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BCMA-Directed Therapy in MM
Managed Care Perspectives in the Implementation of BCMA-Directed Therapy in MM

Released: May 10, 2024

Expiration: May 09, 2025

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Key Takeaways
  • In recent years we have seen an expansion of the treatment armamentarium for multiple myeloma, with BCMA-directed therapies gaining a strong foothold in the relapsed/refractory setting.
  • In addition to cost concerns, optimal BCMA-directed therapy selection and sequencing of available agents present ongoing challenges.

BCMA-Directed Therapy in Relapsed/Refractory Multiple Myeloma (R/R MM)
BCMA-directed therapy has significantly transformed the treatment landscape of MM, with bispecific antibody and CAR T-cell therapies currently FDA approved. The BCMA-directed antibody–drug conjugate, belantamab mafodotin, was initially approved in 2020 and subsequently withdrawn in November 2022. However, it is actively being investigated in several DREAMM clinical trials with other anti-myeloma therapies showing synergistic activity.

Both CAR T-cell therapies—ciltacabtagene autoleucel and idecabtagene vicleuel—were initially FDA approved in the fifth-line setting. In April 2024, both indications were expanded to include earlier lines based on the CARTITUDE-4 and KarMMa-3 trials, respectively. Ciltacabtagene autoleucel is indicated after 1 or more prior line of therapy, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and refractory to lenalidomide. Idecabtagene vicleucel is indicated after 2 or more prior lines of therapy, including an IMiD, PI, and CD38 monoclonal antibody (mAb). The shift of CAR T-cell therapies to earlier lines may increase costs, as more patients will be eligible for these treatments compared to use in later lines. Both CAR T-cell products are available through a REMS program due to the risk of cytokine release syndrome (CRS) and neurotoxicity.

Currently, 3 bispecific antibodies are approved for R/R MM, with 2 BCMA-directed therapies (elranatamab and teclistamab) and 1 targeting GPRC5D (talquetamab). All are indicated after 4 or more prior lines of therapy including a PI, IMiD, and CD38 mAb, and like CAR T-cell therapy, all are available through a REMS program due to the risk of CRS and neurotoxicity.  

Cost Associated With CAR T-Cell Therapy
In a cost per responder analysis of lenalidomide-refractory patients who received ciltacabtagene autoleucel or standard of care treatment with DPd or PVd in the CARTITUDE-4 trial, the cost per complete responder over a 25.4-month period was much lower with ciltacabtagene autoleucel compared to standard of care therapy—$981,884 vs $4,776,015—with more patients achieving a complete response with CAR T-cell therapy. This analysis demonstrates that a single dose of CAR T-cell therapy can result in significant cost savings when compared to continual administration of therapy. Even so, CAR T-cell therapy, beyond that of the product alone, remains a significant healthcare cost, with opportunity to shift administration to the outpatient setting. When investigating total costs, additional factors include pre- and peri-infusion–related expenses, post-infusion monitoring, and adverse event management. In addition, given the delay in access to CAR T-cell therapy, the need for bridging therapy may add to cost. Overall, the total cost of CAR T-cell therapy is a concern for payors.

Challenges With CAR T-Cell Therapy in MM
A major challenge with CAR T-cell therapy in MM is access. A survey of MM experts at treatment centers across the US revealed that a median of 20 patients (range: 5-100) per center are waitlisted since the FDA approval of idecabtagene vicleucel. Patients typically spend a median of 6 months (range: 2-8 months) on the waitlist before leukapheresis. This survey was completed before the expanded indication of CAR T-cell therapy to earlier lines of therapy; it is expected that these numbers may increase with more patients now eligible for this treatment. Reduced access to BCMA-directed therapy, including CAR T-cell therapy, has been recorded outside the US as well.

CAR T-Cell Therapy After CAR T-Cell Therapy
A retrospective study that evaluated real-world administration of idecabtagene vicleucel in a BCMA-exposed subset found that 5 patients had received prior CAR T-cell therapy before idecabtagene vicleucel. Alhough a small subgroup, the overall response rate was 100%. Even though CAR T-cell therapy is approved and typically administered as a one-time therapy, it is interesting that in practice, some patients are receiving more than 1 dose and are still seeing a response. Typically, payor policies restrict use of CAR T-cell therapy to 1 dose per lifetime. So, it will be interesting to see whether guidelines and payor policies change in the future as more data become available.

Bispecific Antibodies in R/R MM
As previously mentioned, 3 bispecific antibodies are approved for R/R MM with additional agents in the pipeline. As these are off-the-shelf products, patients may have access to them sooner than CAR T-cell therapy. Key topics within managed care include:

  • Outpatient administration of step-up dosing with teclistamab
  • Therapy selection among currently available bispecific antibody products and whether payors will have preferred agents in the future
  • Recent FDA approval of a reduced dosing frequency of teclistamab in patients with a complete response or better after at least 6 months of therapy
  • Ongoing studies of bispecific antibodies in combination with other therapies

Sequencing Bispecific Antibody and CAR T-Cell Therapy
With the expansion of the immunotherapy options for treatment of R/R MM, the question becomes: how do we best sequence these therapies? At present, there is not a standardized approach, and treatment selection varies based on prior therapy as well as provider and patient-specific factors. Prospective studies on sequencing and therapy selection are currently lacking. Factors including patient comorbidities, therapy access, time to administration, and toxicity must be considered when determining an optimal treatment plan for an individual patient. When considering toxicity profile, it is important to understand that although CRS is a common AE with both CAR T-cell therapy and bispecific antibodies, CAR T-cell therapy is associated with a higher rate and severity of CRS and neurotoxicity, and bispecific antibodies are associated with a higher incidence and severity of infections.

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