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FILO real world results: ibrutinib was efficacious and demonstrated known safety profile in very elderly patients with relapsed/refractory Chronic Lymphocytic Leukemia

Mar 23, 2017

On 10th March 2017, Anne-Sophie Michallet, from the Centre Léon Bérard, CLCC, Lyon, France, and colleagues published real world results of 71 very elderly R/R CLL patients treated with ibrutinib in the American Journal of Hematology. The study was conducted by the French Innovative Leukemia Organization (FILO).

Between December 2013 and November 2014, 428 patients in France received ibrutinib, which had been granted temporary Authorization for Use (ATU) by the French National Agency for Medicines and Health Product Safety (ANSM). In the current study, the characteristics and outcomes of 71 patients aged over 75 are reported; data was collected from medical records and inputted into electronic case report forms by primary care physicians.

Key Highlights:

  • Median age = 79; 8–10 yrs older than pts in clinical trials of real-life practice cohorts to date
  • Median number of previous therapies = 3 (range, 1–9)
  • Heavily pre-treated and high-risk population: del(17p) = 26.2%; TP53 mutation = 19.4%
  • Started ibrutinib at 420mg/day = 70/71; at 280mg/day = 1/71
  • Within 1st treatment year, 37/71 pts (52.1%) experienced dose reduction (40.8%) or temporarily stopped ibrutinib (26.8%)
  • Median time to dose reduction = 8 weeks (range, 2–52)
  • The most frequent reasons for ibrutinib reduction/withdrawal = hematological toxicity (15.8%), arthralgia (13%), infection (10.5%), programmed surgery (8%), diarrhea (5.2%), bleeding (3%), and atrial fibrillation (2.6%)
  • Permanent ibrutinib discontinuation = 32.4% after a median exposure of 5 months (range, 1–16 months); main cause was bleeding symptoms, only 5.6% withdrawals due to PD
  • At last follow-up: pts alive on therapy = 63.4%; alive off therapy = 15.5%; died = 21.1% (various causes: 6/15 from CLL [including 3/6 Richter], 7/15 from infection, and 2/15 from heart disease)
  • At 6 and 12 months:
    • PR = 38.8% and 57.8%
    • PR + lymphocytosis = 46.9% and 35.6%
    • SD = 8.2% and 2.2%
    • PD = 6.1% and 4.4%
    • ORR = 85.7% and 93.4%
    • Infections = 21% and 10.5%
  • 12 month-PFS and OS = 77% and 91%; estimated median OS = 21 months
  • The only factor influencing PFS (HR = 4.430; P = 0.016) and DoR (HR = 4.931, P = 0.024) was arteritis/myocardial ischemia antecedents; this parameter had no impact on OS
  • Del(17p)/TP53 mutations were found to have a smaller impact on PFS and DoR than comorbidities had (HR = 0.827, P = 0.683; HR = 0.631; P = 0.543)

The authors concluded that their analysis of very elderly patients, the oldest cohort ever reported outside clinical trials, “supports the use of ibrutinib” in these patients. Treatment with ibrutinib was efficacious, but does require management of toxicities. However, decreasing the dose of ibrutinib did not negatively affect clinical outcomes, indicating dose reduction is a suitable strategy.

Expert Opinion

This is an observational study in 71 very old patients (many of them over 80 years) with highly pre-treated, relapsed or refractory CLL. All patients had ibrutinib as salvage treatment. Outcome data are favorable.

This report is of note as 80+ year old patients treated with ibrutinib were highly underrepresented in past ibrutinib trials as well as in the real-word ibrutinib cohorts published so far. In fact, this is the largest study cohort of that age group published in the context of ibrutinib treatment.

Results provide a rationale to not withhold ibrutinib salvage from patients with relapsed/refractory CLL just because of an age of 80+ years.

  1. Michallet A.S. et al. Ibrutinib in very elderly patients with relapsed/refractory chronic lymphocytic leukemia: A real-world experience of 71 patients treated in France A study from the French Innovative Leukemia Organization (FILO) group. Am J Hematol. 2017 Mar 10. DOI: 10.1002/ajh.24715. [Epub ahead of print].