I'm a provider

The spontaneous regression of certain cancers, such as renal cell cancer or melanoma, supports the idea that the patient's immune system is sometimes capable of delaying tumor progression and on rare occasions can eliminate the tumor altogether. These observations have lead to research interest in a variety of immunologic therapies designed to stimulate the patient's own immune systems.  The major research challenge in adoptive immunotherapy is to develop immune cells with anti-tumor reactivity in quantities sufficient for transfer to tumor-bearing patients. In current trials, two methods are studied: adoptive cellular therapy (ACT) and antigen-loaded dendritic cell infusions.

ACT is “the administration of a patient’s own (autologous) or donor (allogeneic) anti-tumour lymphocytes following a lymphodepleting preparative regimen.” Protocols vary, but include these common steps:

• lymphocyte harvesting (either from peripheral blood or from tumor biopsy)
• propagation of tumor-specific lymphocytes in vitro using various immune modulators
• selection of lymphocytes with reactivity to tumor antigens with ELISA
• lymphodepletion of the host with immunosuppressive agents
• adoptive transfer (i.e., transfusion) of lymphocytes back into the tumor-bearing host

Dendritic cell-based immunotherapy uses autologous dendritic cells (ADC) to activate a lymphocyte-mediated cytotoxic response against specific antigens in vivo. ADCs harvested from the patient are either pulsed with antigen or transfected with a viral vector bearing a common cancer antigen. The activated ADCs are then transfused back into the patient, where they present antigen to effector lymphocytes (CD4+ T cells, CD8+ T cells, and in some cases, B cells). This initiates a cytotoxic response against the antigen and against any cell expressing the antigen. In cancer immunotherapy, ADCs are pulsed with tumor antigens; effector lymphocytes then mount a cytotoxic response against tumor cells expressing these antigens.

In an attempt to further regulate the host immune system, recent protocols use various cytokines (e.g., IL-7 and IL-15 instead of IL-2) to propagate lymphocytes. Protocols also differ in the extent of host lymphodepletion induced prior to transfusing the lymphocytes to the tumor-bearing host.

Note: Allogeneic stem-cell transplantation following nonmyeloablative conditioning of the recipient (known as reduced-intensity conditioning or RIC) may also be referred to as “adoptive immunotherapy” in the literature. However, RIC stem-cell transplantation relies on a donor-versus-malignancy effect of donor lymphocytes, while the adoptive immunotherapy techniques described in this policy enhance autoimmune effects primarily. The use of RIC in stem-cell transplantation is discussed for specific cancers in individual policies related to stem-cell transplantation.

See Active Specific Immunotherapy with Therapeutic Melanoma Vaccines and  Tumor Vaccines policies (added 7-12-2001)

Other applications of adoptive immunotherapy are considered investigational.

None

Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary. 

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

8/1998: Reviewed by MPAC; expanded investigational indications

2/2001: Active Specific Immunotherapy with Therapeutic Melanoma Vaccines reviewed by MPAC; considered investigational

4/16/2001: Managed Care Requirements deleted

7/12/2001: MPAC statement 2/2001 added and hyperlink to Active Specific Immunotherapy with Therapeutic Melanoma Vaccines

2/7/2002: Investigational definition added

4/18/2002: Type of Service and Place of Service deleted

3/17/2003: Code Reference section updated

10/13/2004: Code Reference section reviewed, no changes

11/7/2005:  Code Reference section updated, ICD9 diagnosis code V58.12 added

8/17/2007: Policy reviewed, no changes

12/19/2008: Policy reviewed, policy statement re-written for clarity

04/23/2010: Policy description and guidelines updated based on new rearch findings. Policy statement unchanged. Deleted outdated references in the Sources section.

01/19/2012: Policy reviewed; no changes.

04/02/2013: Policy reviewed; no changes.

All codes billed for this procedure are considered investigational and not eligible for coverage.

Non-Covered Codes