Ofatumumab Consolidation Regimen Might Lengthen CLL Treatment-Free Survival

Treatment-naive chronic lymphocytic leukaemia patients given ofatumumab-based chemotherapy may benefit from further consolidation treatment with the agent

medwireNews: Ofatumumab -based consolidation after front-line induction chemotherapy with the anti-CD20 antibody may extend treatment-free survival (TFS) in patients with chronic lymphocytic leukaemia (CLL), researchers suggest.

The team reports results from the second arm of a phase II trial testing ofatumumab alongside pentostatin and cyclophosphamide , in 34 patients, 91% of whom completed all six cycles of induction treatment.

These individuals began ofatumumab-based consolidation within 2 months of completing induction therapy, with 84% of the patients receiving all six cycles of ofatumumab given at a dose of 1000 mg every 4 weeks.

The primary endpoint of TFS at 18 months of follow-up was achieved by 94.1% of the patients, write Tait Shanafelt, from the Mayo Clinic in Rochester, Minnesota, USA, and co-authors in The Lancet Haematology.

This compared with an 18-month TFS rate of 87.5% for patients in the first arm of the phase II trial who had received only the ofatumumab-based induction regimen, they say.

And in a landmark analysis including only patients who completed induction therapy, median TFS was estimated to be 52.4 months in the 48 patients given only induction therapy versus unreached in the second arm who also received the consolidation treatment.

Eight patients given the consolidation regimen experienced grade 3 or more severe neutropenia, of whom six had grade 4 events. A further two patients experienced grade 3 or worse infection, with individuals also reporting allergy, pneumonitis, anaemia, fatigue, neurological, metabolic and vascular grade 3 side effects.

Haematological toxicity, driven by neutropenia, was also the main cause of the significantly higher rate of grade 3 or more severe adverse events in the patients given consolidation treatment than those given only the induction regimen, at 68% versus 27%.

“The benefits of consolidation and maintenance with single-agent ofatumumab in the frontline setting might be greater than those in the relapsed setting”, the researchers postulate.

“In particular, use of single-agent ofatumumab prolongs treatment-free survival and might translate into improved overall survival.”

Julio Delgado and Emili Montserrat, from the University of Barcelona in Spain, write in an associated comment that the findings, taken alongside earlier studies, indicate that maintenance therapy might prolong progression-free survival, if perhaps not overall survival, in CLL.

But they emphasize the need to determine the optimal dosing and scheduling for anti-CD20 antibody treatment, how to select patients for maintenance therapy, the impact of maintenance on response to any subsequent therapy, and the burden of toxicity.

“Looking to the future, the potential advantages of maintenance therapy with anti-CD20 monoclonal antibodies or kinase inhibitors over watchful waiting needs to be further assessed in randomised clinical trials designed to address the issues just outlined here”, they conclude. 


Strati P, Lanasa M, Call TG, et al. Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial. Lancet Haematol 2016; Advance online publication 1 August. DOI: http://dx.doi.org/10.1016/S2352-3026(16)30064-3

Delgado J, Montserrat E. Maintenance therapy in chronic lymphocytic leukaemia. Lancet Haematol 2016; Advance online publication 1 August. DOI: http://dx.doi.org/10.1016/S2352-3026(16)30081-3

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