Sequencing Bispecifics and CAR T-Cell Therapy in R/R Multiple Myeloma

In a recent Training Academy segment hosted by CancerNetwork, a panel of experts in multiple myeloma discussed strategies for sequencing novel bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies for patients with relapsed/refractory disease. Here are their key takeaways:

Recent Approvals in Multiple Myeloma

• Some B-cell maturation antigen (BCMA)–targeting CAR T-cell therapies have become indicated for use in earlier lines of treatment.
  • The FDA approved idecabtagene vicleucel (ide-cel; Abecma) in April 2024 for patients with 2 or more prior lines of therapy based on phase 3 KarMMa-3 results (NCT03651128).¹
  • Ciltacabtagene autoleucel (cilta-cel; Carvykti) received approval in April 2024 for those with at least 1 prior line of therapy based on the phase 3 CARTITUDE-4 results (NCT04181827).²
• Bispecific antibodies are also available for treatment.
  • Talquetamab-tgvs (Talvey) received accelerated approval in August 2023 for those with at least 4 prior lines of therapy based on results from the phase 1/2 MonumenTAL-1 trial (NCT03399799).³
  • Teclistamab-cqyv (Tecvayli) received accelerated approval in October 2022 based on results from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098).⁴
  • Elranatamab-bcmm (Elrexfio) earned accelerated approval status in August 2023 based on results from the phase 2 MagnetisMM-3 trial (NCT04649359).⁵

Challenges With Sequencing

• The need for a caregiver and proximity to a CAR T-cell center may impact therapy availability.
• Despite the ever-evolving nature of the field, current data may support high responses with CAR T-cell
  therapy followed by bispecific agents.
  • On the other hand, waiting at least 6 months after initiating bispecific therapy may be ideal before patients undergo apheresis for CAR T-cell therapy.
• The CAR T-cell collection process may fail in patients.
  • Allogeneic transplants may help patients produce enough
    CAR T cells.

Managing Previously Treated Disease

• Reinfusion with ide-cel or cilta-cel may not be feasible due to the formation of antidrug antibodies.
  • However, sequencing one BCMA-targeting therapy after the other may be possible depending on the extent of cross-reactive antibodies and loss of BCMA.
• CAR T-cell therapy following a bispecific agent may be feasible and give patients an improved treatment-free interval, thereby benefiting quality of life.
  • Duration of the prior bispecific therapy is a critical factor to consider during T-cell collection.

Developing Areas in Treatment

• Sequencing treatment in earlier lines to prolong the duration of response remains an area of focus.
• Optimizing CAR T-cell manufacturing to reduce treatment wait times is another potential development.

References

1. U.S. 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; April 5, 2024. Accessed June 18, 2024. https://shorturl.at/abglC
2. Carvykti is the first and only BCMA-targeted treatment approved by the U.S. FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson; April 5, 2024. Accessed June 18, 2024. https://tinyurl.com/mr35ycap
3. U.S. FDA approves Talvey (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. Janssen Pharmaceutical Company of Johnson & Johnsonl; August 10, 2023. Accessed June 18, 2024. https://prn.to/3KwnjyD
4. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. FDA. October 25, 2022. Accessed June 18, 2024. https://bit.ly/3Fgsi4s
5. Pfizer’s Elrexfio receives U.S. FDA accelerated approval for relapsed or refractory multiple myeloma. News release. Pfizer Inc; August 14, 2023. Accessed June 18, 2024. https://bit.ly/3DTCRIY