Most patients develop chronic lymphocytic leukemia (CLL) at an advanced age and already have clinically relevant comorbidities. Therefore, they have not yet been treated with intensive therapies. The standards were either indefinite therapy with targeted agents (eg, ibrutinib) or mild chemotherapy (chlorambucil) combined with an antibody (obinutuzumab).
The open and randomized international phase 3 CLL14 study under the direction of Univ.-Prof. Dr. Michael Hallek, head of the German Study Group on LLC, director of the Clinic I of Internal Medicine and the Center for Integrated Oncology (CIO) of the University of Cologne, was put developed in cooperation with Roche and tested a highly effective, time-limited and chemotherapy-free combination of a targeted drug (Venetoclax) with an antibody (obinutuzumab) against the old standard of chlorambucil-obinutuzumab. A total of 432 patients aged 41 countries of median age (between 41 and 89 years) were included in the study within one year.
They received either a six-month 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 increased by 67% the risk of disease progression or death compared with chlorambucil-obinutuzumab in patients with CLL never having treated and coexisting diseases (HR, 0.33, 95% CI, 0.22%). 0.51, p <0.0001). The overall response rate (ORR) was 85% (95% CI, 79% to 89%) with venetoclax-obinutuzumab vs 71% (95% CI, 65% to 77%) in the control group (P = 0.0007). The rate of complete remission (CR) or CR with incomplete hematologic recovery (CRi) was 50% compared to 23% (p <.0001).
In 57% of patients in the Venetoclax-Obinutuzumab group, residual residual bone marrow disease was no longer detectable; only 17% of patients in the chlorambucil-obinutuzumab group were treated. In peripheral blood, even 76% of patients were free of minimal residual disease (MRD-negative), compared to 35% in the chlormabucil arm. The combination of venetoclax and obinutuzumab has been approved by the US Food and Drug Administration (FDA) for the initial treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) on the based on the results of the CLL14 test.
"Patients who have never been treated for CLL have had to rely heavily on chemotherapy for initial treatment," says Hallek. "The approval of the Venetoclax combination means that patients with CLL and previously untreated comorbid conditions now have a timely, chemotherapy-free treatment option that allows them to perform deep molecular remissions. a long time without relapse and can complete treatment within twelve months.This is a huge step forward for these patients, "adds Professor Hallek.
The primary endpoint of the study was progression-free survival (PFS) assessed by the investigator; Secondary endpoints included PSS assessed by an independent review committee, minimal residual disease status, overall response rate, complete response rate, overall survival, duration of the study. response, event-free survival, processing time, and security.
The median duration of follow-up was 28 months (range 0.1 to 36 years). The median PFS was not reached in both arms. The safety assessment included 212 patients from the venetoclax arm and 214 patients from the control arm. The most common grade 3 adverse reactions observed with Venetoclax were haematological toxicity (60% versus 55% in the comparator group), most commonly neutropenia (53% versus 48% in the control group) and thrombocytopenia (14%). % vs. 15%). Other common adverse events were infections (18% vs. 15%) and infusion-related reactions (9% versus 10%). In the Venetoclax arm, adverse events led to dose interruption in 74% of patients, dose reduction in 21% of patients and discontinuation of treatment in 16% of patients.
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Fischer K, O Al-Sawaf, J Bahlo, Fink A-M, Tandon M, Dixon M, Robrecht S,
Warburton S, Humphrey K, O Samoylova, Liberati AM, Pinill Ibarz J, Opat S,
Sivcheva L, Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S,
Kipps TJ, Boettcher S, Exchange E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M and Hallek M. Venetoclax and Obinutuzumab in Patients with CLL and Coexising Conditions, N Engl J Med 2019,
DOI: 10.1056 / NEJMoa1815281
(Abstract ASCO 7502 J Clin Oncol 37, 2019, suppl; abstr 7502)