Leveraging CAR T-Cell Therapy Advancements in R/R Multiple Myeloma

In a recent Training Academy hosted by CancerNetwork®, experts in multiple myeloma discussed the evolving role of chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory disease. The panelists highlighted updated findings from clinical trials, recent FDA approvals, and other developments that could change the multiple myeloma treatment paradigm. Here are their key takeaways from the discussion:

CAR T-Cell Therapy Treatment Options

• B-cell maturation antigen expression is common on the surface of multiple myeloma cells, making it a suitable target for immunotherapy.
  • Idecabtagene vicleucel (ide-cel; Abecma), which the FDA approved in March 2021 for use after 4 or more prior lines of therapy, is suitable as third-line therapy for patients with triple class–exposed disease.¹
  • Ciltacabtagene autoleucel (cilta-cel; Carvykti), which received approval in February 2022 for use after 4 or more prior lines of therapy, can be given as second-line therapy to patients with exposure to immunomodulatory drugs and proteasome inhibitors and whose disease is refractory to lenalidomide (Revlimid).²
• One-time infusions may allow patients to achieve minimal residual disease negativity as soon as 28 days following treatment.
  • Prior data suggest improvements in quality of life with CAR T-cell therapy vs other continuous treatments.

Later-Line CAR T-Cell Therapy Data

• Cilta-cel produced an overall response rate of 97.9%
  (95% CI, 92.7%-99.7%) in the phase 1b/2 CARTITUDE-1 study (NCT03548207).³
• In the phase 2 KarMMa trial (NCT03361748), ide-cel yielded a response in 73% of patients (95% CI, 66%-81%), and 33% had a complete or stringent complete response.⁴
  • Ide-cel may still have benefits in patient subgroups, including those with extramedullary disease or high tumor burden.

Early-Line CAR T-Cell Therapy Approvals

• The FDA approved cilta-cel in April 2024 for patients who have received at least 1 prior line of therapy, based on data from the phase 3 CARTITUDE-4 trial (NCT04181827).⁵
• Ide-cel was approved in April 2024 for patients who have had at least 2 prior lines of therapy, based on findings from the phase 3 KarMMa-3 trial (NCT03651128).⁶
• Data from these trials may support the potential benefit of administering CAR T-cell therapy as early as possible.

Suitable Treatment Strategies

• Shared decision-making with patients may be critical when selecting ide-cel vs cilta-cel.
  • Cilta-cel may be considered for patients based on the higher response rate observed in CARTITUDE-1.
  • Ide-cel may still be suitable for older patients with significant morbidities.
• Delayed neurologic toxicity, such as cranial nerve palsy,
  generally appears to be a reversible treatment class effect.
• CAR T-cell therapy may not be suitable for every patient in the second-line setting.
  • An individualized approach based on patient disease biology may
    be necessary.
  • Sequencing these agents is an ongoing challenge.

References

1. US Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the first anti-BCMA CAR T cell therapy for relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb and bluebird bio, Inc. March 26, 2021. Accessed June 17, 2024. https://bwnews.pr/3w4Fa72
2. US FDA Approves CARVYKTI (ciltacabtagene autoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. February 28, 2022. Accessed June 17, 2024. https://prn.to/3vskiZu
3. Munshi N, Martin T, Usmani SZ, et al. CARTITUDE-1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Hemasphere. 2023;7(suppl):e6102468. doi:10.1097/01.HS9.0000967720.61024.68
4. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850
5. CARVYKTI is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 6, 2024. Accessed June 17, 2024. https://tinyurl.com/mr35ycap
6. US FDA approves Bristol Myers Squibb and 2seventy bio’s Abecma for triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. News release. Bristol Myers Squibb and 2seventy bio, Inc. April 5, 2024. Accessed April 5, 2024. https://shorturl.at/abglC