Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy

Roxanne C Jewell, Thomas J Kipps, Jan Dürig, Laimonas Griskevicius, Stephan Stilgenbauer, Lukáš Smolej, Jiří Mayer, Georg Hess, Francisco J Hernandez-Ilizaliturri, Swaminathan Padmanabhan-Iyer, Lei Fang, Nancy Goldstein, Michele Gorczyca, Ira Gupta, Steen Lisby, William G Wierda, Hx-CD20-407 Study Investigators, Roxanne C Jewell, Thomas J Kipps, Jan Dürig, Laimonas Griskevicius, Stephan Stilgenbauer, Lukáš Smolej, Jiří Mayer, Georg Hess, Francisco J Hernandez-Ilizaliturri, Swaminathan Padmanabhan-Iyer, Lei Fang, Nancy Goldstein, Michele Gorczyca, Ira Gupta, Steen Lisby, William G Wierda, Hx-CD20-407 Study Investigators

Abstract

Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median Cmax and Ctrough values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher Cmax and Ctrough values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics.

Trial registration: www.clinicaltrials.gov (NCT00410163).

Keywords: Chemoimmunotherapy; chronic lymphocytic leukemia; ofatumumab; pharmacokinetics.

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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