Skip to main content
  • Advertise
    Want to Advertise with Us?
    Conquer welcomes advertising and sponsorship collaborations with reputable companies offering high-quality products and services to people affected by cancer.
  • Affiliated Brands
    Academy of Oncology Nurse & Patient Navigators
    The Academy of Oncology Nurse & Patient Navigators (AONN+) is the largest national specialty organization dedicated to improving patient care and quality of life by defining, enhancing, and promoting the role of oncology nurse and patient navigators. Our organization of over 8,900 members was founded in May 2009 to provide a network for all professionals involved and interested in patient navigation and survivorship care services to better manage the complexities of the cancer care treatment continuum for their patients. We view our organization as one consisting of “professional patient advocates” and, to that end, we support and serve our members.
    Journal of Oncology Navigation & Survivorship
    The Journal of Oncology Navigation & Survivorship (JONS) promotes reliance on evidence-based practices in navigating patients with cancer and their caregivers through diagnosis, treatment, and survivorship. JONS also seeks to strengthen the role of nurse and patient navigators in cancer care by serving as a platform for these professionals to disseminate original research findings, exchange best practices, and find support for their growing community.
    The Oncology Nurse-APN/PA
    The Oncology Nurse-APN/PA (TON) provides coverage of the wide spectrum of oncology-related events, trends, news, therapeutics, diagnostics, organizations, and legislation that directly affect hematology/oncology nurses and advanced practitioners involved in healthcare delivery and product utilization. The scope and coverage include a unique presentation of news and events that are shaping the care of patients with cancer.
  • Healthcare Providers
  • Contribute

Triplet Regimen with Acalabrutinib Is Highly Active in Untreated Chronic Lymphocytic Leukemia

Web Exclusives — December 9, 2019

A 3-drug combination of acalabrutinib, venetoclax, and obinutuzumab, known as AVO, proved to be highly active as frontline therapy for patients with chronic lymphocytic leukemia (CLL) in a new study.

In the single-arm phase 2 study, nearly half (48%) of the patients who were treated with AVO had undetectable disease in their bone marrow after only 8 monthly cycles of therapy. By cycle 16, 75.0% had undetectable disease in their bone marrow, reported Benjamin L. Lampson, MD, PhD, at the 2019 meeting of the American Society of Hematology in Orlando, FL.

The safety profile of the AVO triplet was favorable. Notably, the rate of infusion-related reactions was markedly lower with AVO when compared with historical data for obinutuzumab given alone or with chemotherapy.

In addition, pretreatment with acalabrutinib and obinutuzumab reduced the risk for tumor lysis syndrome (TLS) that is often seen when venetoclax is administered, said Dr. Lampson, medical oncologist at Dana-Farber Cancer Institute, Boston, MA.

Because acalabrutinib, obinutuzumab, and venetoclax work via nonoverlapping mechanisms and have nonoverlapping toxicities, said Dr. Lampson, “it makes sense to ask, can we combine them to achieve even deeper, more durable remissions in CLL?”

A different triplet regimen of ibrutinib, venetoclax, and obinutuzumab is effective in CLL but “the rate of infusion-related reactions was high and the adverse event list is dominated by side effects that we have come to associate with ibrutinib, including bruising, hypotension, and joint pains,” said Dr. Lampson.

Therefore, the AVO regimen studied is an attempt to achieve the benefit of triplet therapy while avoiding some of its side effects, he said.

The study enrolled 37 patients with confirmed, previously untreated CLL. Acalabrutinib, venetoclax, and obinutuzumab were started sequentially, with a 28-day cycle lead-in with acalabrutinib followed by 6 cycles of obinutuzumab. Venetoclax was added at cycle 4. Combination therapy continued for a total of 15 cycles.

Pretreatment with acalabrutinib and obinutuzumab was able to mitigate venetoclax-associated TLS, said Dr. Lampson. At baseline, 98% of patients were considered to be at either medium or high risk for TLS. When TLS risk was assessed by computed tomography and complete blood counts prior to venetoclax, 89% of patients were considered to be at low risk for TLS.

Prior to venetoclax administration, 97% of patients achieved a response, all of which were considered to be partial responses. At cycle 8, after completion of obinutuzumab, the response rate was 100%, 25% of which were complete responses.

At cycle 8, 68% of patients had undetectable disease in their blood, and 17% of patients had a complete response with undetectable disease in their bone marrow. The rates of undetectable disease appear to increase over time, said Dr. Lampson.

Neutropenia was the most frequent hematologic toxicity. The most common nonhematologic toxicities were fatigue (84%), headache (76%), and bruising (46%).

The acalabrutinib dose had to be reduced due to headache in 2 patients. Venetoclax dose reduction was required in 1 patient due to grade 4 neutropenia. One patient with preexisting gastrointestinal symptoms discontinued all study medications.

Recommended For You