Details

Autor(en) / Beteiligte

• Lampson, Benjamin L.
• Kim, Haesook T.
• Davids, Matthew S.
• Abramson, Jeremy S.
• Freedman, Arnold S.
• Jacobson, Caron A.
• Armand, Philippe A.
• Joyce, Robin M.
• Arnason, Jon E.
• Rassenti, Laura Z.
• Kipps, Thomas J.
• Fein, Joshua
• Fernandes, Stacey M.
• Hanna, John R.
• Fisher, David C.
• Brown, Jennifer R.

Titel

Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia

Ist Teil von

• Blood advances, 2019-04, Vol.3 (7), p.1167-1174

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• PI3 kinase (PI3K) activity is critical for survival of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL). Blockade of PI3K signaling with idelalisib is effective for the treatment of relapsed CLL in combination with the anti-CD20 antibody ofatumumab. In this single-arm, open-label, nonrandomized phase 2 study, we investigated the efficacy and safety of idelalisib with ofatumumab in 27 patients with treatment-naïve CLL in need of therapy. Patients were planned to receive idelalisib for 2 monthly cycles, then idelalisib and ofatumumab for 6 cycles, followed by idelalisib indefinitely. The study was closed early and all patients ceased therapy when an increased rate of death as a result of infection was observed on other first-line idelalisib trials. Median time on therapy was 8.1 months, and median duration of follow-up was 39.7 months. We previously reported high rates of hepatotoxicity in a smaller cohort of patients in this trial; toxicities necessitated therapy discontinuation in 15 patients after a median of 7.7 months. The most frequent grade ≥3 adverse events were transaminitis (52% of patients), neutropenia (33%), and colitis/diarrhea (15%). The best overall response rate (ORR) was 88.9%, including 1 complete response. Median progression-free survival (PFS) was 23 months (95% confidence interval [CI], 18-36 months); 11 patients have not yet required second-line therapy. Idelalisib and ofatumumab demonstrated an unacceptable safety profile in the first-line setting, which resulted in a short PFS despite a high ORR. Future development of PI3K inhibitors for use in treatment-naïve CLL will require novel approaches to mitigate toxicities. This trial was registered at www.clinicaltrials.gov as #NCT02135133. •Idelalisib plus ofatumumab have a high ORR but short PFS when used for treatment-naïve CLL.•The short PFS is likely a result of high rates of therapy discontinuation in the setting of transaminitis, colitis, and infections. [Display omitted]