Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial

Abstract

Key Points• Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL.• Updated results on safety and efficacy of the CLL8 trial.Despite promising results with targeted drugs, chemoimmunotherapy with fludarabine, cyclophosphamide (FC), and rituximab (R) remains the standard therapy for fit patients with untreated chronic lymphocytic leukemia (CLL). Herein, we present the long-term follow-up of the randomized CLL8 trial reporting safety and efficacy of FC and FCR treatment of 817 treatment-naïve patients with CLL. The primary end point was progressionfree survival (PFS). With a median follow-up of 5.9 years, median PFS were 56.8 and 32.9 months for the FCR and FC group (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.50-0.69, P < .001). Median overall survival (OS) was not reached for the FCR group and was 86.0 months for the FC group (HR, 0.68; 95% CI, 0.54-0.89, P 5 .001). In patients with mutated IGHV (IGHV MUT), FCR improved PFS and OS compared with FC (PFS: HR, 0.47; 95% CI, 0.33-0.68, P < .001; OS: HR, 0.62; 95% CI, 0.34-1.11, P 5 .1). This improvement remained applicable for all cytogenetic subgroups other than del(17p). Long-term safety analyses showed that FCR had a higher rate of prolonged neutropenia during the first year after treatment (16.6% vs 8.8%; P 5 .007). Secondary malignancies including Richter's transformation occurred in 13.1% in the FCR group and in 17.4% in the FC group (P 5 .1). First-line chemoimmunotherapy with FCR induces long-term remissions and highly relevant improvement in OS in specific genetic subgroups of fit patients with CLL, in particular those with IGHV MUT. This trial was registered at www.clinicaltrials.gov as #NCT00281918. (Blood. 2016;127(2):208-215)

Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials

“…In a phase 1b/2 study of patients with CLL, 81% of 36 patients with del(17p) [relapsed/refractory (R/R) in 34 patients] achieved an objective response after ibrutinib treatment (Byrd et al , 2015). The median progression‐free survival (PFS) among the subgroup of patients with R/R del(17p) CLL was approximately 28 months (Byrd et al , 2015), which was substantially longer than the median PFS of approximately 11 months observed with either chemoimmunotherapy with FCR (fludarabine, cyclophosphamide and rituximab) (Fischer et al , 2016) or alemtuzumab (Hillmen et al , 2007) in first‐line patients. Consequently, ibrutinib was granted breakthrough therapy designation for del(17p) CLL and was given the first genotypic‐specific indication for the treatment of CLL patients, del(17p) CLL, in the United States in July 2014, and a similar indication in Europe in October 2014.…”

Ibrutinib in the real world patient: many lights and some shades

“…While a minority of patients may attain longlasting responses with chemoimmunotherapy, 3,4,5 relapse and treatment-resistant diseases develop in the majority of cases; infections, progressive disease and second primary tumors being the most frequent causes of death. 5 The firstin-class inhibitor of Bruton's tyrosine kinase (BTK), ibrutinib, was welcomed in 2013 as a new paradigm for the treatment of relapsed or refractory CLL, as it produced responses in 71% of the cases in a heavily pre-treated patient population who had few, if any, alternative treatment options. 6,7 After a median observation of 3 years, 8 exceptional overall survival (OS) and progression-free survival (PFS) rates were reported (79% and 69%, respectively), along with a low (12%) discontinuation rate due to adverse events.…”

Lymphome bei rheumatischen Erkrankungen

“…Die chronisch lymphatische Leukämie (CLL) zählt als reifzellige Lymphozytose zu den Non-Hodgkin-Lymphomen, sie ist die häufigste Leukämie mit einer Inzidenz von 4,2/100.000 Einwohner, das [17], bei >65-jährigen fitten Patienten kann auch BendamustinRituximab eingesetzt werden [14].…”