Jennifer Woyach, MD

Jennifer Woyach, MD, an associate professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center–James, discusses the rationale and efficacy for the phase 1/2 trial of acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL).

Woyach explains that acalabrutinib is an inhibitor of Bruton’s kinase (BTK), and it's a second-generation covalent inhibitor. Similar to ibrutinib (Imbruvica), it binds irreversibly to BTK, but it is more selective than ibrutinib. Ibrutinib inhibits many structurally similar proteins, while acalabrutinib inhibits less, which is important for toxicity. She thinks that some of the toxicity seen with ibrutinib are because of those alternative targets. Some of the toxicities may lessen with acalabrutinib.

In treatment-naïve and relapsed/refractory disease, the data has looked promising with this agent, according to Woyach. In 1 study with 53 months of follow-up for 99 patients with treatment-naïve CLL, about 86% of the patients were still on treatment, which she says is impressive. The event-free survival at 48 months was 90%. This is looking promising with acalabrutinib, which is similar to what has been seen with ibrutinib in this patient population. Although she says it’s difficult to compare trial to trial, it’s good to see that it looks similar to ibrutinib in this setting.

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Jennifer Woyach, MD, discusses the rationale and efficacy for the phase 1/2 trial of acalabrutinib in patients with chronic lymphocytic leukemia.

Acalabrutinib Shows Promising Results for the Treatment of CLL

Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses the adverse events (AEs) that differentiate the toxicity profiles of the treatments that are available in the frontline setting for patients with chronic lymphocytic leukemia (CLL).

With BTK inhibitors, specifically ibrutinib (Imbruvica), the long-term safety profiles are known, Woyach notes. The toxicities of concern with these therapies include atrial arrhythmias, which occurs in about 10% to 15% of patients with CLL. Grade 3 or greater hypertension can also occur, but that happens more frequently with longer duration of therapy. Other AEs that are less dangerous but more common include arthralgias, fatigue, and upper-respiratory infections.

Atrial arrythmias may be seen with acalabrutinib (Calquence), another BTK inhibitor, but it appears to be less frequent than with ibrutinib, Woyach says. There also appears to be less bruising and less arthralgias with acalabrutinib as well. Acalabrutinib is associated with headache, but it is predominantly low grade and goes away over time.

Venetoclax (Venclexta) is associated with neutropenia, especially early on in patients with CLL. There is also risk of tumor lysis syndrome, particularly among those with the first ramp-ups. The primary concerns with chemoimmunotherapy are cytopenias, which can occur both during and prolonged after treatment. Woyach also notes that patients treated with fludarabine, cyclophosphamide, and rituximab (Rituxan) have almost a 5% risk of myelodysplastic syndrome or acute myeloid leukemia.

Jennifer Woyach, MD, discusses the adverse events that differentiate the toxicity profiles of the treatments that are available in the frontline setting for patients with chronic lymphocytic leukemia.

Comparing Toxicity Profiles of Available Frontline Agents in CLL

Jennifer Woyach, MD, an associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer CenterJames, discusses the frontline options for the treatment of patients with chronic lymphocytic leukemia (CLL).

There are a number of options in the first-line setting for patients with CLL, Woyach says. In terms of targeted therapies, ibrutinib (Imbruvica) can be used on its own as a single agent and most often is. However, acalabrutinib (Calquence), another BTK inhibitor, can be used with or without Obinutuzumab (Gazyva). There is also data on venetoclax (Venclexta) in combination with obinutuzumab.

Chemoimmunotherapy options are still considered, such as the fludarabine, cyclophosphamide, and rituximab (FCR) regimen. FCR is considered especially for younger patients with IGVH-mutant CLL. Bendamustine/rituximab and chlorambucil/obinutuzumab are also still available, but Woyach says there are not a lot of scenarios where these would be used now.

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Jennifer Woyach, MD, discusses the frontline options for the treatment of patients with chronic lymphocytic leukemia.

Frontline Treatment Options Available for Patients With CLL

Jennifer Woyach, MD, associate professor, Ohio State University, discusses a study combining MOR208 with Lenalidomide for the treatment of chronic lymphocytic leukemia (CLL).&nbsp;

An Overview of a Study Combining MOR208 With Lenalidomide in CLL

Jennifer Woyach, MD, assistant professor of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, discusses the association of disease progression on ibrutinib therapy with the acquisition of resistance mutations as seen at The Ohio State University Comprehensive Cancer Center.

Researchers found that the 267 patients that were treated with ibrutinib at The Ohio State University Comprehensive Cancer Center had a low rate of relapse.

29 patients were in total relapse with a median follow-up of 20 months. Of those 29 patients, 17 relapsed with Richter's transformation while the other 12 relapsed with CLL.

Patients who relapsed with CLL also had BTK and PLCÎ³2 mutations that were not present at baseline.

Only 2 out of 8 patients tested who relapsed with Richterâ€™s transformation had mutations in BTK or PLCÎ³2.

Further research is being conducted to look into the associated between Richterâ€™s transformation and BTK and PLCÎ³2 mutations.

Progression on Ibrutinib With the Acquisition of Resistance Mutations

Jennifer Woyach, MD, assistant professor of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, discusses the efficacy findings from the RESONATE trial, a phase III trial that compared ibrutinib versus ofatumumab in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma.

The results of the study showed that the efficacy of ibrutinib was much superior to that of ofatubumab.

The study also showed response rates were significantly better with ibrutinib [ORR=42.6 vs 4.1% (P <0.0001), ORR+PR with lymphocytosis=62.6 vs 4.1%]

Progression-free survival was not yet reached in the ibrutinib arm but was about 8.1 months in the ofatumumab arm.

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Jennifer Woyach, MD | Authors

Articles

Acalabrutinib Shows Promising Results for the Treatment of CLL

Comparing Toxicity Profiles of Available Frontline Agents in CLL

Frontline Treatment Options Available for Patients With CLL

An Overview of a Study Combining MOR208 With Lenalidomide in CLL

Progression on Ibrutinib With the Acquisition of Resistance Mutations

Efficacy Findings from the RESONATE Trial