Targeted Therapy Associated With Lower SPM Risk Among Treated Patients With CLL

Doctor delivering bad news to a middle-aged patient

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A new study shows patients who receive treatment for chronic lymphocytic leukemia (CLL) are at a heightened risk of having a secondary primary malignancy (SPM), although the report also suggests newer targeted therapies can mitigate much of the risk.

The report was published in the Journal of Comparative Effectiveness Research.

Previous research has shown that patients with CLL are at a greater risk of an SPM than the general population, noted the study authors. An exact reason for the higher risk is not definitively known, they said, but potential reasons include immunodeficiency related to CLL or to standard treatments for the disease.

Standard treatment has traditionally included chemotherapy and chemoimmunotherapy, but the authors said new targeted treatments have improved patient outcomes and resulted in a greater number of CLL survivors. As the survival rate increases, they said the need to understand the association between CLL and SPMs is becoming even more important.

The authors noted that clinical trials of CLL often exclude patients with SPMs, and the retrospective studies that have looked at links between CLL treatment and SPM risk have not assessed whether type of therapy affects the risk of SPM.

They decided to turn to the Surveillance, Epidemiology, and End Results (SEER) Medicare database to analyze SPM risk among people with CLL who were treated (or not) with a variety of therapies. They sought to identify patients at least 66 years old who had a CLL diagnosis and who had data available for at least 12 months before their diagnosis.

Their search yielded 3053 patients who met the criteria for inclusion in the final analysis. The patients received their diagnosis between 2010 and 2016 and were tracked for at least 36 months. Of the total patient population, 20.3% (620 patients) received treatment and the remaining patients remained untreated at 36 months post diagnosis.

About 1 in 5 patients (20.9%) went on to develop an SPM, but the rate was higher in the treated cohort than in the untreated cohort (26.8% vs 19.4%). Squamous cell carcinoma and acute myeloid leukemia were the most common SPMs. Most of the treated patients who had an SPM developed it after therapy initiation, rather than before.

“A possible explanation for this is that patients who require CLL therapy initiation closer to their diagnosis may have a more aggressive form of the disease,” the investigators wrote. “[T]his may have a consequential impact on the incidence of SPMs due to immunodeficiencies associated with CLL predisposing the patient to an increased risk of other malignancies.”

When the investigators examined the impact of the type of therapy used, they found that 30.6% of patients who received anti-CD20 therapy plus chemotherapy had an SPM compared with 21.9% of patients who received anti-CD20 monotherapy and 20.5% of patients who received targeted oral mono- or combination therapy.

The investigators said these data offer insights that could help guide treatment going forward.

“The current study, alongside previously reported data from trials and real-world studies, suggests that targeted agents may help decrease the rate of development of SPMs in patients with CLL,” they concluded. “Furthermore, adequately monitoring the detection of SPMs and the use of novel therapies could provide better control of the disease and possibly reduce the burden of an SPM diagnosis for patients.”

Reference

Ailawadhi S, Ravelo A, Ng CD, et al. Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA. J Comp Eff Res. 2024;13(2):e230119. doi:10.57264/cer-2023-0119