November 12, 2020

It is that time of year again: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition is rapidly approaching, in a virtual format of course, and abstracts have been released for review. We have seen a pattern at ASH in 2018 and 2019, which now continues in 2020. Many ASH abstracts detail immune and genetic findings (myeloma biology); novel immune therapies dominate the schedule; and we have important updates on key trials whose earlier results have already been reported. This is how you build the future of myeloma care—understand the disease better, introduce or update information on cutting-edge new therapies, and consolidate the current standards of care.

I have grouped my nominees for 2020 Top 10 ASH abstracts into the most significant categories.

Top 10 Abstracts for 2020 Virtual ASH Meeting

        New biology of myeloma

1. Our understanding of myeloma is continuously evolving. Some important new concepts will be presented at ASH 2020. The Spanish team has brought together a group of investigators (the Immunocell study group) to sequentially evaluate patients with smoldering multiple myeloma (SMM). They report results for 150 patients, 18 (12%) of whom developed active myeloma. The new observation is that the likelihood of progression correlated with the number of monoclonal plasma cells present in the peripheral blood (PB). This enhanced the recently published 2/20/20 prognostic and predictive scoring system, which is good news.

    

   The researchers also noted that serial changes in immune cell subsets (in the PB) occurred in a correlated fashion and will enhance our understanding of regulatory biology as myeloma evolves to an active state. The Spanish team has separately reported on the genetic transcriptional profiling of these circulating plasma cells and identified over-expression of two genes (CENPF and LGALS1) as indicators of more aggressive disease.
   Also at ASH, additional abstracts discuss specifically the genomics of plasma cell leukemia; the genetic loss of BCMA expression; and immune heterogeneity.
    
2. In a separate abstract, there is an analysis of why some patients are MRD (minimal residual disease) negative (using NGF in the bone marrow) even though the myeloma protein still persists (as measured by immunofixation) in the blood. Several explanations are offered, but it seems that further research is required to understand if a small population of cells persists but does not contribute to relapse (not dangerously mutated or actively growing).
   
   CAR T-cell therapies
    
3. The results of the CARTITUDE trial are updated. As of May 2020, 97 patients had been treated. The overall response rate remains high at 94.8%, with 55.7% of patients in stringent CR (complete response). A key update with regard to adverse events (AEs) was that 10 patients have died during the study: 8 due to AEs and 2 due to disease progression. I am sure there will be keen interest at the ASH meeting to better understand the AE profile.
    
4. The bb2121 (ide-cel) CAR T-cell trial is also updated. Really, not much new to report. The high response rates, dose dependent benefit (at a dose of 150 x10 to 6th cells or greater) are again emphasized, as well as the overall acceptable benefit-risk profile.

    

   Other CAR T-cell abstracts include those reporting on the therapies bb21217; CT053; and P-BCMA-101.
   
   Bispecific and related therapies
    
5. The results of the teclistamab trial are updated. This anti-BCMA / CD3 bispecific antibody again demonstrates encouraging results. Patients have been treated using both intravenous (IV) and subcutaneous (SQ) routes. A combined 120 patients were evaluable for response assessment, with an ORR (overall survival rate) of 63.8%. The safety profile was acceptable, with low-grade cytokine release syndrome (CRS), infection and neurotoxicity being major concerns.
    
6. The results of a study using a first-in-class GPRC5D / CD3 bispecific antibody called talquetamab are also to be presented at this year’s ASH meeting. This novel bispecific molecule also demonstrated encouraging results in 137 treated patients. The overall response rate (ORR) was 78% for IV dosing and 67% for SQ dosing, and the safety profile was manageable. Further details will be awaited at the time of presentation.
   Other related abstracts include studies of the therapies MED12228; REGN5458; BFCR4350A; and TNB-383B.
   
   Clinical trial updates
    
7. The results of the IFM 2009 trial comparing early versus late autologous stem-cell transplant (ASCT) in the setting of Velcade + Revlimid + dexamethasone (VRd) induction are to be presented. With a median follow-up of 93 months (i.e., almost 8 years), the initial progression-free survival (PFS) remains improved for those initially transplanted (47.3 months versus 35 months), but the overall survival is still no different with or without frontline transplant. The achievement of a negative-MRD status continues to be the major predictor of enhanced outcomes. It is important to note that the ability to perform a delayed ASCT is key to allow patients to potentially benefit from that option in the later relapse setting.
    
8. The GRIFFIN trial (VRd +/- Darzalex + ASCT) will be presented again at ASH this year. After a median follow-up of 26.7 months, the addition of Darzalex continues to contribute to improved outcomes with more and deeper responses. For example, the stringent CR rate was 42.4% versus 32%. Full comparative details will be presented.
    
9. The Forte trial (Kyprolis + Revlimid + dexamethasone, with or without ASCT) will again be presented at ASH 2020. This large trial involving 474 previously untreated patients continues to show added benefit with early ASCT compared to 12 cycles of KRd and KCd + ASCT. Maintenance with KR versus Revlimid alone also improve PFS. There is much interest in comparing this trial to the IFM 2009 trial above (#7) in terms of the role and value of early ASCT, even in the setting of excellent induction therapy with KRd.
    
10. The TOURMALINE -MM4 phase 3 trial is updated to present the impact of MRD information. This study is important because it illustrates that achieving an MRD-negative status with ongoing therapy improves outcomes versus patients with persistent MRD-positive disease. There is, thus, value in periodic monitoring during maintenance.

Well, there you have it—these are the ASH abstracts that I believe are important as we build our way steadily to improved outcomes for myeloma patients everywhere. As always, there are many more interesting and important abstracts that will be presented. I will report back on them after the meeting.

Stay safe during these difficult times with COVID-19!