Low‐dose fludarabine and cyclophosphamide combined with rituximab in the first‐line treatment of elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): long‐term results of project Q‐lite by the Czech CLL Study Group

Abstract

Therapeutic options used to be very limited for treatment-na€ ıve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo-immunotherapy. Because dose-reduced fludarabine-based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low-dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full-dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy-chain variable-region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m 2 intravenously (iv) or 20 mg/m 2 orally on days 1-3 and cyclophosphamide to 150 mg/m 2 iv/orally on days 1-3. Grade 3-4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression-free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low-dose FCR is a well-tolerated and effective first-line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726).

FIRE Study: Real-World Effectiveness and Safety of Ibrutinib in Clinical Practice in Patients with CLL and MCL

“…In the observational informCLL registry of patients who received treatment for CLL/SLL, IGHV mutation status testing was performed in only 12% of patients; 71% of these had an unmutated gene, of which 39% received chemoimmunotherapy [25]. In addition, a Czech prospective observational study assessing safety and efficacy of low-dose FCR in elderly/comorbid patients showed that, while there was no difference in response between patients with mutated or unmutated IGHV, PFS was markedly longer in patients with mutated IGHV [26]. Testing for IGHV is advised in the recommendations of the French CLL Study Group and International Workshop on Chronic Lymphocytic Leukemia guidelines prior to first-line therapy [20,27], which should help provide patients with optimal therapy moving forward.…”

The CLL comorbidity index in a population-based cohort: a tool for clinical care and research

“…The underlying cause remains to be investigated; however, adverse prognostic biomarkers were more common in the CLL-CI high-risk group, suggesting the possibility of underlying mechanistic associations between comorbidities and aggressiveness of CLL. 16 This could be due to underlying factors that influence both CLL biology and the development of comorbidities or the possibility that aggressive CLL causes comorbidities. Our working hypothesis is that the biological link among the CLL-CI, high-risk biomarkers, and shorter survival is chronic inflammation and immune dysfunction caused by metabolic syndrome, vascular disease, and dysbiosis.…”

Chemoimmunotherapy in the First-Line Treatment of Chronic Lymphocytic Leukaemia: Dead Yet, or Alive and Kicking?

“…While the incidence of severe neutropenia was similar (43 vs. 37%), more infections (19 vs. 8%) were recorded in the BR arm [53]. Finally, FCR with attenuated doses of chemotherapy was reported in smaller studies [54,55].…”