The U.S. Food and Drug Administration ( FDA ) has approved Venclexta ( Venetoclax ) in combination with Obinutuzumab ( Gazyva ) for previously untreated patients with chronic lymphocytic leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ).
The FDA granted Breakthrough Therapy designation for this combination therapy, and early submission of the data was provided under the Real-Time Oncology Review ( RTOR ) pilot program, which led to approval in just over two months, following submission of the complete application.
The CLL14 trial has demonstrated superior progression-free survival as assessed by an independent review committee ( PFS; the time from initiation of treatment until disease progression or death ) in patients treated with Venetoclax plus Obinutuzumab compared to patients who received Chlorambucil plus Obinutuzumab, a commonly used standard of care.
With a median follow-up of 28 months ( range: 0.1 to 36 months ),Venetoclax plus Obinutuzumab has reduced the risk of progression or death by 67% compared with Chlorambucil plus Obinutuzumab ( hazard ratio, HR=0.33, 95% confidence interval [ CI ]: 0.22, 0.51; p less than 0.0001 ).
Median PFS was not reached in either treatment arm.
Minimal residual disease ( MRD ) negativity ( undetectable disease in the blood or bone marrow ) was assessed as a secondary endpoint and occurs when less than one CLL cell per 10,000 leukocytes can be detected using sensitive analytical methods.
Higher rates of MRD negativity were observed with Venetoclax plus Obinutuzumab compared to Obinutuzumab plus Chlorambucil in both bone marrow ( 57% versus 17%, p less than 0.0001 ) and peripheral blood ( 76% versus 35%, p less than 0.0001 ) three months after treatment completion.
In the CLL14 trial, adverse events were consistent with the known safety profiles of Venetoclax and Obinutuzumab alone.
Serious adverse reactions were reported in 49% of patients in the Venetoclax plus Obinutuzumab arm, most often due to febrile neutropenia and pneumonia ( 5% each ).
The most common serious adverse reactions ( greater than or equal to 15% ) of any grade were neutropenia ( 60% ), diarrhea ( 28% ), fatigue ( 21% ), nausea ( 19% ), anemia ( 17% ), and upper respiratory tract infection ( 17% ).
Venetoclax is an oral B-cell lymphoma-2 ( BCL-2 ) inhibitor. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis.
Venetoclax targets the BCL-2 protein and works to help restore the process of apoptosis.
CLL is typically a slow-progressing cancer of the bone marrow and blood in which types of white blood cells called B lymphocytes become cancerous and multiply abnormally.
In the U.S., CLL accounts for more than 20,000 newly diagnosed cases of leukemia each year. ( Xagena )
Source: Abbvie, 2019