Researchers described a possible link between lenalidomide treatment and development of B-cell acute lymphoblastic leukemia (ALL) in patients with chronic lymphocytic leukemia (CLL) in a study with results published in the journal Blood.

The researchers identified 3 patients with CLL who developed ALL during their participation in the treatment arm of the phase 3 CLLM1 clinical trial ( Identifier: NCT01556776). This placebo-controlled trial examined outcomes using lenalidomide maintenance in patients with high-risk CLL who were in first remission following chemoimmunotherapy.

However, according to the researchers, treatment was discontinued early in the CLLM1 study after the detection of ALL in these 3 patients. These patients represented 5.4% of patients in the treatment arm, and diagnoses were confirmed at 15, 33, and 48 months into maintenance treatment.

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Using specimens obtained from the 3 patients with ALL from the CLLM1 study, the researchers performed sequencing of multiple disease-related genes. One observation was a subclonal BIRC3 mutation occurring in both CLL and ALL populations in 1 patient. Other genetic similarities were also found that, taken together, suggested a common clonal B-cell ancestry within CLL and ALL samples from this patient. The researchers additionally detected an IKZF1 frameshift deletion in the patient, which they explained may be related to lenalidomide activity.

The researchers also performed a retrospective cohort analysis of trials conducted by the German CLL Study Group, covering a total of 1679 patients with CLL who had received chemoimmunotherapy in the frontline setting. The cumulative incidence of ALL identified in the analysis of patients treated through the German CLL Study Group trials was 12.6 cases/100,000 patient-years (95% CI, 0.3-70.1). This was lower than the cumulative incidence of ALL in the lenalidomide arm of the CLLM1 study, which was 1345.5 cases/100,000 patient-years (95% CI, 277.5-3932.2).

“In previous reports, ALL has mostly been described as an unrelated second malignancy in patients with CLL and only recently as a clearly clonally related transformation,” the researchers wrote in their report. They considered this study to represent the first report of a clonally related transformation into BCRABL-positive B-cell ALL from CLL, and they concluded there may be link between lenalidomide use and B-cell ALL risk.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Fürstenau M, Fink AM, Schilhabel A, et al. B-cell acute lymphoblastic leukemia in patients with chronic lymphocytic leukemia treated with lenalidomide. Blood. Published online December 23, 2020. doi:10.1182/blood.2020008609

This article originally appeared on Hematology Advisor