Targeted Agents Shift the Landscape of CLL Treatment

Strides have been made for the frontline treatment of patients with chronic lymphocytic leukemia (CLL), such as the shift from chemo immunotherapy to targeted agents, which have improved outcomes in this patient population.

With these specific treatments, quality of life has improved as well.

Dr. Seema Bhat, associate professor at The Ohio State University College of Medicine, presented findings of frontline therapy in patients with CLL at the Educated Patient® CLL Summit.

The presentation focused on the frontline treatment in patients with CLL.

Notably, all patients aren’t in need of treatment when they are diagnosed; patients who are in the early stages of their diagnosis and don’t have any early signs of disease may undergo observation, but might not require treatment. These patients are typically observed every couple of months,to check on specific symptoms and complete blood work, according to Bhat.

“On blood work, we pay more attention to the hemoglobin and the platelets. If they are going in reverse direction (they’re going down), then we are concerned and if any of these is changing, patients go to the next phase that starting treatment. If none of this is happening, patients continue with the observation and that can continue for a long time. But if at any point that changes, if patients have any disease related signs and symptoms fevers, chills, night sweats, unintentional weight loss, bulky lymph nodes, which are symptomatic, spleen, hemoglobin dropping or platelets dropping, then we call them the classic International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for treatment, then we consider those patients candidates for treatment and talk about treatment at that time,” explained Bhat.

Over the last couple of decades, the treatment paradigm has shifted in CLL, explained Bhat.

“A decade ago, frontline therapy was basically immunotherapy chemotherapy combined with (Rituximab [rituximab]) for younger patients — and by younger patients in the CLL field, meaning than 65 years of age (or younger). They were given a regimen called fludarabine, cyclophosphamide and (Rituxan) (FCR) and those older than 65 were given Treanda (bendamustine) plus (Rituxan), that was the standard treatment. And around the beginning of the 2010 decade, clinical trials were being conducted with BTK inhibitors and (Imbruvica [ibrutinib] . People are seeing phenomenonal responses in patients and that led to frontline treatments with these agents, which were actually compared to standard frontline chemo immunotherapies, both in the younger patients and older patients and in both the populations, the frontline beat chemo immunotherapy and that’s what is the standard now,” explained Bhat.

What used to be chemo immunotherapy treatment has turned into targeted agents, such as BTK and BCL2 inhibitors. These oral home-based regimens have led to improved responses and survival in patients with CLL and have improved quality of life as well, according to Bhat.

“We have these BTK inhibitors, which were compared head-to-head with these standard chemo immunotherapies. And then we also have another agent (Venclexta [venetoxlax]), which is a BCL2 inhibitor, which is given in combination with a monoclonal antibody and ICD 20, monoclonal antibody affinity of the map. And the difference is that here, it’s a fixed duration one year treatment compared to BTK inhibitors, which are indefinite,” explained Bhat.

Even with these improvements, researchers are still focusing on improving the frontline of treatment to better patients with CLL.

“One of the regiments, (Imbruvica) plus (Venclexta) has already been approved in Europe. And we are hoping that it will be approved through then in the United States, but there are multiple other clinical trials, similar clinical trials still ongoing,” stated Bhat.

Physicians and patients should discuss other diseases and risk factors when determining a treatment plan.

“We can guide the patient, knowing which treatment will be best for that particular patient, and we are moving more towards a personalized care for the patient. And that’s where shared decision making is very important that patients should be aware of the disease, ask appropriate questions and we work as a team,” Bhat noted.

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