Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Anaplastic large cell lymphoma.
Treatment: Chemotherapy regimen that includes Brentuximab, Daratumumab and Lenalinomide.
The insurer denied chemotherapy regimen that includes Brentuximab, Daratumumab and Lenalinomide.
The determination is overturned.

The patient has anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive. He was treated per the Children's Oncology Group (COG) protocol ANHL1131 Group C1 with induction of Cyclophosphamide, Oncovine, Prednisone, Adriamycin, and Methotrexate (COPADM), consolidation with cytarabine and etoposide  (CyVE), and a 1-time 10-day course of crizotinib targeting the ALK positive cells. He then had maintenance cycles with vincristine, prednisone, high-dose methotrexate, cyclophosphamide, doxorubicin, triple intrathecal therapy, cytarabine, and etoposide. He completed his therapy and an end of therapy evaluation showed a complete response. However, positron emission tomography (PET) imaging 3 months off-therapy showed a relapse of his disease confirmed by biopsy as ALK positive (+) large B cell lymphoma. He was then treated with 3 cycles of the COG protocol ANHL0121 with ICE [ifosfamide, carboplatin, etoposide]  plus crizotinib as per ANHL12P1. He had a mixed to minimal response. He was started on nivolumab and alectinib and repeat PET imaging showed interval progression of his disease with many new fluorine-18 fluorodeoxyglucose (FDG)-avid bone, liver and lung lesions. He was started on treatment with gemcitabine and oxaliplatin, daratumumab and brentuximab. The facility is also planning on adding lenalidomide. The use of brentuximab, daratumumab and lenalidomide combination therapy is under review.

This patient has multiple recurrent / refractory ALCL / large B-cell lymphoma for which the provider has recommended a combination treatment to include brentuximab, daratumumab and lenalidomide. As per the National Cancer Institute (NCI), "there is no standard approach for the treatment of recurrent or refractory anaplastic large cell lymphoma". Some treatment options noted include ICE, vinblastine, brentuximab, crizotinib and other ALK inhibitors, and transplant. This patient has tried or is being offered each of these treatment options except transplant, which is not likely to be effective if the provider cannot get him into remission first.
Brentuximab is the most highly studied of the requested medications in this disease, following phase II study of adolescents and adults where a complete remission was noted in 55-60% of patients and a partial response was noted in 29% of patients. Another study with this medication noted an overall response rate of 53% and a complete response rate of 41%.
While the data regarding daratumumab is not as strong, it has still been associated with overall response rate of about 7% when used alone in large B cell lymphomas, but the product was well tolerated and the use of it is combination is considered to be appropriate in this setting.
Lenalidomide has the. most recent information regarding the use of this product in ALCL, and patients have demonstrated a significant at least partial response to this therapy in many cases when other products have been ineffective. It is noted to have overall response rates as a salvage therapy of 20+% when used alone, and higher when used in combination.
In this case, the patient has a life-threatening cancer that has failed treatment with many other products. The provider has recommended a treatment regimen that is based on sound scientific evidence and the patient's specific tumor tissue. The patient has no other viable treatment options at this time and the hope is that this combination will result in remission that will allow him to proceed with stem cell transplant.
Therefore, based on the clinical information provided for review, and the current peer-reviewed literature, the chemotherapy regimen that includes brentuximab, daratumumab and lenalidomide is likely to be more beneficial than any standard treatment for the insured's life-threatening disease.