Risk-adapted, ofatumumab-based chemoimmunotherapy and consolidation in treatment-naïve chronic lymphocytic leukemia: a phase 2 study

Sanjal Desai, Clifton Mo, Erika M. Gaglione, Constance M. Yuan, Maryalice Stetler-Stevenson, Xin Tian, Irina Maric, Laura Wake, Mohammed Z. Farooqui, Dennis C. Drinkwater, Susan Soto, Janet Valdez, Thomas E. Hughes, Pia Nierman, Jennifer Lotter, Gerald E. Marti, Christopher Pleyer, Clare Sun, Jeanine Superata, Cydney NicholsSarah E.M. Herman, Margaret A. Lindorfer, Ronald P. Taylor, Adrian Wiestner, Inhye E. Ahn

Research output: Contribution to journalArticlepeer-review

Abstract

High-risk cytogenetics and minimal residual disease (MRD) after chemoimmunotherapy (CIT) predict unfavorable outcome in chronic lymphocytic leukemia (CLL). This phase 2 study investigated risk-adapted CIT in treatment-naïve CLL (NCT01145209). Patients with high-risk cytogenetics received induction with fludarabine, cyclophosphamide, and ofatumumab. Those without high-risk cytogenetics received fludarabine and ofatumumab. After induction, MRD positive (MRD+) patients received 4 doses of ofatumumab consolidation. MRD negative (MRD-) patients had no intervention. Of 28 evaluable for response, all responded to induction and 10 (36%) achieved MRD-. Two-year progression-free survival (PFS) was 71.4% (CI95, 56.5–90.3%). There was no significant difference in median PFS between the high-risk and the standard-risk groups. Ofatumumab consolidation didn’t convert MRD + to MRD-. In the MRD + group, we saw selective loss of CD20 antigens during therapy. In conclusion, risk-adapted CIT is feasible in treatment-naïve CLL. Ofatumumab consolidation didn’t improve depth of response in MRD + patients. Loss of targetable CD20 likely reduces efficacy of consolidation therapy.

Original languageEnglish (US)
Pages (from-to)1816-1827
Number of pages12
JournalLeukemia and Lymphoma
Volume62
Issue number8
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • Chronic lymphocytic leukemia
  • chemoimmunotherapy
  • minimal residual disease
  • ofatumumab
  • trogocytosis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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