Every December, the international hematology community comes together to share the latest and greatest in research.  

With an expected 35,000 attendees in San Diego this week, there is no doubt that this year’s 66th American Society of Hematology Annual Meeting & Exposition will not disappoint.  A record-breaking 8,500 abstracts were submitted back in August, and it is incredible that well over 1,000 of them are related to multiple myeloma. It is literally impossible to take it all in during the meeting, and I am so thankful the hybrid format allows for a more careful review of what attendees may have missed in person.

As we prepare for the buffet of myeloma research, let me provide an appetizer with my list of top 10 abstracts  that will be presented. Of course, this is not an exhaustive list, but it will provide you with a sampling of the incredible work being done in the field of myeloma. For each of the abstracts below, I will provide a brief commentary as to its importance to myeloma research and care. 

#1 - Abstract #362 - Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma or for Whom Transplant Is Not Planned As Initial Therapy: Analysis of Minimal Residual Disease in the Cepheus Trial. 

This trial is validating the use of this quadruplet combination (daratumumab, bortezomib, lenalidomide, dexamethasone) in patients not eligible or not opting for a stem cell transplant. Its primary endpoint is MRD negativity, pointing to the importance of depth of response. We will very likely have this formally approved soon for patients not going to transplant.

#2 – Abstract #493 - Phase 2 Study of Teclistamab-Based Induction Regimens in Patients with Transplant-Eligible (TE) Newly Diagnosed Multiple Myeloma (NDMM): Results from the GMMG-HD10/DSMM-XX (MajestTEC-5) Trial 

Bispecific antibodies, including  teclistamab, have transformed the treatment of late relapse in myeloma, but we have limited evidence for its use in frontline therapy.  This trial incorporates teclistamab in first line treatment of patients going to transplant and may pave the way for their earlier use. 

#3 – Abstract #494 - Phase 3 Study of Teclistamab (Tec) in Combination with Lenalidomide (Len) and Tec Alone Versus Len Alone in Newly Diagnosed Multiple Myeloma (NDMM) As Maintenance Therapy Following Autologous Stem Cell Transplantation (ASCT): Safety Run-in (SRI) Results from the Majestec-4/EMN30 Trial 

Lenalidomide is used routinely for maintenance therapy, as we know it prolongs remission and even survival after transplant.  However, we are always looking at ways to prolong the time in remission and have tried various combinations to do so. Using a bispecific antibody in addition to lenalidomide in order to prolong post-transplant remission is a unique approach. 

#4 – Abstract #673 IMWG Frailty Score-Adjusted Therapy Delivery Reduces the Early Mortality Risk in Newly Diagnosed Tne Multiple Myeloma: Results of the UK Myeloma Research Alliance (UK-MRA) Myeloma XIV Fitness Trial

With all of the combinations we now use in myeloma, we gain the benefit of increased mechanisms of action to attack myeloma – but we can also increase side effects.  These side effects are even more pronounced in older patients, and those who are frail or have other medical conditions. This study looks at adjusting therapy based on a frailty score and could serve as a template to maximize combinations and minimize complications.

#5 – Abstract #769 -  Isatuximab, Lenalidomide, Bortezomib and Dexamethasone Induction Therapy for Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma: Final Progression-Free Survival Analysis of Part 1 of an Open-Label, Multicenter, Randomized, Phase 3 Trial (GMMG-HD7)

We recently saw the approval of the quadruplet combination of isatuximab, bortezomib, lenalidomide, dexamethasone in patients not going to transplant.  This study evaluated the same combination in patients going to transplant – we had previously seen the benefit over  VRd alone in depth of response as measured by minimal residual disease (MRD) but now will see the results of the duration of that response in PFS (progression-free survival).

#6 – Abstract #770 –  Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Analyses of Minimal Residual Disease (MRD) Negativity Dynamics in the Phase 3 Imroz Study

As in the prior abstract, this quadruplet combination is very effective in frontline myeloma therapy.  The approval in patients not going to transplant was based on this IMROZ trial – this evaluation of the trial will provide more information about the value of MRD testing in this population of patients. 

#7 – Abstract #772 -Belantamab Mafodotin, Bortezomib, and Dexamethasone Vs Daratumumab, Bortezomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Overall Survival Analysis and Updated Efficacy Outcomes of the Phase 3 Dreamm-7 Trial

Belantamab was the first BCMA-targeted approach approved in myeloma. But based on prior trials, it was mostly removed from the market. Two large clinical trials will almost definitely herald its return in 2025, including this trial that combines it with bortezomib (the other trial combines it with pomalidomide).  We still have to sort out the optimal dosing of this drug (perhaps every 12 weeks?), but it will be an important tool in treating myeloma

#8– Abstract #773 - Phase 3 Randomized Study of Daratumumab Monotherapy Versus Active Monitoring in Patients with High-Risk Smoldering Multiple Myeloma: Primary Results of the Aquila Study

This abstract may well be the most talked about one in myeloma at ASH this year – the first readout of a phase 3 trial of daratumumab vs active monitoring in high-risk smoldering multiple myeloma (HR SMM). It may be too early to immediately change practice, but it adds to the evidence of the importance of early intervention in myeloma.

#9 – Abstract #895 - Pre-Apheresis Prediction of Toxicity and Response in Patients Receiving BCMA-Directed CAR-T for Relapsed/Refractory Multiple Myeloma

CAR T-cell therapy has been an incredible addition to our treatments in myeloma with unprecedented response rates and progression-free survival.  However, most patients still experience certain side effects – being able to predict those side effects is an important aspect of reducing them, and this study is designed to predict toxicities even before T cells are collected. 

#10 – Abstract #1031- Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Preliminary Results from the IMMagine-1 Trial 

Many new immunotherapies in development will be presented this coming week.  I am particularly interested in this one as it is a CAR T-cell therapy that is highly effective and perhaps has less of the side effects that we currently face with CAR T, including the potential neurological effects.  

And this is just the beginning!  Stay tuned for the multiple ways the IMF will provide you with a recap of the ASH annual meeting:

Upcoming IMF Coverage of the 2024 American Society of Hematology Annual Meeting & Exposition:

Visit the website Patient Voices at ASH.

Attend the Facebook LIVE on Monday, December 9.

Register for the IMWG Conference Series: Making Sense of Treatment ASH 2024 on Wednesday, December 18.

Follow Post-ASH videos of key abstracts.

Save the date for Latest Myeloma Updates from ASH 2024: Easy-to-Understand Insights for Patients and Care Partners on January 08, 2025.

Check out the ASH 2024 article in the Myeloma Today Winter Edition.