as first-line treatment for patients with advanced indolent non-Hodgkin's lymphoma (NHL). METHODS: A patient-level simulation was adapted from the model used by the University of Sheffield School of Health and Related Research (ScHARR) in a health technology appraisal of rituximab for first-line treatment of follicular lymphoma. This approach allowed modelling of the complex treatment pathways in indolent NHL. Data from a Phase 3 randomized, open-label trial were used to compare B-R with CHOP-R. The relative efficacy of CHOP-R and CVP-R was estimated using an indirect treatment comparison similar to the original ScHARR approach. The analysis was conducted from the perspective of the National Health Service in England and Wales, using a lifetime time horizon. A number of one-way sensitivity and scenario analyses were conducted, including one using recently published data comparing CVP-R with CHOP-R. RESULTS: The deterministic incremental cost-effectiveness ratio (ICER) was £5249 per quality adjusted life year (QALY) for B-R vs CHOP-R, and £8092 per QALY for B-R vs CVP-R. The alternative scenario using direct data comparing CVP-R with CHOP-R approximately halved the ICER for B-R vs CVP-R to £4733. Owing to its better toxicity profile, B-R reduced the cost of treating adverse events by over £1000 per patient vs CHOP-R. LIMITATIONS: The main limitations were: immaturity of overall survival data from the Phase 3 trial; reliance on quality-of-life data from previous health technology appraisals (as this was not collected in the trial); and a lack of direct evidence or a network of connected evidence comparing B-R with CVP-R. CONCLUSIONS: The ICERs for B-R vs CHOP-R and CVP-R were considerably below the thresholds normally regarded as cost-effective in England and Wales (£20,000-30,000 per QALY).

Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin's lymphoma patients : A multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL).

Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody. One hundred seventy-five relapsed or refractory lymphoma patients were enrolled. The median age was 69 years (range 26-87). Seventy-nine patients were relapsed, 35 were refractory and 61 presented a progressive disease after partial response. The diagnoses were 60 indolent non-follicular lymphomas, 34 diffuse large B-cell lymphomas, 48 follicular lymphomas, 30 mantle cell lymphomas and three peripheral T-cell lymphomas. All patients were evaluable for response: 52 (29%) with complete remission, 72 (43%) with partial response with an overall response rate of 71%, and 51 non-responders. With a median observation period of 10 months (1-43), 70% of patients are alive. In summary, this retrospective study shows that treatment with bendamustine alone or in combination with rituximab is a safe and effective regimen in a subset of multi-resistant patients.