Lenalidomide increases the risk of developing a second primary malignancy (SPM) in patients with multiple myeloma (MM) but not in those with lymphoma or myelodysplastic syndromes (MDS), a meta-analysis suggests. These findings were published in The Lancet Haematology.

The researchers noted that previous meta-analyses revealed an association between lenalidomide and SPMs in patients with MM, but newer randomized controlled trials (RCTs) of lenalidomide for other indications have not shown an increased risk of SPMs.

The researchers therefore sought to evaluate the association between lenalidomide and SPMs in patients with MM, MDS, and lymphomas, including chronic lymphocytic leukemia. 

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The team conducted a meta-analysis of 38 RCTs encompassing a total of 14,058 patients. The RCTs had a median follow-up of at least 1 year and included both lenalidomide and non-lenalidomide treatment arms. 

The results showed no association between lenalidomide and SPMs across all malignancies (risk ratio [RR], 1.16; 95% CI, 0.96-1.39).

Lenalidomide was associated with a significantly increased risk of SPMs among patients with MM (RR, 1.42; 95% CI, 1.09-1.84) but not among patients with lymphoma (RR, 0.90; 95% CI, 0.76-1.08) or MDS (RR, 0.96; 95% CI, 0.23-3.97). 

In the MM cohort, lenalidomide was associated with a significantly increased risk for solid tumor SPMs (RR, 1.30; 95% CI, 1.06-1.60), but the risk for hematologic SPMs did not reach statistical significance (RR, 1.26; 95% CI, 0.93-1.70). 

The failure to reach significance was “probably heavily affected by the FIRST trial [ClinicalTrials.gov Identifier: NCT00689936] due to its large size (n=1613) and the fact that the non-lenalidomide group of this trial used melphalan, a drug with known association with increased hematological SPM,” the researchers wrote.

The risk for SPMs was significantly elevated for MM patients whether they received a transplant (RR, 1.90; 95% CI, 1.44-2.52) or not (RR, 1.25; 95% CI, 1.04-1.51).

“Based on the current data, lenalidomide-induced SPM seem to occur exclusively in patients with multiple myeloma. Thus, lenalidomide can be used for other indications without the major concern of a therapy-related neoplasm,” the researchers wrote.

“In the multiple myeloma setting, lenalidomide is an effective drug, but patients should be monitored both for hematological and solid tumor SPM. This monitoring includes patients that have not received autologous hematopoietic stem cell transplantation.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Sadeem K, Franz J, Klem ML, et al. Second primary malignancies in patients with haematological cancers treated with lenalidomide: A systematic review and meta-analysis. Lancet Haematol. Published online October 27, 2022. doi:10.1016/S2352-3026(22)00289-7

This article originally appeared on Cancer Therapy Advisor