Luciano Costa, MD, PhD, Forecasts Exciting Abstracts at ASH 2021

Luciano Costa, MD, PhD, associate director for Clinical Research at O’Neal Comprehensive Cancer Center, discussed why he’s excited to see abstracts revolving around minimal residual disease (MRD) and immunotherapy presented at the 2021 American Society of Hematology Annual Meeting.

Transcript:

I have a particular interest in MRD response to therapy, and I have an interest in immunotherapy for myeloma in general. I was really looking forward to and excited to see the MRD results of the Cassiopeia trial [NCT02541383].¹ That trial compares bortezomib (Velcade), thalidomide, and dexamethasone [VTd] with daratumumab [Darzalex; DARA]–VTd induction followed by transplant followed by VTd or DARA-VTd consolidation. There was a secondary randomization for maintenance with daratumumab for 2 years or no maintenance. We learned before that the patients who [received] DARA-VTd did not benefit from maintenance, but they did exquisitely well. Now we’re looking at MRD data. If you look at the patients who got DARA-VTd and achieved MRD negativity, which was a good proportion, about 40%, they are doing incredibly well with a progression-free survival [PFS] rate over 95% with 4 years of follow-up. That’s incredible.

That’s a substantial group of people [who] had the deepest level of response with quadruple therapy [and they] have not received any subsequent therapy and continue to do exquisitely well. That again calls into question the current standard that we have, at least in this country, of giving maintenance therapy for everybody. Why does the path [lead to] limited duration therapy without [considering] the need, the cost, the toxicity of indefinite maintenance, which has been our standard.

I was very curious with the data from Sham Mailankody, MBBS, from Memorial Sloan Kettering Cancer Center, [who] is presenting with, to my knowledge, the first clinical data on a CAR T-cell–directed GPRC5D.² It is a small study, but it showed the visibility, the safety, and activity of the CAR T-cell construct. That’s very exciting [and this therapy] greatly broadens the opportunities for CAR T- cell therapy in myeloma.

I’m also excited to see a mature, long-term follow-up with several bispecifics. We’re going to see updates from talquetamab³, cevostamab [RG6160]⁴, and starting to see combination with the teclistamab⁵, showing those agents continue to provide a very high rates of response over 50%. Now those and some of those responses are very durable. We’re making fast steps toward optimizing those and scheduled to eventually bring bispecific therapies to the clinic.

References

1. Loiseau HA, Sonneveld P, Moreau P, et al. Daratumumab (DARA) with Bortezomib, Thalidomide, and Dexamethasone (VTd) in Transplant-Eligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Analysis of Minimal Residual Disease (MRD) Negativity in Cassiopeia Part 1 and Part 2. Presented at: 63rd American Society of Hematology Annual Conference. December 11-14. Abstract 82. Accessed December 8, 2021. https://bit.ly/31Fjeov

2. Mailankody S, Diamonte C, Fitzgerald L, et al. Phase I First-in-Class Trial of MCARH109, a G Protein Coupled Receptor Class C Group 5 Member D (GPRC5D) Targeted CAR T Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma. Presented at the 2021 American Society of Hematology Annual Conference. December 11-14. Abstract 827. Accessed December 8, 2021. https://bit.ly/3ES1Prf

3. Krishnan A, Minnema M, Berdeja J, et al. Updated Phase 1 Results from MonumenTAL-1: First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma. Presented at the 2021 American Society of Hematology Annual Conference. December 11-14. Abstract 158. Accessed December 9, 2021. https://bit.ly/3lMfwQD

4. Trudel S, Cohen A, Krishnan A, et al. Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study. Presented at the 2021 American Society of Hematology Annual Conference. December 11-14. Abstract 157. Accessed December 9, 2021. https://bit.ly/3dCQKOI

5. Rodriguez-Otero P, Dholaria B, Askari E, et al. Subcutaneous Teclistamab in Combination with Daratumumab for the Treatment of Patients with Relapsed/Refractory Multiple Myeloma: Results from a Phase 1b Multicohort Study. Presented at the 2021 American Society of Hematology Annual Conference. December 11-14. Abstract 1647. Accessed December 9, 2021. https://bit.ly/3dCR7c4