Front-Line Imbruvica-Venclexta Combo May Induce Durable Responses in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

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Treatment with this combination was associated with encouraging clinical responses in this patient population.

Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) achieved adequate responses to the first-line treatment of Imbruvica (ibrutinib) plus Venclexta (venetoclax), according to recent findings.

Data from the phase 2 CAPTIVATE study, which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that treatment with the combination was similarly associated with high rates of overall survival (time from diagnosis or treatment start when patients are alive) and progression-free survival (time during and after treatment when the patient lives without disease progression).

The data presented at the ASCO Annual Meeting focused on the fixed-duration treatment group of the CAPTIVATE study, with patients receiving three cycles of Imbruvica followed by 12 cycles of Imbruvica plus Venclexta. A total of 159 previously untreated patients with CLL and SLL aged 70 years or younger with an ECOG performance score (a patients level of functioning and ability to care for themselves with 0 being fully active and 4 being disabled) of 0 to 2 were enrolled onto the trial.

Ninety-two percent of the patients completed the 12 cycles of Imbruvica plus Venclexta. The median time on study was 27.9 months with a median treatment duration of 13.8 months. The median follow-up was 14.0 months after treatment completion

In patients whose disease did not harbor a deletion 17p mutation, the combination induced a complete response rate of 56% and 55% in the all-treated patient population. The only exception was observed in the bulky disease category, where patients with bulky disease had a complete response rate of 31%.

Further, for patients with bone marrow or peripheral disease, high rates of undetectable minimal residual disease (a small number of cancer cells that could be detected during or after treatment) were observed, including in patients with high-risk disease features.

When examining patients at 24 months, those without the deletion 17p mutation treated with the combination had a 96% progression-free survival rate. For overall survival, the 24-month rate was 98% in the same patient population. The median follow-up time was 27.9 months.

The most common side effects of any severity in the combination treatment group were diarrhea (62%), nausea (43%), neutropenia (low count of neutrophils or white blood cells; 42%), and joint pain (33%). Serious or severe side effects included neutropenia (33%), infections (8%), hypertension (6%), and neutrophil count decrease (5%). Twenty-three percent of patients experienced any serious side effect, with only one f death occurring.

“All of these results together support the idea of the combination of (Imbruvica) plus (Venclexta) as an all-oral, once daily, chemo(therapy)-free, fixed-duration (treatment) that may achieve deep responses and undetectable (minimal residual disease) in a vast majority of patients,” lead study author Dr. Paolo Ghia, of the Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele in Milan, Italy explained during a presentation of the findings.

This combination therapy is currently being examined in a complementary older population in a phase 3 trial, the results of which are expected soon.

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