The Key milestone achieved in the sphere of the multiple myeloma treatment market was the approval of the first cell-based CAR-T cell therapy, ABECMA (Idecabtagene vicleucel/ide-cel) from Bristol-Myers Squibb and Bluebird bio. ABECMA  was given a green signal by the US Food and Drug Administration (FDA) in March 2021, for the treatment of adult patients with Relapsed/Refractory Multiple Myeloma (RRMM) after four or more prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody. BMS and bluebird bio were thrilled to introduce the first CAR T-cell therapy to suitable triple-class exposed individuals with RRMM, presenting the prospect for a durable response. The company also noted ABECMA’s dedication to delivering on the potential of cell treatments for patients with aggressive and advanced blood malignancies with limited effective treatment alternatives.

In KarMMa -2 Cohort 2b (NCT03601078), adult patients with disease progression <18 months post-1L treatment (no ASCT; at least IMiD agent, proteasome inhibitor, and dexamethasone) received one ide-cel infusion of 150–450×106 CAR+ T cells.

• 

  Patients treated with ide-cel had a high overall response rate (ORR) of 93.5% (78.6% – 99.2%), with >71% achieving the primary endpoint of complete response (CR).

• 

  MRD negativity in evaluable patients with ≥CR was 81% at 12 months and 82% at 24 months.

• 

  By Month 3, ≥85% of patients were stable or had clinically meaningful improvement in QoL (quality of life).

• 

  The 12 and 24-month Progression-free survival (PFS) rates were 70% and 63.3% respectively.

• 

  The 12 and 24-month overall survival (OS) rates were 89.9% and 78.9% respectively.

• 

  Safety profile was manageable and consistent with KarMMa-2a and 2c cohorts.

• 

  Grade 3/4 adverse events occurred in 94% of patients, grade 5 adverse events (AEs) in 6% (both myeloma progression). Grade 3/4 neutropenia and thrombocytopenia occurred in 94% and 35% patients, respectively; time to recovery was 1.5 and 2.0 months. Grade 3/4 infections occurred in 6 (19%) patients.

• 

  Cytokine Release Syndrome (CRS) occurred in 84% patients and investigator-identified neurotoxicity (iiNT) in 10% patients; none were grade ≥3.

KOL insights

“It is important to say to patients that you can add this antibody and gain a lot of efficacy and benefits with no negative QOL impact.” – MD, United States

“Although a high proportion of patients had high tumor burden and high-risk cytogenetics, response rates were high,”- MD, MSc, PhD, United States

Conclusion 

It is now possible to take advantage of the CAR T-therapies such as ABECMA and CARVYKTI in early multiple myeloma therapy regimens. The market for both products is expected to grow as a result of the increased number of patients who may now receive these cell treatments thanks to FDA authorization and label expansion. ABECMA and CARVYKTI are in close competition, despite ABECMA being approved first; CARVYKTI is also gaining traction. BMS's ABECMA, which the FDA approved as a third-line treatment, is now one line behind CARVYKTI thanks to the most recent FDA clearance in the second-line. CARVYKTI generated USD 500 million in 2023 in its launch year on the market, while ABECMA achieved sales of USD 472 million in 2023. 

ABECMA’s US revenue of USD 56 million in the fourth quarter of 2023, as reported by BMS, reflects a decline that can be attributed to the competitive landscape of BCMA-targeted therapies. The competition in this space has intensified with the introduction of various BCMA-targeted therapies, which may include bispecific antibodies, antibody-drug conjugates (ADCs), and other emerging CAR-T therapies. This competitive pressure can lead to market share fragmentation and pricing challenges, impacting ABECMA’s sales performance.

Despite these challenges, BMS and 2seventy bio have achieved a significant milestone by securing FDA approval for ABECMA in a third-line treatment setting. In April 2024, the FDA approved ABECMA for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody, based on results from the KarMMa-3 trial. This approval expands the eligible patient population for ABECMA, allowing it to be used earlier in the treatment paradigm after two prior lines of therapy have been tried.

This strategic regulatory achievement could potentially reposition ABECMA in the market by:

• Providing access to a broader patient base who may benefit from CAR-T therapy.

• Allowing for earlier intervention with ABECMA, which could improve patient outcomes and demonstrate the therapy’s value.

• Enhancing the competitive positioning of ABECMA against other BCMA-targeted therapies by offering a CAR-T option in the third-line setting.

The FDA approval also serves as a testament to the efficacy and safety profile of ABECMA, reinforcing its therapeutic potential. With this regulatory endorsement, BMS and 2seventy bio can leverage marketing and educational efforts to increase awareness and adoption of ABECMA among healthcare providers and patients.

In conclusion, while the fourth quarter performance reflects competitive pressure, the FDA approval in the third-line setting presents an opportunity for ABECMA to regain momentum and achieve growth. It will be important for BMS and 2seventy bio to capitalize on this approval through strategic marketing and access initiatives to maximize ABECMA’s potential in the evolving multiple myeloma treatment landscape.