Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Multiple Relapsed Neuroblastoma
Treatment: Treatment Regimen (ifosfamide, carboplatin, etoposide, dinutuximab, and sargramostim) (Pre-Service)
The insurer denied the Treatment Regimen (ifosfamide, carboplatin, etoposide, dinutuximab, and sargramostim) (Pre-Service)
The denial is upheld.

The patient is a male with multi relapse neuroblastoma.  He was diagnosed and treated on a trial basis, then with Cytoxan + topotecan and carboplatin + etoposide, followed by radiation therapy, and then a clinical trial. Further treatment then included Accutane, rituximab + Cytoxan, then topotecan + vincristine + Cytoxan, then Temodar + irinotecan (CPT11), followed by clinical trials and surgery, then Cytoxan + irinotecan + vincristine, a vaccine trial, an oral beta glucan trial, Cytoxan + topotecan + vincristine again two years ago times one cycle, then irinotecan (CPT11) + Temodar again for one cycle, then granulocyte macrophage colony-stimulating factor (GM-CSF) + humanized 3F8 monoclonal antibody (Hu3F8), and then a vaccine trial. The patient's disease progressed this year and he was placed on carboplatin + ifosfamide + etoposide + dinutuximab + granulocyte macrophage colony-stimulating factor (GM-CSF).

No, the health plan should not cover the proposed treatment with ifosfamide, carboplatin, etoposide, dinutuximab, and sargramostim.

No, the requested treatment with ifosfamide, carboplatin, etoposide, dinutuximab, and sargramostim is not more beneficial than any other standard treatment for the patient's condition.
Dinutuximab is approved by the United States Food and Drug Administration (FDA) and has been evaluated in combination with granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 2 (IL-2), and cis-retinoic acid (isotretinoin) [60,94] for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior initial multimodality therapy.

Dinutuximab is a chimeric antibody that targets disialoganglioside GD2, a tumor-associated antigen uniformly expressed on neuroblastomas. The addition of dinutuximab plus cytokines [granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2)] was found to have benefit over cis-retinoic acid alone for prevention of recurrence in a randomized trial. The immunotherapy approach resulted in superior two-year event free survival (EFS) and overall survival (OS) rates (66 versus 46 percent and 86 versus 75 percent, respectively). Toxicities include serious and potentially life-threatening infusion reactions and severe neuropathic pain. The addition of dinutuximab to chemotherapy in patients with relapsed or refractory disease shows high clinical response rates, including those previously receiving dinutuximab therapy.

In a randomized Children's Oncology Group (COG) trial ANBL1221 of 36 patients with neuroblastoma in first relapse/progression treated with irinotecan and temozolomide, the addition of dinutuximab improved objective responses rates compared to temsirolimus (53 versus 6 percent).

There are no studies of dinutuximab in combination with ifosfamide/carboplatin/etoposide to treat relapsed neuroblastoma.  Therefore, the proposed therapy is of no established benefit.