Evaluating the safety and effectiveness of ibrutinib lead-in treatment before venetoclax initiation in reducing tumor size in patients with chronic lymphocytic leukemia.

This study investigated the safety and effectiveness of ibrutinib (Imbruvica) lead-in treatment before venetoclax (Venclexta) initiation for reducing tumor size in patients with chronic lymphocytic leukemia (CLL). The data showed that three cycles of ibrutinib lead-in treatment before venetoclax initiation significantly reduced the tumor size, decreased the risk of tumor lysis syndrome (TLS), and reduced the need for hospitalization for intensive monitoring for TLS in these patients.

CLL is a type of cancer that affects the blood and bone marrow. Ibrutinib and venetoclax are targeted therapies that work by blocking the growth of cancer cells. Both targeted therapies are commonly used in the treatment of CLL and improve survival. However, when taken alone only a few patients achieve undetectable minimal residual disease (MRD) response rates and need to be taken indefinitely. MRD is the small number of cancer cells that remain after treatment. The treatment goal is undetectable MRD.

Recent studies have shown that combining ibrutinib and venetoclax demonstrated high undetectable MRD response rates in both blood and bone marrow in patients with CLL. However, the safety and effectiveness of ibrutinib lead-in treatment before venetoclax initiation in reducing tumor size in patients with CLL is still unknown.

This study involved 323 patients with CLL who received 3 cycles of ibrutinib (for reducing tumor before other treatment; lead-in treatment) followed by 12 cycles of combined ibrutinib plus venetoclax.

The percentage of patients with a lymph node diameter of 5 cm or larger decreased from 31% at the start of treatment to 4% after ibrutinib lead-in treatment.

The percentage of patients with an absolute lymphocyte (white blood cell) count of 25 × 109 /L or higher decreased from 76% at the start of treatment to 65% after ibrutinib lead-in treatment.

The percentage of patients whose risk for tumor lysis syndrome (TLS) was high decreased from 23% at the start of treatment to 2% after ibrutinib lead-in treatment. TLS occurs when a large number of cancer cells are killed at once and their byproducts enter the bloodstream. If left untreated, TLS can lead to acute kidney failure, heart rate problems, neurological complications, and seizures.

The need for hospitalization (due to high TLS risk, or medium TLS risk and creatinine clearance – a measure of kidney function – less than 80 mL/min) decreased from 43% at the start of treatment to 18% after ibrutinib lead-in treatment.

This study concluded that three cycles of ibrutinib lead-in treatment before venetoclax initiation reduced the tumor size, decreased the risk of TLS and reduced the need for hospitalization for intensive monitoring for TLS in patients with CLL.

This study was funded by Janssen Pharmaceuticals and Pharmacyclics, the manufacturers of ibrutinib and venetoclax.