The 2021 Society for Hematological Oncology (SOHO) Annual Meeting took place last month from September 8-11, 2021. During the meeting, researchers discussed new advances in the field of hematology. According to Cancer Network, one such discussion centered around the efficacy of pirtobrutinib (LOXO-305) for patients with previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). In Abstract CLL-039, researchers explored data from the Phase 1/2 BRUIN clinical trial to show how pirtobrutinib treatment improved patient outcomes.
Pirtobrutinib
To begin, what exactly is pirtobrutinib? According to LOXO Oncology at Lilly, pirtobrutinib is:
an investigational, oral, highly-selective non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells.
Within the Phase 1/2 BRUIN clinical trial, researchers evaluated pirtobrutinib as a therapeutic option for patients with previously treated CLL and SLL. Patients in the trial had previously been treated with therapies such as BTK inhibitors, PI3K inhibitors, CAR T-cell therapy, anti-CD20 antibodies, BCL-2 inhibitors, chemotherapy, allogenic stem cell transplants, and lenalidomide. Even though pirtobrutinib is a BTK inhibitor, 67% of patients had previously stopped taking BTK inhibitors due to disease progression. During the initial stage of this trial, patients received between 25-300mg pirtobrutinib each day. However, during the Phase 2 portion, 200mg daily was used.
Findings from the study include:
- The overall response rate (ORR) for patients previously treated with BTK inhibitors was 62%, with 34% of patients achieving a stable disease state. Additionally, this response rate grew to 86% after a 10-month treatment period.
- Pirtobrutinib showed a sustained and durable response, highlighting how it can benefit patients over a longer time period.
- Out of all included patients, only 5 left the trial due to adverse reactions.
- Despite this, pirtobrutinib was relatively safe and well-tolerated. Side effects included fatigue, diarrhea, bruising, rash, high blood pressure, hemorrhage, joint pain, and atrial fibrillation.
Chronic Lymphocytic Leukemia (CLL)
In chronic lymphocytic leukemia (CLL), a blood and bone marrow cancer, the bone marrow produces abnormal lymphocytes, a type of white blood cell. Normally, lymphocytes help the body fight infections. However, in patients with CLL, the abnormal lymphocytes crowd healthy blood cells out of the bone marrow, causing issues. CLL is considered the second most common form of adult leukemia. Symptoms include fatigue, fever and night sweats, an enlarged spleen, abdominal pain, unintended weight loss, frequent infections, and enlarged – but painless – lymph nodes.
Small Lymphocytic Lymphoma (SLL)
Small lymphocytic lymphoma (SLL) is often considered the same as, or very similar to, CLL. While patients with CLL have abnormal lymphocytes in the blood and bone marrow, these abnormal lymphocytes are found in lymph nodes in SLL. This rare cancer is considered a form of non-Hodgkin’s lymphoma. Chemotherapy, pesticide exposure, and being immunocompromised increase the risk of developing SLL. Symptoms include fever and night sweats, unintended weight loss, fatigue, easy bruising and bleeding, shortness of breath, abdominal inflammation and tenderness, a feeling of fullness, and painless swelling in the armpit, groin, and neck.
