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

- We compared progression free and overall survivals in first-line therapies of CLL.
- We used Bayesian network meta-analysis to model hazard with fractional polynomials.
- FCR has the highest potential of prolonging PFS in younger/fit patients.
- Fludarabine insures the longest median OS in younger/fit patients.
- Obinutuzumab with chlorambucil is the best choice for older/unfit patients.

BackgroundA limited evidence exists regarding comparisons of clinical effectiveness of available therapies for first-line treatment of chronic lymphocytic leukemia (CLL).MethodsWe 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.ResultsIn younger/fit patients we obtained median of projected mean PFS of: 19, 26, 31, 43, 51 and 75 months 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, 70 months for FC, chlorambucil, FCR and fludarabine, respectively. In older/unfit patients we noted PFS of: 16, 17, 24, 30, 60 months for chlorambucil, fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and 90 months for fludarabine, RClb, chlorambucil and GClb, respectively.ConclusionsOur 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.