An ‘Equal Playing Field’ Makes up the Available Treatment Options for CLL

A few years ago, oncologists often treated newly diagnosed patients with chronic lymphocytic leukemia (CLL) with a multitude of chemoimmunotherapy regimens.

However, as one hematologic oncologist recently noted, this trend has shifted tremendously to a point where there’s very little use for chemoimmunotherapy regimens in this patient population.

In fact, targeted therapies — which are medications that pinpoint and damage cells without affecting most normal and healthy cells — have staked their claim as the standard of care across several patient populations with newly diagnosed CLL.

“Fortunately, in 2022, for patients, regardless of age, comorbidity or risk, it’s an equal playing field in terms of options that are available to our patients,” Dr. Anthony Mato, director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York, said during a presentation at the 26th Annual International Congress on Hematologic Malignancies.

During his presentation, Mato discussed several clinical trials and highlighted an array of data that detailed the safety and efficacy of various targeted therapies.

RESONATE-2 Trial

Mato reviewed data from the RESONATE-2 clinical trial, which led to a Food and Drug Administration approval of Imbruvica (ibrutinib) in 2016.

Here, Mato highlighted findings from a seven-year follow-up of the trial which showed that of the 136 patients who received study drug, 47% continued to receive treatment. Moreover, the average duration of Imbruvica treatment was 6.2 years.

ECOG 1912

Mato also analyzed results from the ECOG 1912 trial. Here, study authors reviewed the safety and efficacy of administering Imbruvica plus another targeted therapy Rituxan (rituximab) versus fludarabine and cyclophosphamide — two chemotherapy agents — with Rituxan.

The study, which was presented in 2019, demonstrated that at a median follow-up of 48 months, treatment with Imbruvica plus Rituxan induced in a three-year progression-free survival rate (percentage of patients living with the disease without the disease worsening) of 89% compared with 71% in the group that received the chemotherapy-based triplet regimen.

Although Mato stressed that chemoimmunotherapy doesn’t have much of a place in treating CLL, he noted a subgroup of patients with IGHV-mutated disease derived a benefit from chemoimmunotherapy that warrants continued use.

CLL14 Trial

Another study Mato explained was the results of a four-year follow-up of the phase 3 CLL14 study. In this trial, where patients received either Gazyva (obinutuzumab) plus Venclexta (venetoclax) or the chemotherapy drug chlorambucil plus Gazyva.

At the time of follow-up, a median progression-free survival had not yet been reached in patients who received Venclexta and Gazyva compared with 36.4 months in the group that received the chemotherapy-based doublet therapy.

Moreover, the four-year progression-free survival rate was significantly higher in the group that received Venclexta and Gazyva (74% versus 35.4%).

Moving Forward

In the end, Mato reviewed several studies highlighting the various efficacy and safety endpoints associated with countless targeted therapies including Gazyva, Venetoclax, Imbruvica and Calquence (acalabrutinib).

Ultimately, he concluded to the audience, that regardless of a patients age or even if they’re considered fit or unfit, that targeted therapies should be the gold standard in the first-line treatment of patients with CLL.

“For patients who are younger than age 65, targeted therapies are the standard of care,” he said. “Although one could still consider chemoimmunotherapy for older fit patients, still targeted therapies are a standard of care. And for less fit patients, targeted therapies are the standard of care.”

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