A Genetic Risk-Stratified Phase 2 Study of Fludarabine/Antibody Combinations in Symptomatic, Untreated CLL: Results from Cancer and Leukemia Group B (CALGB) 10404 (Alliance)

Conference Correspondent - ASCO 2017 - Chronic Lymphocytic Leukemia, Conference Correspondent

In this randomized phase 2 study, researchers seek to define the optimal foundational chemoimmunotherapy regimen in patients with non-del(11q) disease and to ascertain the role of lenalidomide (L) in symptomatic, untreated CLL.

Patients with untreated CLL requiring therapy were randomized to the following treatment arms: fludarabine plus rituximab (FR) for 6 cycles (all cycles were 28 days), including only non-del(11q) patients; FR for 6 cycles followed by L at 5 mg on days 1 to 21 of the first cycle, then 10 mg on days 1 to 21 of the next 5 cycles, including only non-del(11q) patients; FR plus cyclophosphamide (FCR) for 6 cycles, including patients with and without del(11q); and FCR for 6 cycles followed by L at 5 mg on days 1 to 21 of the first cycle, then 10 mg on days 1 to 21 of the next 5 cycles, including only del(11q) patients.

Patients with del(11q22.3) in at least 20% of cells were excluded from the primary analysis, so that only those patients without del(11q) were evaluated to determine whether the 2-year progression-free survival (PFS) rate improved.

A total of 342 non-del(11q) patients with CLL were randomized to treatment with FR (n = 123), FR+L (n = 109), or FCR (n = 110). Baseline characteristics were similar across arms. At 2 years, 64% of patients in the FR arm achieved PFS, compared with 71% in the FR+L arm and 74% in the FCR arm. Median PFS was 43 months, 66 months, and 78 months for FR, FR+L, and FCR, respectively, and the difference between FR versus FR+L (P = 0.03) and FR versus FCR (P <0.01) was statistically significant. Median overall survival (OS) has not been reached for any arm. OS at 1, 2, and 3 years was similar across the 3 arms, although there was a plateau in OS, with no events beyond 41 months, in the FR+L arm, as opposed to FR/FCR, in which events continued to occur. The most common adverse events were cytopenias and infections.

The researchers concluded that both FR+L and FCR met the primary end point. Moreover, FR+L extended PFS relative to FR, and a plateau in survival differentiated this arm from the FR/FCR arms. As demonstrated by these results, L appears to increase long-term survival and warrants further studies comparing FR+L with FCR, or studies incorporating L into other novel treatment regimens.

Ruppert AS, et al. ASCO Abstract 7503.

Related Items
Omadacycline for Acute Bacterial Skin and Skin Structure Infections: Integrated Analysis of Randomized Clinical Trials
December 2018 Vol 11, No 9 published on December 27, 2018 in Conference Correspondent
Improved Quality of Life in Adults with Acute Bacterial Skin and Skin Structure Infections with Omadacycline or Linezolid Therapy
December 2018 Vol 11, No 9 published on December 27, 2018 in Conference Correspondent
Omadacycline In Vitro Activity Against a Molecularly Characterized Collection of Clinical Isolates with Known Tetracycline Resistance Mechanisms
December 2018 Vol 11, No 9 published on December 27, 2018 in Conference Correspondent
Integrated Safety Summary of Omadacycline, A Novel Aminomethylcycline Antibiotic
December 2018 Vol 11, No 9 published on December 27, 2018 in Conference Correspondent
Sustained Response Following Discontinuation of MTX in Subcutaneous Tocilizumab-Treated Patients with RA
Conference Correspondent published on November 9, 2017 in ACR 2017, Conference Correspondent
Last modified: June 6, 2017
  •  Association for Value-Based Cancer Care
  • Oncology Practice Management
  • Value-Based Cancer Care
  • Value-Based Care in Rheumatology
  • Rheumatology Practice Management
  • Urology Practice Management
  • Lynx CME