Increased rituximab exposure does not improve response and outcome of patients with chronic lymphocytic leukemia after fludarabine, cyclophosphamide, rituximab. A French Innovative Leukemia Organization (FILO) study

Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first‐line immunochemotherapy

“…Likewise, exposure‐response analyses of trastuzumab treatment in patients with HER2+ cancers have suggested that patients with low drug exposures had shorter overall survival times; however, increasing the dose did not lead to an improvement in efficacy . Similar results have been found in CLL and DLBCL patients treated with dose dense treatment regimens of rituximab . Recently, a Food and Drug Administration pharmacometric reviewer highlighted the complexity of such analyses: “When both the response and the drug target can affect the exposure, the causal relationship between the two becomes confounded.…”

Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial

“…The 62% efficacy rate was high, especially since calculated by ITT (85 of all 135 patients enrolled), and more than double that typically reported for six cycles of FCR (under 30%); the primary objective was thus exceeded by far. [3][4][5][6]8 The rate is superior to that reported for any first-line regimen based on chemotherapy plus rituximab. [3][4][5][6][7]8,25 A feature of our experimental strategy is that patients received study treatment for a definite period of time (total 15 months).…”

“…[3][4][5][6]8 The rate is superior to that reported for any first-line regimen based on chemotherapy plus rituximab. [3][4][5][6][7]8,25 A feature of our experimental strategy is that patients received study treatment for a definite period of time (total 15 months).…”

“…A total of 49 SAE were observed (27 part 1; 22 part 2) (appendix p 3). Most frequent categories of SAE were infections (10 events), cardiac events (8), and haematological events (8).…”

“…1,[3][4][5][6][7] However, irrespective of the clinical response status, CLL cells can often remain in the peripheral blood and/or bone marrow, and reported rate of CR with bone marrow MRD <0•01% with FCR is typically under 30%. [3][4][5][6]8 Presence of residual CLL cells has demonstrated associations with poorer progression-free survival (PFS) 4,5,7,9 and overall survival (OS). 4,5,7 This suggests that detection of minimal residual disease (MRD) has powerful value as a prognostic factor and as a PFS surrogate primary endpoint in clinical trials.…”