ASH 2013 - Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia

ASH 2013 Abstract 6: Head-To-Head Comparison Of Obinutuzumab (GA101) Plus Chlorambucil (Clb) Versus Rituximab Plus Clb In Patients With Chronic Lymphocytic Leukemia (CLL) and Co-Existing Medical Conditions (Comorbidities): Final Stage 2 Results Of The CLL11 Trial.
Valentin Goede et al.

Introduction: CLL11 is a large randomized phase 3 trial investigating first-line chemoimmunotherapy in CLL patients with comorbidities, i.e., patients typically treated in daily practice. Here, we present: 

  • The final stage II analysis with efficacy and safety results of the head-to-head comparison between GA101 plus Clb (GClb) and rituximab plus Clb (RClb); at the pre-planned interim analysis, the primary endpoint was met early and the results were released by the independent data monitoring board.
  • An update on the stage I analysis (GClb vs. Clb and RClb vs. Clb comparisons) with longer observation time; the final stage I analysis recently showed that GClb or RClb has superior efficacy to chemotherapy with Clb alone. 

Conclusions: GA101, a novel, glycoengineered, type 2 CD20 antibody, in combination with Clb (GClb regimen) demonstrated statistically significant and clinically meaningful prolongation of PFS, and higher complete response rate and MRD negativity rate compared with RClb in previously untreated CLL patients with comorbidities. Infusion-related reactions and neutropenia were more common with GClb without an increase in infections. Furthermore, GClb vs. Clb alone demonstrated a prolongation of OS. Overall, GClb is superior to RClb and a highly active treatment in this typical CLL patient population.

This study demonstrates that combining a type 2 CD20 antibody with chlorambucil improves response rates and PFS compared to rituximab in patients with CLL not eligible for first line FCR, without compromising safety. However, longer follow up is necessary to evaluate the full duration of response as well as the impact on overall survival. The cost effectiveness of this combination remains unclear.
— CARE Hematology Faculty

ASH 2013 Abstract 526: Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG). Barbara Eichhorst et al.

Introduction: FCR is the current standard first-line treatment regimen in advanced CLL (Hallek et al., Lancet, 2010), but is associated with significant side effects. The GCCLSG initiated an international phase 3 study in order to test the non-inferiority regarding efficacy and potentially better tolerability of BR compared to FCR in first-line therapy of physically fit pts without del(17p).

Conclusions: The results of this planned interim analysis show that FCR seems more efficient than BR in the first-line treatment of fit CLL pts with regard to higher CRR, as well as longer PFS and EFS. These advantages might be balanced by a higher rate of severe adverse events, in particular neutropenia and infections, associated with FCR. In light of these results, no firm recommendation of one regimen over the other can be given at the present time regarding the first-line use in CLL pts with good physical fitness.

In patients with indolent non-Hodgkin’s lymphoma, first-line BR improves response rates and progression-free survival compared to other rituximab containing chemotherapy regimens, as demonstrated in the Stil1 and BRIGHT trials. However, in the CLL10 trial, FCR had a higher response rate and PFS compared to BR, at the expense of higher greater toxicity. BR may be a reasonable alternative in selective patients with CLL.
— CARE Hematology Faculty