Medical Policy: 08.01.35 

Original Effective Date: April 2021 

Reviewed: April 2021 

Revised:  

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Multiple myeloma is a hematologic malignancy characterized by abnormal growth of plasma cells with production of abnormal proteins instead of typical antibodies. Plasma cell proliferation in the marrow causes bone pain and fractures due to lytic lesions and displaces other marrow cellular elements. Increase in total or monoclonal proteins can have direct toxic effects on the kidney, resulting in worsening renal function, hypercalcemia and anemia. Treatment of multiple myeloma includes immunomodulatory agents (thalidomide, lenalidomide or pomalidomide), proteasome inhibitors (bortezomib, carfilzomib or ixazomib) and anti-CD38 monoclonal antibodies (daratumumab or isatuximab). While multiple combinations of these agents can lead to remission, most patients eventually relapse.

 

The American Cancer Society estimates for 2021 that 34,290 new cases will be diagnosed, and 14,410 deaths are expected to occur. 

 

On March 26, 2021, the Food and Drug Administration approved idecabtagene vicleucel (Abecma), Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Abecma (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA) directed genetically modified autologous T cell immunotherapy. This is the first FDA-approved cell-based gene therapy for multiple myeloma. 

 

The efficacy of Abecma (idecabtagene vicleucel) (also known as ide-cel) was evaluated in KarMMa (NCT03361748), an open-label, single-arm, multicenter study in adult patients with relapsed and refractory multiple myeloma who had received at least 3 prior lines of antimyeloma therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The study included patients with ECOG performance status of 0 or 1. The study excluded patients with a creatinine clearance of less than or equal to 45 mL/minute, alanine aminotransferase >2.5 times upper limit of normal and left ventricular ejection fraction <45%. Patients were also excluded if absolute neutrophil count <1000 cells/mm3 and platelet count <50,000/mm3. Patients had measurable disease by International Myeloma Working Group (IMWG) 2016 criteria at enrollment. Bridging therapy with alkylating agents, corticosteroids, immunomodulatory agents, proteasome inhibitors, and/or anti-CD38 monoclonal antibodies to which patients were previously exposed was permitted for disease control between apheresis and until 14 days before the start of lymphodepleting chemotherapy. Of 140 patients enrolled, 128 received Abecma (idecabtagene vicleucel). At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD) negative status (<105 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR- T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion. Results of the KarMMa study support Abecma (idecabtagene vicleucel) induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD negative status was achieved in 26% of treated patients. 

 

Summary of Evidence

Abecma (idecabtagene vicleucel) is a B-cell maturation antigen (BCMA) directed genetically modified autologous T cell immunotherapy. The Food and Drug Administration (FDA) approved idecabtagene vicleucel (Abecma), (Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This is the first FDA-approved cell-based gene therapy for multiple myeloma. The efficacy of Abecma (idecabtagene vicleucel) was evaluated in KarMMa (NCT03361748), an open-label, single-arm, multicenter study in adult patients with relapsed and refractory multiple myeloma who had received at least 3 prior lines of antimyeloma therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Efficacy was established on the basis of overall response rate (ORR), complete response (CR) rate, and duration of response (DOR), as assessed by the Independent Response committee (IRC) based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. Response durations were longer in patients who achieved a stringent complete response (CR) as compared to patients with a partial response (PR) or very good partial response (VGPR). Of the 28 patients who achieved a stringent CR, it is estimated that 65% (95% CI: 42%, 81%) had a remission lasting at least 12 months. The median duration of response for VGPR patients (n=25) was 11.1 months (95% CI: 8.7, 11.3) and the median duration of response for PR patients (n=19) was 4.0 months (95% CI: 2.7, 7.2). Results of the KarMMa study support Abecma (idecabtagene vicleucel) induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma. The NCCN guideline for Multiple Myeloma version 6.2021  idecabtagene vicleucel was added to therapy for previously treated multiple myeloma other recommended regimens and is indicated for patients who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

Multiple Myeloma Version 6.2021

Therapy for Previously Treated Multiple Myeloma

  • Idecabtagene vicleucel 

 

Footnote: Indicated for patients who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. 

 

Response Criteria for Multiple Myeloma 
  • Clinical Relapse
    • Clinical relapse requires one or more of the following criteria:
      • Direct indicators of increasing disease and/or end organ dysfunction (calcium elevation, renal failure, anemia, lytic bone lesions [CRAB features]) related to the underlying clonal plasma cell proliferative disorder. It is not used in calculation of time to progression or progression-free survival but is listed as something that can be reported optionally or for use in clinical practice;
      • Development of new soft tissue plasmacytomas or bone lesions (osteoporotic features do not constitute progression);
      • Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as of 50% (and ≥ 1cm) increase as measured serially by the SPD of the measurable lesion;
      • Hypercalcemia (> 11 mg/dL);
      • Decrease in hemoglobin of ≥ 2 g/dL not related to therapy or other non-myeloma related conditions;
      • Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma;
      • Hyperviscosity related to serum paraprotein.
  • Relapse from complete response (to be used only if the endpoint is disease-free-survival)
    • Any one or more of the following criteria:
      • Reappearance of serum of urine M-protein by immunofixation or electrophoresis;
      • Development of ≥ 5% clonal plasma cells in the bone marrow;
      • Appearance of any other sign of progression (i.e. new plasmacytoma, lytic bone lesion or hypercalcemia)
  • Relapsed from MRD negative (to be used only if the endpoint is disease-free survival)
    • Any one of more of the following criteria:
      • Loss of MRD negative state (evidence of clonal plasma cells on NGF or NGS, or positive imaging study for recurrence of myeloma);
      • Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
      • Development of  ≥ 5% clonal plasma cells in the bone marrow;
      • Appearance of any other signs of progression (i.e. new plasmacytoma, lytic bone lesion or hypercalcemia)
  • Progressive disease
    • Any of the following criteria:
      • Increase of 25% from the lowest confirmed response value in one or more of the following criteria
        • Serum M-protein (absolute increase must be ≥ 0.5 g/dL);
        • Serum M-protein increase > 1 g/dL, if lowest M component was ≥ 0.5 g/dL);
        • Urine M-protein (absolute increase must be ≥ 200 mg/24h);
    • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL);
    • In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥ 10%);
    • Appearance of new lesion(s), 50% increase from nadir in SPD of  > 1 lesion, or ≥ 50% increase in the longest diameter of a previous lesion > 1 cm in short axis;
    • ≥ 50% increase in circulating plasma cells (minimum of 200 cells per uL) if this is the only measure of disease     

 

Regulatory Status

On March 26, 2021, the Food and Drug Administration approved idecabtagene vicleucel (Abecma), Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This is the first FDA-approved cell-based gene therapy for multiple myeloma. 

 

Idecabtagene vicleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using a patient’s own T-cells, which are collected and genetically modified, and infused back into the patient.  

 

The idecabtagene vicleucel label carries a boxed warning for cytokine release syndrome (CRS), neurologic toxicities, hemophagocytic lymphohistiocytosis/ macrophage activation syndrome, and prolonged cytopenias. The most common side effects of idecabtagene vicleucel include CRS, infections, fatigue, musculoskeletal pain, and hypogammaglobulinemia.

 

Idecabtagene vicleucel is approved with a risk evaluation and mitigation strategy requiring that healthcare facilities that dispense the therapy must be specially certified to recognize and manage CRS and nervous system toxicities. To evaluate long-term safety, the FDA is requiring the manufacturer to conduct a post-marketing observational study involving patients treated with idecabtagene vicleucel.

 

The safety and efficacy of Abecma in patients under 18 years of age have not been established.

 

Prior Approval:

Prior approval is required.

 

Policy:

See Related Medical Policies 

  • 08.01.27 Cellular Immunotherapy for Prostate Cancer – Provenge (Sipuleucel-T)
  • 08.01.29 Yescarta (Axicabtagene Ciloleucel)*
  • 08.01.30 Kymriah (Tisagenlecleucel)*
  • 08.01.33 Tecartus (Brexucabtagene Autoleucel)*
  • 08.01.34 Breyanzi (Lisocabtagene Maraleucel)*

 

Abecma (Idecabtagene Vicleucel) as a one-time, single administration intravenous infusion treatment is considered medically necessary when ALL of the following criteria are met:

  • Individual is 18 years or older; AND
  • Individual has confirmed diagnosis of multiple myeloma by bone marrow evaluation based on medical documentation; AND
  • Individual has relapsed or refractory disease after four or more prior lines of therapy, including an immunomodulatory agent (Thalidomide [Thalomid], Revlimid [Lenalidomide], Pomalidomide [Pomalyst]), a proteasome inhibitor (Velcade [bortezomib], Kyprolis [Carfilzomib], Ixazomib [Ninlaro]) and an anti-CD38 monoclonal antibody (Daratumumab [Darzalex], Elotuzumab [Empliciti], Isatuximab [Sarclisa]); AND
  • Do not have any of the following:
    • Creatinine clearance ≤ 45mL/minute; OR
    • Alanine aminotransferase (SGPT) >2.5 times upper limit of normal; OR  
    • Ejection fraction <45%; OR
    • Neutrophil count <1000 cells/mm3; OR
    • Platelet count <50,000/mm3; OR
    • Active hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive), if viral load is detectable; a history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing); OR
    • Active infection; OR
    • Active inflammatory disorder; OR
    • History or presence of CNS disorders such as epilepsy/seizure disorder, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or pyschosis; OR
    • History of chimeric antigen receptor therapy (CAR-T) or other genetically modified T-cell therapy; AND
  • The individual will receive Abecma (Idecabtagene Vicleucel) at a treatment center that is certified to administer Abecma (Idecabtagene Vicleucel).

 

Abecma (Idecabtagene Vicleucel) is considered investigational for all other indications, including when the above medical necessity criteria are not met as the safety and efficacy has not yet been established in the peer reviewed medical literature for any other indications and the evidence is insufficient to determine the effects on net health outcomes. 

 

Repeat Treatment

Repeat treatment of Abecma (Idecabtagene Vicleucel) for any indication is considered investigational, as the safety and efficacy beyond one dose has not been studied. The evidence is insufficient to determine the effects on net health outcomes.

 

Required Documentation

The patient’s medical records submitted for review should document the above medical necessity criteria is met and should also include the following:

  • Office notes that contain the confirmed diagnosis and clinical features of the diagnosis (including laboratory results confirming the diagnosis), relevant history and physical and prior cancer treatment history.
  • Lab work and diagnostic testing within 7 to 14 days of the approval request to determine the individual has adequate organ and bone marrow function and meets the medical necessity criteria above.  

 

Policy Guidelines 

Abecma (idecabtagene vicleucel) carries a black box warning for cytokine release syndrome (CRS), neurologic toxicities, hemophagocytic lymphohistiocytosis/ macrophage activation syndrome, and prolonged cytopenias. The most common side effects of idecabtagene vicleucel include CRS, infections, fatigue, musculoskeletal pain, and hypogammaglobulinemia. It is recommended that severe or life-threatening cytokine release syndrome should be treated with tocilizumab.

 

Abecma (idecabtagene vicleucel) should not be administered to patients with active infection or inflammatory disorders.

 

Because of the risk of CRS and neurologic toxicities, Abecma (idecabtagene vicleucel)  is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Abecma REMS. The requirement for the REMS components of the Abecma REMS are the following:

  • Health care facilities that dispense and administer Abecma must be enrolled and comply with the REMS requirements.
  • Certified health care facilities must have onsite, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for administration within 2 hours after Abecma, if needed for treatment of cytokine release syndrome (CRS).
  • Certified health care facilities must ensure that health care providers who prescribe, dispense, or administer Abecma are trained about the management of cytokine release syndrome (CRS) and neurologic toxicities.

 

Refractory Myeloma

  • Primary refractory myeloma is defined as disease that is non-responsive; patients who have never received MR or better with any therapy; and double-refractory multiple myeloma (MM) refers to disease refractory to both proteasome inhibitors and immunomodulatory drugs. 

 

Relapsed Myeloma

  • Reappearance of signs and symptoms of multiple myeloma (MM) after a period of improvement. 

Response Criteria for Multiple Myeloma

  • Clinical Relapse
    • Clinical relapse requires one or more of the following criteria:
      • Direct indicators of increasing disease and/or end organ dysfunction (calcium elevation, renal failure, anemia, lytic bone lesions [CRAB features]) related to the underlying clonal plasma cell proliferative disorder. It is not used in calculation of time to progression or progression-free survival but is listed as something that can be reported optionally or for use in clinical practice;
      • Development of new soft tissue plasmacytomas or bone lesions (osteoporotic features do not constitute progression);
      • Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as of 50% (and ≥ 1cm) increase as measured serially by the SPD of the measurable lesion;
      • Hypercalcemia (> 11 mg/dL);
      • Decrease in hemoglobin of ≥ 2 g/dL not related to therapy or other non-myeloma related conditions;
      • Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma;
      • Hyperviscosity related to serum paraprotein. 
  • Relapse from complete response (to be used only if the endpoint is disease-free-survival)
    • Any one or more of the following criteria:
      • Reappearance of serum of urine M-protein by immunofixation or electrophoresis;
      • Development of ≥ 5% clonal plasma cells in the bone marrow;
      • Appearance of any other sign of progression (i.e., new plasmacytoma, lytic bone lesion or hypercalcemia)
  • Relapsed from MRD negative (to be used only if the endpoint is disease-free survival)
    • Any one of more of the following criteria:
      • Loss of MRD negative state (evidence of clonal plasma cells on NGF or NGS, or positive imaging study for recurrence of myeloma);
      • Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
      • Development of ≥ 5% clonal plasma cells in the bone marrow;
      • Appearance of any other signs of progression (i.e., new plasmacytoma, lytic bone lesion or hypercalcemia)
  • Progressive disease
    • Any of the following criteria:
      • Increase of 25% from the lowest confirmed response value in one or more of the following criteria
        • Serum M-protein (absolute increase must be ≥ 0.5 g/dL);
        • Serum M-protein increase > 1 g/dL, if lowest M component was ≥ 0.5 g/dL);
        • Urine M-protein (absolute increase must be ≥ 200 mg/24h);
    • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL);
    • In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥ 10%);
    • Appearance of new lesion(s), 50% increase from nadir in SPD of  > 1 lesion, or ≥ 50% increase in the longest diameter of a previous lesion > 1 cm in short axis;
    • ≥ 50% increase in circulating plasma cells (minimum of 200 cells per uL) if this is the only measure of disease      

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD diagnosis codes.

  • 0537T Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day
  • 0538T Chimeric antigen receptor T-cell (CAR-T) therapy; preparation of blood-derived T lymphocytes for transportation (eg, cryopreservation, storage)
  • 0539T Chimeric antigen receptor T-cell (CAR-T) therapy; receipt and preparation of CAR-T cells for administration
  • 0540T Chimeric antigen receptor T-cell (CAR-T) therapy; CAR-T cell administration, autologous
  • Revenue Code 0891 Special Process Drugs – FDA Approved Cell Therapy
  • C9399 Unclassified drugs or biologics (When utilized for Abecma [Idecabtagene Vicleucel])
  • J3490 Unclassified drugs (When utilized for Abecma [Idecabtagene Vicleucel])
  • J3590 Unclassified biologics (When utilized for Abecma [Idecabtagene Vicleucel])
  • J9999 Not otherwise classified, antineoplastic drugs (When utilized for Abecma [Idecabtagene Vicleucel])

 

Selected References:

  • Food and Drug Administration (FDA) Drug approvals. FDA approval idecabtagene-vileucel for multiple myeloma
  • Munshi N, Anderson L, Shah M, et.al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med 2021; 384; 705-716
  • National Comprehensive Network (NCCN) Multiple Myeloma Version 5.2021.
  • FDA Labeling Package Insert Abecma (Idecabtagene -Vicleucel)
  • KarMMA Clinical Trail NCT03361748

 

Policy History:

  • April 2021 - New Policy Created

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

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