At the end of this year's Congress of the American Society of Oncology (ASCO) in Chicago, results of the primary endpoint analysis of the CLL14 study were presented for the first time. These are results that will change current medical approaches.
An important number of patients at an advanced age suffer from chronic lymphatic leukemia (CLL) and already have clinically relevant concomitant diseases at this time. Therefore, these patients have not yet been treated with intensive therapies. Instead, the standard was an unlimited therapy with targeted substances such as Ibrutinib or mild chemotherapy (e.g. Chlorambucil) in combination with an antibody (e.g. Obinutuzumab).
The open-label, randomized, international phase III CLL14 trial evaluated a highly potent, time-limited, and chemotherapy-free combination of a targeted drug (in this case: Venetoclax) with an antibody (in this case: Obinutuzumab) against the previous standard of Chlorambucil-Obinutuzumab. A total of 432 patients at a median age of 72 years were included in the study within one year.
Participants received either six months of treatment with Venetoclax-Obinutuzumab followed by six months of Venetoclax, or six months of treatment with Chlorambucil-Obinutuzumab followed by six months of Chlorambucil.
The results of the study showed that the Venetoclax combination reduced the risk of disease progression or death by 67% compared to Chlorambucil-Obinutuzumab in patients with treatment-naïve CLL and coexisting conditions (HR = 0.33; 95%-KI: 0.22-0.51; P < 0.0001). The overall response rate (ORR) was 85% (95%-KI: 79%-89%) with Venetoclax-Obinutuzumab versus 71% (95%-KI: 65%-77%) in the control arm (P = 0.0007). The rate of complete remissions (CR) or CR with incomplete hematologic recovery (CRi) was 50% versus 23% (P < 0.0001).
In 57% of the patients in the Venetoclax-Obinutuzumab arm, no minimal residual disease in the bone marrow could be detected, this was only the case in 17% of the patients in the Chlorambucil-Obinutuzumab arm. In peripheral blood, even 76% of patients were free of minimal residual disease (MRD-negative) compared to 35% in the Chlorambucil arm. The combination of Venetoclax and Obinutuzumab has now been approved by the U.S. Food and Drug Administration (FDA) for the initial treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) based on the results of the CLL14 study.
The median duration of the follow-up was 28 months (range 0.1-36). The median Progression-Free Survival (PFS) was not reached in both arms. The safety assessment included 212 patients on the Venetoclax arm and 214 patients on the control arm. The most frequent side effects from severity three were hematological toxicities for the combination with Venetoclax (60% compared to 55% in the comparison arm), the most frequent of which were neutropenia (53% compared to 48% in the control arm) and thrombocytopenia (14% compared to 15%). Other common side effects were infections (18% vs. 15%), infusion reactions (9% vs. 10%). In the Venetoclax arm, side effects led to dose interruptions in 74% of patients, dose reductions in 21% of patients, and treatment discontinuations in 16% of patients.