False-positive pregnancy tests in females of reproductive potential receiving lenalidomide in the United States

Lenalidomide is approved in the United States for various indications, including multiple myeloma (MM), myelodysplastic syndrome associated with a deletion 5q cytogenetic abnormality and relapsed, refractory mantle cell lymphoma [1].

Lenalidomide is approved with a Risk Evaluation and Mitigation Strategy (REMS) as it is an analog of thalidomide, a known human teratogen that causes severe developmental deformities, including phocomelia [1]. A goal of the REVLIMID REMS^® program is to prevent the risk of embryo–fetal exposure to lenalidomide. The key elements of this restricted distribution REMS include the certification and education for prescribers and pharmacists, prescribing/dispensing controls, patient enrollment and active program participation and ongoing program assessment. Details of these programs have been described elsewhere [2,3]. The REMS program requires females of reproductive potential (FRP) to use acceptable forms of contraception and undergo medically supervised pregnancy tests prior to starting treatment with lenalidomide and during treatment every 4 weeks with regular menstrual cycles and every 2 weeks with irregular menstrual cycles. The drug is dispensed only if the pregnancy test is negative. Prescribers are required to report all abnormal or positive pregnancy test results to the REMS sponsor (Celgene Corporation). A positive, inconclusive, indeterminate or borderline pregnancy test requires additional testing that can potentially delay the drug dispense while prescribers await the results, medical review and authorization to dispense the drug.

There are several causes of false-positive β–human chorionic gonadotropin (β-hCG) measurements, such as assay issues, interference by non-β-hCG substances, measurement of pituitary β-hCG-like substances, previous injections of β-hCG and free β-hCG-subunit production [4]. Elevation of β-hCG is not unusual in patients with malignant conditions [5]. Positive pregnancy tests have been reported in a postmenopausal woman due to the production of β-hCG by MM cells [6] and in a nongravid, premenopausal woman also due to β-hCG production by MM [7]. A retrospective review of pregnancy test results among FRP who were enrolled and active (received ≥1 product dispense) in the REVLIMID REMS program over the past 10 years was undertaken to determine the prevalence of false-positive pregnancy tests.

All the pregnancy test results among FRP were retrieved from the Celgene safety database using the Medical Dictionary for Regulatory Activities (MedDRA) High Level Term (HLT) Reproductive hormone analyses covering the period from the approval of lenalidomide on 27 December 2005 through 26 December 2015. The demographics of the FRP and number of drug dispenses were retrieved from the Celgene REVLIMID REMS database. The prevalence of false-positive pregnancy tests among FRP who experienced ≥1 false-positive test was calculated for the 10-year period. The proportion of FRP who experienced false-positive pregnancy tests on >1 drug dispense was also determined.

During the 10-year period, there were 193,828 patients (108,275 males [56%] and 85,553 females [44%]) registered in the U.S. REVLIMID REMS program (Table 1). There were 5768 FRP (classified at the first dispense of lenalidomide) representing 7% of all females and 3% of all patients. The median age of all the FRP was 47 years (range, 11–63 years). Total drug dispenses to all the FRP was 67,934, with a median of 6 drug dispense cycles (range, 1–117 cycles) per FRP. A total of 641 false-positive pregnancy test results were reported in 130 of the 5768 FRP. The median age of these FRP was 47 years (range, 26–58 years). The prevalence of FRP reporting false-positive pregnancy tests was 2% (130/5768). The total number of lenalidomide dispenses for these 130 FRP was 2548 with a median of 15 drug dispense cycles (range, 1–71 cycles) per FRP. There were 67,934 drug dispenses, which is equivalent to the number of pregnancy tests. Prior to the drug dispenses, there were 641/67,934 (1%) false-positive pregnancy test results. False-positive pregnancy tests were resolved prior to any drug dispensed.

Table 1. Overview of enrolled and active patients in the REVLIMID REMS program during the 10-year period (27 December 2005 through 26 December 2015).

Characteristics	Total enrolled and active patients N = 193,828
Males, n (%)	108,275 (56.0)
Females, n (%)	85,553 (44.0)
All FRP, n	5768 (7.0% of females; 3.0% of all patients)
Age, median (range), years	47 (11–63)
Total drug dispenses, n	67,934
Drug dispense cycles per FRP, median (range)	6 (1–117)
FRP with false-positive pregnancy test results, n	130
No. of FRP with single false-positive pregnancy test results	48
No. of FRP with repeat false-positive pregnancy test results	82
Age, median (range), years	47 (26–58)
Total drug dispenses, n	2548
Drug dispense cycles per FRP, median (range)	15 (1–71)
Total false pregnancy test results, n  Median (range)	641 2 (1–47)

FRP: females of reproductive potential; REMS: risk evaluation and mitigation strategy.

In the U.S. REVLIMID REMS program, false-positive pregnancy tests were reported in 130 out of a total of 5768 FRP. In a U.S. study of the thalidomide System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program, false-positive pregnancy tests were reported in 69 out of a total of 6022 FRP [8].

In a REMS setting requiring regular pregnancy testing of FRP, and more so for patients with malignant disease, the prescribing community should be aware that false-positive pregnancy tests should be expected [3].

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1361030.

Additional information

Funding

Celgene Corporation10.13039/100006436This work was supported by Celgene Corporation. The authors received editorial and publishing assistance from Celgene Corporation and MediTech Media, Ltd.