Idecabtagene Vicleucel (Abecma)

Number: 0992

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

---

Policy

Scope of Policy

This Clinical Policy Bulletin addresses idecabtagene vicleucel (Abecma) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of idecabtagene vicleucel (Abecma) is required of all Aetna participating providers and members in applicable plan designs. For precertification of idecabtagene vicleucel (Abecma), contact National Medical Excellence (NME) at 877-212-8811.

1. Criteria for Initial Approval

   Multiple Myeloma

   Aetna considers idecabtagene vicleucel (Abecma) medically necessary for treatment of relapsed or refractory multiple myeloma in members 18 years of age and older when all of the following criteria are met:
   

   1. The member has received prior treatment with at least two lines of therapy, including at least one drug from each of the following categories:

      1. Immunomodulatory agent; and
      2. Proteasome inhibitor; and
      3. Anti-CD38 monoclonal antibody; and
         
   2. The member has not received a previous treatment course of the requested medication or another chimeric antigen receptor (CAR) T-cell therapy directed at any target
   3. The member has an ECOG performance status of 0 to 2; and
   4. The member has adequate and stable kidney, liver, pulmonary and cardiac function; and
   5. The member has no history or presence of clinically relevant central nervous system (CNS) pathology; and
   6. The member does not have clinically significant active infection; and
   7. The member does not have active graft versus host disease; and
   8. The member does not have an active inflammatory disorder.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   See Dosage and Administration information.

Dosage and Administration

Idecabtagene vicleucel (Abecma) is a cell suspension for autologous and intravenous use only and administered at a certified healthcare facility. A single dose of Abecma contains a cell suspension of 300 to 510 x 10⁶ CAR-positive T cells in one or more infusion bags.

Multiple Myeloma

Abecma is administered as a single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive T cells. The dosage range recommended is 300 to 510 x 10⁶ CAR-positive T cells.

Source: Celgene, 2024

Experimental, Investigational, or Unproven

Aetna considers idecabtagene vicleucel experimental, investigational, or unproven for the treatment of solid tumors.

---

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
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
Other CPT codes related to the CPB:
96413 - 96417	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
Q2055	Idecabtagene vicleucel, up to 460 million autologous b-cell maturation antigen (bcma) directed car-positive t cells, including leukapheresis and dose preparation procedures, per therapeutic dose
ICD-10 codes covered if selection criteria are met:
C90.00 – C90.02	Multiple myeloma
C90.10	Plasma cell leukemia not having achieved remission
ICD10 codes not covered for indications listed in the CPB:
C00.0-C88.9, C90.20 – C90.32, C96.0- D09.9	Malignant solid tumors

---

Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Abecma is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Idecabtagene vicleucel is available as Abecma (Celgene Corporation) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy product made up of a patient’s own T cells that are harvested and genetically modified. Abecma is prepared from the patient’s peripheral blood mononuclear cells (PBMCs), which are obtained from a standard leukapheresis procedure. Abecma is a chimeric antigen receptor (CAR)-positive T cell therapy targeting BCMA, which is exhibited on the surface of normal and malignant plasma cells (Celgene, 2024).

Idecabtagene vicleucel (Abecma) carries the following black box warnings:

• Cytokine release syndrome (CRS), including fatal or life-threatening reactions. In clinical trial, any grade CRS occurred in 84% (107/128) of patients. Grade ≥ 3 CRS occurred in 5% (7/128) of patients (Munshi et al., 2021).
• Neurologic toxicities, including severe or life-threatening. In clinical trial, neurological toxicities (NT) occurred in 18% (23/128) of patients. Grade 3 NT occurred in 3% (4/128) of patients and no NT greater than grade 3 occurred (Munshi et al., 2021).
• Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), including fatal and life-threatening reactions. In clinical trial, HLH/MAS occurred in 4% (5/127) of patients (Celgene, 2024).
• Prolonged cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery. In clinical trial, neutropenia occurred in 91% (117/128) of patients, anemia occurred in 70% (89/128), and thrombocytopenia occurred in 63% (81/128) (Munshi et al., 2021).

Additional warnings and precautions include hypersensitivity reactions, infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and effects on ability to drive and use machines.

Per the prescribing information, the most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) were cytokine release syndrome, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.

Multiple Myeloma

In the U.S., myeloma was responsible for an estimated 1.8% (32,270) of all new cancer cases with an estimated 2.1% (12,830) of all cancer deaths in 2020 (NIH, 2021). Multiple myeloma is a rare type of blood cancer involving an accumulation of abnormal plasma cells in the bone marrow which in turn form tumors in many bones of the body. Additionally, this disease impedes the bone marrow from producing enough healthy blood cells thereby resulting in low blood counts. The disease can manifest as damage to bones and the kidneys as well as a weakening of the immune system. Furthermore, multiple myeloma remains incurable and is characterized by periods of remission and relapse. (Celgene, 2021; FDA, 2021).

On March 26, 2021, the U.S. Food and Drug Administration (FDA) approved Abecma (idecabtagene vicleucel) as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy 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. The FDA granted breakthrough therapy and orphan drug designations for Abecma. The FDA approval was based on the efficacy and safety data from the pivotal Phase II KarMMa trial (Celgene, 2021; FDA, 2021).

Munshi and colleagues (2021) evaluated the efficacy and safety of Abecma in KarMMa, an open-label, single-arm, multicenter study consisting of 128 adult patients with relapsed and refractory multiple myeloma who previously received at least 3 lines of antimyeloma therapy including an immunomodulatory agent, proteasome inhibitor, and an anti-CD38 monoclonal antibody. Patients received idecabtagene vicleucel target doses of 150 to 450 x 10⁶ CAR-positive T cells. Eighty-eight percent of patients received four or more prior lines of therapy. Ninety-five percent of patients were refractory to an anti-CD38 monoclonal antibody, 88% of these patients received four or more prior lines of therapy, and 85% were triple-class refractory (refractory to a proteasome inhibitor [PI], an immunomodulatory drug [IMiD] and an anti-CD38 monoclonal antibody). Efficacy results were based on the primary endpoint of overall response (partial response or better) and a key secondary endpoint of complete response or better (including complete and stringent complete responses). At a median follow-up of 13.3 months, 73% (94/128) of patients had a response, and 33% (42/128) of patients had a complete response or better. Safety results from the study included the occurrence of neutropenia in 91% (117/128) of patients, anemia in 70% (89/128) of patients, and thrombocytopenia in 63% (81/128) of patients. Cytokine release syndrome (CRS) and neurologic toxicities (NT) occurred in 84% (107/128) and 18% (23/128) of patients, respectively.

Shah et al (2022) compared the effectiveness of idecabtagene vicleucel (ide-cel, bb2121) versus conventional care (CC) in patients with triple-class exposed relapsed and refractory multiple myeloma (RRMM).  A matching-adjusted indirect comparison was carried out using individual patient-level data from the single-arm, phase-II, KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) Trial and aggregate-level data from MAMMOTH, the largest independent observational study of CC in heavily pre-treated RRMM patients.  Ide-cel improved overall response rate (ORR; odds ratio [OR]: 5.30; 95 % confidence interval [CI]: 2.96 to 9.51), progression-free survival (PFS]; hazard ratio [HR]: 0.50; 95 % CI: 0.36 to 0.70) and overall survival (OS; HR: 0.37; 95 % CI: 0.25 to 0.56) versus CC.  The authors concluded that these findings suggested ide-cel provided improvements in clinical outcomes relative to CC in this heavily pre-treated RRMM population.

Delforge et al (2022) stated that ide-cel showed deep, durable responses in patients with triple-class exposed RRMM in the KarMMa Trial.  These investigators examined health-related quality of life (HRQoL) among KarMMa patients.  The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item MM module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (72 or less hours before or same day as lympho-depletion), day of ide-cel treatment, and after ide-cel treatment . Mean changes from baseline that exceeded the pre-determined threshold of minimally important difference were deemed clinically meaningful.  The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds.  Time to stable improvement (2 or more consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method.  A total of 126 (98 %) of 128 patients treated with ide-cel were included in the HRQoL analysis.  Pre-treatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population.  Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0).  Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment.  The authors concluded that for triple-class exposed patients with RRMM with a poor prognosis and few therapeutic options, a single ide-cel infusion provided early, sustained, statistically significant, and clinically meaningful improvements in HRQoL.

On April 4, 2024, the U.S. Food and Drug Administration (FDA) approved idecabtagene vicleucel (Abecma) for an expanded indication for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The FDA approval was based on supporting data from the KarMMa-3 study, an international, open-label, phase 3 trial (Bristol Myers Squibb, 2024)

In the KarMMa-3 study, Rodriquez-Otero et al. (2023) evaluated idecabtagene vicleucel (Abecma) in adult participants with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen. A total- of 386 participants were randomized 2:1 to receive either Abecma (n=254) or standard regimens (n=132). The standard regimens included daratumumab, pomalidomide, dexamethasone [DPd], daratumumab, bortezomib, dexamethasone [DVd], ixazomib, lenalidomide, dexamethasone [IRd], carfilzomib, dexamethasone [Kd], or elotuzumab, pomalidomide, dexamethasone [EPd]), chosen by investigator prior to randomization contingent upon the patient’s most recent antimyeloma treatment. The dose range for participants in the Abecma group was 150 x 10⁶ to 450 x 10⁶ CAR-positive T cells. Randomization was stratified by age, number of prior antimyeloma regimens, and presence of high-risk cytogenetics abnormalities. In total, 66% of participants had triple-class-refractory disease, and 95% had daratumumab-refractory disease. At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the Abecma group, as compared with 4.4 months in the standard-regimen group (hazard ratio for disease progression or death, 0.49; 95%confidence interval, 0.38 to 0.64; p<0.001). A response occurred in 71% of the participants in the Abecma group and in 42% of those in the standard-regimen group (p<0.001); a complete response occurred in 39% and 5%, respectively. Data on overall survival were immature. Grade 3 or 4 adverse events occurred in 93% of the participants in the Abecma group and in 75% of those in the standard regimens group. Of the 225 participants who received Abecma, cytokine release syndrome occurred in 88%, with 5% having an event of grade 3 or higher, and neurotoxic effects were identified in 15%t, with 3% having an event of grade 3 or higher. The investigators concluded that Abecma significantly prolonged progression-free survival and improved response in comparison to standard regimens in participants with triple-class-exposed relapsed and refractory multiple myeloma who had received two to four regimens previously. Abecma toxicity was similar with previous reports.

---

References