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Second Primary Malignancies and Lenalidomide Treatment: Is There a Connection?

By: Celeste L. Dixon
Posted: Friday, October 6, 2023

Patients with multiple myeloma exposed to more versus less lenalidomide may be likelier to develop a second primary malignancy, according to research results in eClinical Medicine (open-access journal published by The Lancet). However, the use of lenalidomide is safe and effective after autologous stem cell transplantation as maintenance and as continuous therapy in the non–transplant-eligible setting. John R. Jones, MBChB, MRCP, FRCPath, PhD, MSc, BSc, of Brighton and Sussex Medical School in Brighton, United Kingdom, and colleagues noted that lenalidomide reduced myeloma-related mortality, and mortality rates related to second primary malignancies in this context were low.

Monitoring for the development of secondary primary malignancies—including solid tumors such as colon and breast cancers and non-melanoma skin cancers such as squamous cell and basal cell carcinomas—should be incorporated into clinic review processes, the authors suggested. Non–transplant-eligible patients, especially, “have an innately greater risk of secondary carcinogenesis.”

In the phase III Myeloma XI study, 4,358 patients with newly diagnosed myeloma who began treatment between May 2010 and May 2019 (both transplant-eligible and noneligible) were randomly assigned among induction regimens: thalidomide, lenalidomide, or carfilzomib. Ultimately, of 2,274 randomly assigned patients, 1,368 received lenalidomide maintenance (with or without vorinostat), and 906 underwent observation. Median follow-up after maintenance randomization was approximately 1 year for all patients.

Mortality as a result of progressive myeloma was reduced in patients receiving lenalidomide maintenance versus those in the observation arm: 16.6% versus 22.6% and 32.7% versus 41.5% in transplant-eligible and non–transplant-eligible patients, respectively. Simultaneously, the incidence of second primary malignancies was higher in patients who received lenalidomide at induction and maintenance, compared with those treated once with lenalidomide. Of note, mortality related to second primary malignancies and lenalidomide maintenance was relatively low, at 1.8% and 6.1% in transplant-eligible and non–transplant-eligible patients, respectively, compared with 0.4% and 2.8% in those undergoing observation.

Disclosure: The study authors’ disclosure information can be found at thelancet.com.


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