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Clinical Trial Report

Progress in the treatment of elderly/unfit chronic lymphocytic leukemia patients: results of the German CLL-11 trial

 

Abstract

Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia and affects mostly the elderly. Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab is generally considered a standard treatment for younger fit patients with CLL. In a recent randomized Phase III study of patients with newly diagnosed CLL and coexisting conditions, obinutuzumab, a humanized anti-CD20 glycoengineered type 2 antibody, used in combination with chlorambucil, demonstrated significant improvement in progression-free survival and several other outcome parameters, in comparison to rituximab plus chlorambucil. Grade 3–4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Results of this trial clearly established that obinutuzumab in combination with chlorambucil represent the new first-line standard of treatment in this setting. A broad range of novel agents with different mechanisms of action have already proven their efficacy in CLL. New drugs targeting specific molecular features, such as ibrutinib, idelalisib or ABT-199, are being tested at present, and their advent is very likely to change the future treatment paradigm of CLL that relies today on chemoimmunotherapy for both fit and elderly/unfit patients.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues
  • Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia that affects mostly elderly patients and is considered incurable without allogeneic transplantation.

  • Fludarabine, cyclophosphamide and rituximab chemoimmunotherapy which improves progression-free survival and overall survival is the standard of care for physically fit patients who need treatment.

  • The CLL-11 trial has established obinutuzumab in combination with chlorambucil as the new first-line standard of treatment for elderly CLL patients with comorbidities. In this setting, obinutuzumab clearly shows superiority over rituximab.

  • A broad range of novel agents with different mechanisms of action have already proven not only their efficacy but also a favorable safety profile. New drugs targeting specific molecular features such as ibrutinib, idelalisib or ABT-199 are tested at present and their advent is very likely to change the treatment paradigm of CLL which today relies on chemoimmunotherapy.

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