Jennifer Woyach, MD, a hematologist-oncologist and an associate professor within the Department of Internal Medicine at the Ohio State University Comprehensive Cancer Center –The James, discusses clinical trials examining novel triplet regimens in chronic lymphocytic leukemia (CLL).

Several ongoing cooperative group studies are of interest in CLL, says Woyach. These are National Clinical Trials Network trials and they are designed for frontline CLL. These efforts are similar to the previously conducted phase 3 E1912 study for younger patients with CLL and the AO41202 study for older patients with the disease.

These newer studies, EA9161 and AO41702, are designed to examine frontline treatment in younger and older patients with CLL. Both studies are comparing ibrutinib (Imbruvica) plus obinutuzumab (Gazyva) versus ibrutinib combined with both obinutuzumab and venetoclax (Venclexta) to see whether the strategy of adding venetoclax to an ibrutinib-based regimen improves progression-free survival in patients, says Woyach.

These studies are comparing a triplet regimen versus a doublet regimen and are a bit different in how they discontinue therapy in the triplet group. This research will be very helpful as we will be able to see how the benefits seen with a triplet versus a doublet extend to both older and younger patient populations, concludes Woyach.

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Jennifer Woyach, MD, discusses clinical trials examining novel triplet regimens in chronic lymphocytic leukemia.

Dr. Woyach on Clinical Trials Examining Novel Triplets in CLL

Jennifer Woyach, MD, a hematologist-oncologist and an associate professor within the Department of Internal Medicine at the Ohio State University Comprehensive Cancer Center–James, discusses the safety profile of acalabrutinib (Calquence) compared with ibrutinib (Imbruvica) in chronic lymphocytic leukemia (CLL). 

The safety profile of acalabrutinib in CLL looks very promising, says Woyach. The rates of some of the toxicities that are associated with BTK inhibitors, such as atrial fibrillation, are relatively infrequent with acalabrutinib; however, this is probably seen a bit more with acalabrutinib than ibrutinib in the general population, notes Woyach. 

Hypertension appears to be observed less with acalabrutinib, although it took several clinical trials, patients, and time to identify hypertension as a toxicity for ibrutinib, admits Woyach. 

Some of the milder toxicities such as arthralgias and bruising appear less, as well, according to Woyach. Significant bleeding is also very rare with both agents, but it does not look like it is seen more with acalabrutinib compared with ibrutinib, concludes Woyach.

Jennifer Woyach, MD, discusses the safety profile of acalabrutinib compared with ibrutinib in chronic lymphocytic leukemia. 
 

Dr. Woyach on the Safety of Acalabrutinib Versus Ibrutinib in CLL

Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses the role of acalabrutinib (Calquence) in chronic lymphocytic leukemia (CLL). 

Acalabrutinib is a second-generation BTK inhibitor and, similar to ibrutinib (Imbruvica), it binds irreversibly to BTK, says Woyach.

Although ibrutinib inhibits several proteins that are similar in structure, acalabrutinib is more selective, which may mitigate toxicity. 

According to mature results from the phase 2 ACE-CL-001 trial (NCT02029443), acalabrutinib continued to show encouraging clinical activity in patients with treatment-naïve CLL. 

At a median follow-up of 53 month​s, 86% of patients were still receiving treatment, and the event-free survival rate at 48 months was 90%, which is similar to ibrutinib, Woyach concludes.

Jennifer Woyach, MD, discusses the role of acalabrutinib in chronic lymphocytic leukemia. 







Dr. Woyach on the Role of Acalabrutinib in CLL 

Jennifer Woyach, MD, a hematologist-oncologist and an associate professor within the Department of Internal Medicine at the Ohio State University Comprehensive Cancer Center–James, discusses remaining sequencing questions within the field of chronic lymphocytic leukemia (CLL).

Several updates have recently read out in the frontline CLL space, says Woyach. For example, results from the phase 3 CLL14 study with venetoclax (Venclexta) plus obinutuzumab (Gazyva) have been shared, as well as updates on studies examining acalabrutinib (Calquence) or ibrutinib (Imbruvica), where the most long-term data exist, according to Woyach.

One question that still needs to be addressed in this space is, Does it matter how these novel therapies are sequenced? Most of the available trial data are on patients who come off of a BTK inhibitor and then are treated with venetoclax. It has always been a question as to whether a patient could successfully transition from venetoclax to a BTK inhibitor. No prospective data are available in that setting, but accumulating data from retrospective studies suggest that this could be a very successful strategy. Most patients who are treated with venetoclax and relapse on or after treatment can successfully be treated with a BTK inhibitor, concludes Woyach.

Jennifer Woyach, MD, discusses remaining sequencing questions within the field of chronic lymphocytic leukemia.

Dr. Woyach on Remaining Sequencing Questions in CLL

Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses the role of small molecule inhibitors in chronic lymphocytic leukemia (CLL).

Most patients with CLL receive treatment with small molecule inhibitors throughout the entire course of their disease, says Woyach. 

Standard treatment​s include ​BTK inhibitors such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa)​, explains Woyach. In addition, venetoclax ​(Venclexta), a BCL​-2 inhibitor, in combination with obinutuzumab (Gazyva) or rituximab (Rituxan) is another option in the space. 

Moreover, reversible BTK inhibitors have shown encouraging preliminary efficacy ​in CLL, Woyach concludes. 

Jennifer Woyach, MD, discusses the role of small molecule inhibitors in chronic lymphocytic leukemia.

Dr. Woyach on the Role of Small Molecule Inhibitors in CLL 

Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses ​the role of chemoimmunotherapy in chronic lymphocytic leukemia (CLL).

Recently, multiple positive phase 3 clinical trials have ​demonstrated superiority with novel agents compared with chemoimmunotherapy in CLL, says Woyach. In the clinic, the benefits and risk​s associated with chemoimmunotherapy, BTK inhibitors, and B​CL​-2 inhibitors must be discussed in great detail

Although FCR chemoimmunotherapy remains a standard treatment option for young, fit patients who do not have concerning genomic abnormalities, the regimen is being utilized less in the clinic. Moreover, patients tend to prefer alternative options, Woyach concludes. 

Jennifer Woyach, MD, discusses ​the role of chemoimmunotherapy in chronic lymphocytic leukemia.

Dr. Woyach on the Role of Chemoimmunotherapy in CLL  

Jennifer A. Woyach, MD, an associate professor of Medicine in the Division of Internal Medicine at The Ohio State University Comprehensive Cancer Center, discusses a phase II trial of the CD19-directed antibody MOR208 in combination with lenalidomide (Revlimid) or ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia (CLL).

MOR208 is clinically engineered to improve Fc-gamma receptor binding, Woyach explains. Prior phase I findings demonstrated that the novel agent has efficacy in CLL and is also safe. In the phase II trial, researchers combined MOR208 with lenalidomide due to the preclinical data showing that lenalidomide can increase natural killer cells in antibody-dependent cell-mediated cytotoxicity, she adds.

The study also enrolled 4 cohorts: relapsed/refractory CLL, treatment-naïve CLL, Richter's transformation, and those who received prior treatment with ibrutinib. Additionally, the cohort of prior ibrutinib treatment are of patients who developed mutations that would render them resistant to ibrutinib, such as 

Jennifer A. Woyach, MD, an associate professor of Medicine in the Division of Internal Medicine at The Ohio State University Comprehensive Cancer Center, discusses a phase II trial of the CD19-directed antibody MOR208 in combination with lenalidomide (Revlimid) or ibrutinib (Imbruvica) in patients with CLL.

Jennifer A. Woyach, MD

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