Successful desensitization in a patient with lenalidomide hypersensitivity

Abstract

To the Editor: A 48-year-old woman being treated with lenalidomide for kappa light chain multiple myeloma presented with severe rash associated with urticaria, pruritus, and fever. The patient was initially diagnosed with Stage II breast cancer (ER/PR+ and HER-2neu negative) in 2003 and underwent treatment with lumpectomy followed by four cycles of Adriamycin and Cyclophosphamide followed by two cycles of Paclitaxel and then switched to an additional two cycles of Taxotere because of poor tolerance. This was followed by radiation therapy and hormonal therapy. Two years later she was diagnosed with multiple myeloma. As a result of her negative prior experience with chemotherapy and steroids she refused treatment with either and was therefore initially treated with single agent thalidomide. Thalidomide treatment had to be discontinued due to a similar reaction manifesting with severe rash, urticaria, and pruritus, which was thought to be a Type I (IgE mediated) hypersensitivity reaction. When lowered to 50 mg the patient continued to experience side effects necessitating its permanent discontinuation. She was subsequently treated with bortezomib which had to be discontinued secondary to increasing neuropathy. Lenalidomide treatment at the standard dose of 25 mg resulted in the reaction described above which was similar to the reaction she developed on thalidomide, which is not surprising given the structural similarities between the two drugs. The patient was subsequently referred to Allergy-Immunology for desensitization in August 2006. The patient was desensitized using the protocol shown in Table I. In brief, lenalidomide was dissolved in normal saline and diluted to concentrations of 0.025, 0.25, and 2.50 mg/ml. She was given gradually increasing strengths to take orally at 15-to 20-min interval. During the desensitization she had her blood pressure, heart rate, temperature, pulse oximetry, and peak flow monitored. She tolerated the escalating doses with no reaction and was subsequently begun on lenalidomide 15 mg daily, and continues to tolerate daily continuous dosing with no evidence of recurrent hypersensitivity. The patient remains asymptomatic in a PR as defined by the International Working Group Uniform Response Criteria, and also remains free from any evidence of recurrent breast cancer. This represents the first case of successful desensitization to lenalidomide that we are aware of. Since this drug has become an integral component of multiple myeloma therapy this represents an important option for patients who otherwise would not be able to tolerate lenalidomide.

Interleukin-10 is increased in successful drug desensitization regardless of the hypersensitivity reaction type

“…A 12-step standard rapid desensitization protocol was used for immediate reactions [2] and prolonged protocols were used for nonimmediate reactions according to the previously described protocols. Tailor made protocols were generated where no related protocols had been published for individual drugs, as shown in Table 1 [13141516171819].…”

Practical Approaches to the Use of Lenalidomide in Multiple Myeloma: A Canadian Consensus

“…Importantly, patients with a past history of a severe rash associated with thalidomide should not receive lenalidomide. Of interest, one case of skin hypersensitivity reaction to lenalidomide with successful desensitization has been reported [ 59 ]. A similar case has been described for thalidomide [ 60 ], further supporting this intervention for those experiencing type I hypersensitivity to lenalidomide.…”

Lenalidomide Desensitization in Systemic Light-Chain Amyloidosis With Multi-Organ Involvement

“…The fact that these pathways are targeted by lenalidomide on keratinocyte growth and survival, the same might be hypothesized for the development of rash in the epidermis [ 16 ]. Type I (IgE mediated) hypersensitivity reaction has been postulated [ 20 ]. The genetic basis of adverse drug reactions has been described to explain the severe type of skin reactions such as Steven-Johnsons to share the HLA-DRB*1501, and HLA-DQB1*0602 in two patients, whereas the milder rash shares the HLADRB1*1502 and HLA DQB1*0601 genetic information in a patient [ 21 ].…”