Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial

Clemens M Wendtner, Michael Hallek, Graeme A M Fraser, Anne-Sophie Michallet, Peter Hillmen, Jan Dürig, Matt Kalaycio, John G Gribben, Stephan Stilgenbauer, Andreas Buhler, Thomas J Kipps, Brendan Purse, Jennie Zhang, Sabine De Bedout, Jay Mei, Asher Chanan-Khan, Clemens M Wendtner, Michael Hallek, Graeme A M Fraser, Anne-Sophie Michallet, Peter Hillmen, Jan Dürig, Matt Kalaycio, John G Gribben, Stephan Stilgenbauer, Andreas Buhler, Thomas J Kipps, Brendan Purse, Jennie Zhang, Sabine De Bedout, Jay Mei, Asher Chanan-Khan

Abstract

The objective of this study was to evaluate the safety and efficacy of different lenalidomide starting doses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). CLL patients were randomized to receive lenalidomide at initial doses of 5, 10, or 15 mg/d (N = 103). Doses were escalated by 5 mg every 28-d up to a maximum of 25 mg/d; dose reductions in up to 5 mg decrements were permitted. The most common grade ≥3 adverse events (AEs) were neutropenia and thrombocytopenia. Ten patients died during therapy (four deaths considered as related to lenalidomide); 12 patients experienced second primary malignancies. The most common cause for treatment discontinuation was AEs. Overall response rates were similar across arms. Progression-free survival and overall survival rates were longer in patients who escalated treatment (to 15 or 20 mg/d) versus those who did not. Lower starting doses allowed subsequent dose escalation of lenalidomide while maintaining an acceptable tolerability profile in patients with relapsed/refractory CLL.

Keywords: CLL; Clinical trial; lenalidomide; phase II.

Conflict of interest statement

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1195497.

Figures

Figure 1.
Figure 1.
CONSORT patient flow diagram. CONSORT: Consolidated Standards of Reporting Trials; FC: fludarabine and cyclophosphamide.
Figure 2.
Figure 2.
Study treatment plan. Prednisolone 100 mg (or equivalent) was given prior to Infusions 1 and 2. If initial infusions were well tolerated, the glucocorticoid dose could be reduced to

Figure 3.

Median ofatumumab concentration–time plots.

Figure 3.

Median ofatumumab concentration–time plots.

Figure 3.
Median ofatumumab concentration–time plots.

Figure 4.

Median ofatumumab C max or…

Figure 4.

Median ofatumumab C max or C trough values at each cycle by best…

Figure 4.
Median ofatumumab Cmax or Ctrough values at each cycle by best response. Cmax: maximum observed concentration; Ctrough: minimum observed concentration prior to the next dose; CR: complete response; PR/nPR: partial response or nodal partial response; SD/PD/NE: stable disease, progressive disease, or not evaluable.
Figure 3.
Figure 3.
Median ofatumumab concentration–time plots.
Figure 4.
Figure 4.
Median ofatumumab Cmax or Ctrough values at each cycle by best response. Cmax: maximum observed concentration; Ctrough: minimum observed concentration prior to the next dose; CR: complete response; PR/nPR: partial response or nodal partial response; SD/PD/NE: stable disease, progressive disease, or not evaluable.

Source: PubMed

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