Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Burkitt lymphoma
Treatment: Revlimid
The insurer denied Revlimid as not medically necessary.
The determination is overturned.

The patient initially presented for care with a history of an irregular gait and bilateral lower extremity pain, fever, low energy and chills. He was initially started on amoxicillin for a possible infection. However, his mother then palpated a "ball" in his stomach, so she brought him to the emergency department (ED). A computed tomography (CT) scan was performed that showed multiple abdominal masses, a pelvic wall mass, and a pathologic fracture to the inferior pubic ramus. A CT scan of the chest also showed a mass in the left chest wall and pleural space. Labs showed a lactate dehydrogenase (LDH) of 1300. He had a biopsy of the left chest wall mass and pathology was consistent with Burkitt lymphoma. He was started on chemotherapy as per the Reduce the burden of oncological therapy (ReBOOT) Group B protocol (his cerebrospinal fluid and bone marrow evaluation were both negative). He had one cycle of reduction therapy with cyclophosphamide, vincristine, prednisone, intrathecal therapy and he had a greater than 20% reduction in his disease. He was then started on induction therapy and had two cycles of rituximab, vincristine, methotrexate, dexamethasone, cyclophosphamide, doxorubicin, and intrathecal therapy and once cycle of consolidation with rituximab, methotrexate, cytarabine (ARA-C), and intrathecal chemotherapy. His imaging showed resolution of his disease, and off therapy imaging after a second cycle of consolidation showed continued remission.
He was found to have a periosteal reaction in the left ischium and a new mass in the obturator internus muscle with regional mass effect and shift of the rectum and lower bladder to the right. This was biopsied and pathology was consistent with recurrence of his disease. He was admitted and started on chemotherapy with rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) which led to a second complete remission, and he was given bridging therapy with obinutuzamab. He received 3 weekly treatments of obinutuzumab, zevelin and was admitted for an autologous stem cell transplant. He had another rapid relapse of his disease and was given one cycle of obinutuzumab, polatuzumab, inotuzumab in conjunction with local radiation therapy without improvement in his disease, so two cycles of high-dose ARA-C, standard ARA-C and polatuzumab were given. He then had a maternal haplo transplant using clofarabine, cytarabine and anti-thymocyte globulin (ATG) conditioning with a 5-day local radiation therapy boost. The second transplant was tolerated well, but imaging showed local recurrence again.
The patient was then started on two cycles of bendamustine, polatuzumab and blinatumomab with donor lymphocyte infusion (DLI) . However, he had significant local progression involving new adductor muscles that were not previously involved. He was given rituxumab  and started on ibrutinib. He was then started on monthly rituximab, every 2 week gemcitabine, oxaliplatin, and nivolumab. Daratumumab was added based on cluster of differentiation (CD) 38 positivity of the tumor. Positron emission tomography (PET) imaging again showed disease progression.
At this time, the provider is recommending a treatment that will maximize the time the patient has with his family and improve his quality of life by slowing the disease progression. The provider has recommended treatment with lenalidomide (Revlimid). The use of Revlimid is under review for medical necessity.

In this situation, the requested health service / treatment of Revlimid 10 mg capsule is medically necessary for this patient.
This patient has multiple relapsed/refractory Burkitt lymphoma that has failed several different types of therapy to include chemotherapy, radiation, and stem cell transplant (both autologous and allogeneic). The patient has received many targeted agents for treatment of his disease and the provider has now recommended treatment with Revlimid. This product was denied previously because it is not considered proven as a treatment for this disease.
However, based on a review per the National Cancer Institute (NCI), "there is no standard treatment option for patients with recurrent or progressive" Burkitt lymphoma. The reported survival rates for this disease at this stage are 10-50%, with the largest series showing a survival rate of 20%. Treatment options typically recommended include R-ICE, high-dose cytarabine and etoposide, allogeneic or autologous transplant, anti-CD20 or anti-CD3 antibodies, and rituximab, vincristine, ifosfamide, carboplatin, and idarubicin  (R-VICI). Chemoresistance is the major concern for achieving a durable remission for those who experience relapse.
The current literature has shown that Revlimid has activity against aggressive mature B-cell lymphoma when used both as a single agent and in combination treatments. This medication, which has activity in lymphoid malignancies occurring daily through immune modulation and antiproliferative effects, has been shown to have efficacy in several types of lymphoma. It has been demonstrated to induce apoptosis in Burkitt lymphoma cells mainly through natural killer (NK) cell activation. Maddocks et al demonstrated a positive effect of combination therapy with obinutuzumab, venetoclax and lenalidomide for relapse or refractory B-cell lymphoma. Melani et al recently published results from a Phase II trial that showed ViPOR (Venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide) led to durable complete responses without maintenance therapy in a group of aggressive B-cell lymphoma patients with limited toxicity.
As per a recent review of lenalidomide (Revlimid) therapy in B-cell lymphoma, it was noted that in phase II trials, lenalidomide "exhibited promising activity in both first-line and relapsed / refractory disease across multiple B-cell NHL subtypes". It has also been proven to be safe in pediatric patients for other types of cancer. The dosing selected for this patient is consistent with the previous pediatric studies.
In this situation, the patient has exhausted all other means of therapy for his disease. He has a likely terminal cancer with no standard treatment options. The provider has selected Revlimid based on the best evidence in the peer-reviewed literature and its likely safe and well tolerated profile. If there were Food and Drug Administration (FDA)-approved or other compendia supported treatments for this situation that had not yet been attempted, then the use of Revlimid might not be appropriate. However, for this patient at this time the provider has selected the best possible therapy.