In the journal Leukemia in January 2017, Asher Chanan-Khan, from the Mayo Clinic, Jacksonville, Florida, and colleagues reported the results of the ORIGIN phase III randomized, open-label, multicenter trial (NCT00910910) comparing lenalidomide (LEN) or chlorambucil (CHB) in the first-line treatment of CLL in older patients.
The study recruited 450 patients between November 2009 and March 2013. The trial ended early as the data monitoring committee noticed increased deaths in only one of the treatment arms (LEN), resulting in an imbalance. Patients aged 81 or older discontinued the study in April 2013. By July 2013, all LEN patients had discontinued treatment, and by March 2014 all CHB patients had discontinued treatment.
- LEN: Creatinine Clearance (CrCl) ≥30 and <60 ml/min given 2.5mg per day increased to 7.5mg if tolerated, CrCl ≥60 ml/min given 5mg per day increased to 15mg if tolerated
- CHB: 0.8mg/kg on D1 and D15 of each 28-day cycle, max 13 cycles
- Treatment continued until intolerable toxicity or progressive disease
- Balanced baseline characteristics across treatment groups
- Median follow-up 11.8 months
- Median PFS: LEN = 30.8 months, CHB = 23.0 months (P=0.323)
- Death or PD in favor of CHB - HR 1.21 (90% CI, 0.88–1.66)
- Deaths at April 2013 cut-off: LEN = 36 (16.0%), CHB 25 (11.1%)
- More deaths seen in older patients
- ORR at April 2013 cut-off: LEN = 55.1%, CHB = 65.8% (P=0.026)
- CR: LEN = 2.7%, CHB = 9.8%
- Duration of response in favor of LEN - HR 0.74 (90% CI, 0.47–1.16; P=0.262)
- Treatment-Emergent Adverse Events (TEAE)
- TEAE drug interruptions/reductions: LEN = 63.8% pts, CHB = 21.1% pts
- TEAE total: LEN = 95.1% pts, CHB = 90.1% pts
- Serious TEAE: LEN = 63.8% pts, CHB = 38.6% pts
The authors concluded that lenalidomide did not result in longer PFS than chlorambucil, but was associated with higher incidence of TEAEs, serious TEAEs, and deaths than chlorambucil. Therefore, the authors stated that lenalidomide should not be used as a monotherapy in first-line treatment of CLL, especially not in older patients.
- Chanan-Khan A. et al. Randomized phase 3 study of lenalidomide versus chlorambucil as first-line therapy for older patients with chronic lymphocytic leukemia (the ORIGIN trial). Leukemia. 2017 Jan 31. DsOI: 1038/leu.2017.47. [Epub ahead of print: 2017 Jan 31]