CLL – Page 7 – New Developments in Lymphoma

Acalabrutinib for Patients with Previously Untreated Chronic Lymphocytic Leukemia

Acalabrutinib is a second generation Bruton’s tyrosine kinase (BTK) inhibitor that targets the B-cell receptor signaling and is considered a prime target for the treatment of CLL. Acalabrutinib inhibits BTK activity preventing the activation of the B-cell antigen receptor pathway, and leads to CLL cell death. Recently at the 2016 ASCO annual meeting researchers presented preliminary results from an ongoing phase 1-2 study using acalabrutinib to treat patients with previously untreated CLL. Of the 74 patients enrolled in the trial 72 were evaluable for response. Acalabrutinib was well tolerated, with 72 of 74 patients remaining on treatment at time of analysis and evaluable for response. Neither of the two patients discontinued treatment for drug related adverse events.

The most common side effects were headaches, diarrhea, arthralgia, contusion, nausea, and weight increase, all characterized as mild. Treatment related lymphocytosis occurred in 53% of patients and was resolved in 97% of the affected patients at a median of 7 weeks. Patients who took acalabrutinib experienced a 96% overall response rate (PR=86%, PR-L=10%) with the median time to response being 2-8 months. For patients with untreated CLL the initial safety profile and high response rates are promising. Based on these results a phase 3 trial of acalabrutinib versus ibrutinib has commenced to further study the use of acalabrutinib in the treatment of patients with CLL.

Mathematical Analysis of Drug Resistance in CLL

According to a recent study published in Nature Communications by Weill Cornell Medicine investigator Dr. Dan Avi Landau the rate at which genetically mutated cancer cells grow could be a key to explaining why some CLL patients develop resistance to treatment. Dr. Landau’s findings demonstrate how an individual’s cell mutations can influence that individual’s response to treatment, leading to the development of resistance to treatments like ibrutinib. CLL patients who are treatment resistant require treatment strategies that take account of their treatment resistance. Using mathematical modeling researchers investigated how:

“…some patients with chronic lymphocytic leukemia (CLL)…become resistant to the drug ibrutinib, which is used to treat the disease once other chemotherapy drugs have failed. They performed mathematical modeling of the growth rates of the sensitive and resistant cells, and discovered that a small cluster of cancer cells survived ibrutinib therapy due to a genetic mutation that was present prior to treatment, allowing these ibrutinib-resistant cells to multiply and the disease to progress unabated. The findings could offer scientists a framework to guide the development of combination therapies that overcome drug resistance in CLL and in other cancers.”

These findings could potentially allow for physicians to develop more precise treatment plans for patients. In theory physicians could be more easily able to treat their patients not just for their present conditions, but also take into account their future conditions.