A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia

Ian W. Flinn, Amy S. Ruppert, William Harwin, David Waterhouse, Steven Papish, Jeffrey A. Jones, John Hainsworth, John C. Byrd

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Abstract

Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI-WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression-free survival (PFS) of ofatumumab as front-line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89% (1996 NCI-WG criteria), respectively (54 and 68%, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24-month estimated PFS rates were 46 and 78%, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high-risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well-tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020–1025, 2016.

Original languageEnglish (US)
Pages (from-to)1020-1025
Number of pages6
JournalAmerican Journal of Hematology
Volume91
Issue number10
DOIs
StatePublished - Oct 1 2016

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B-Cell Chronic Lymphocytic Leukemia
Disease-Free Survival
Therapeutics
ofatumumab
Cytogenetics
Survival Rate
Maintenance
Safety
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Flinn, Ian W. ; Ruppert, Amy S. ; Harwin, William ; Waterhouse, David ; Papish, Steven ; Jones, Jeffrey A. ; Hainsworth, John ; Byrd, John C. / A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia. In: American Journal of Hematology. 2016 ; Vol. 91, No. 10. pp. 1020-1025.
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abstract = "Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58{\%} response rate (1996 NCI-WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression-free survival (PFS) of ofatumumab as front-line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89{\%} (1996 NCI-WG criteria), respectively (54 and 68{\%}, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24-month estimated PFS rates were 46 and 78{\%}, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high-risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well-tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020–1025, 2016.",
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A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia. / Flinn, Ian W.; Ruppert, Amy S.; Harwin, William; Waterhouse, David; Papish, Steven; Jones, Jeffrey A.; Hainsworth, John; Byrd, John C.

In: American Journal of Hematology, Vol. 91, No. 10, 01.10.2016, p. 1020-1025.

Research output: Contribution to journalArticle

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