With the the 66th ASH Annual Meeting & Exposition still fresh in our minds, Dr Rahul Banerjee (Fred Hutch Cancer Center, Seattle, WA, USA) and Dr Samer Al Hadidi (University of Arkansas for Medical Sciences, Little Rock, AR, USA) outline their top key breakthroughs and take-aways from the conference in multiple myeloma.
Dr Rahul Banerjee
Dr Rahul Banerjee
“The 2024 ASH meeting was filled with fascinating updates in the multiple myeloma (MM) field spanning the breadth of plasma cell disorders. In relapsed/refractory MM, the iMMagine-1 trial (Abstract 1031) of anito-cel (a novel BCMA-targeted CAR-T product) presented by Dr Ciara Freeman and colleagues demonstrated that a future without the risk of Parkinsonism following CAR-T therapy in MM may be possible.”
“In newly diagnosed MM, the IFM2017-03 trial (Abstract 774) presented by Dr Salomon Manier and colleagues set a new standard of care for what I like to call #downwithdex: in short, planned dexamethasone discontinuation after 2 cycles in modern induction regimens.”
“In high-risk smoldering myeloma (SMM), the AQUILA study (Abstract 773) presented by Dr Meletios-Athanasios Dimopoulos and colleagues stole the show with an oral presentation and concurrent publication in the New England Journal of Medicine. In brief, intercepting high-risk smoldering myeloma with a time-limited course of daratumumab was shown to improve overall survival. This trial wasn’t a simple ‘daratumumab now versus daratumumab later’ trial; it was a trial of SMM monotherapy now versus MM multidrug induction/transplantation later – and it rose masterfully to the occasion!”
“In 2025, we as a field are hopeful for regulatory approval for daratumumab as an option for high-risk SMM. Two other drug approvals are anxiously awaited this year as well. Firstly, belantamab mafodotin – a BCMA-targeted antibody drug conjugate largely for CAR-T-ineligible patients – will hopefully be reapproved in the US and Europe based on data from the DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) trials. Secondly, the combination of talquetamab/teclistamab as a ‘bispecific antibody cocktail’ in relapsed/refractory MM demonstrated excellent results in the RedirecTT-1 trial (NCT04586426). I would argue that talquetamab/teclistamab rivals CAR-T in terms of efficacy specifically for patients with visceral extramedullary disease, and of course it can be initiated more rapidly and easily.”
“2025 will be an exciting year for myeloma!”
Dr Samer Al Hadidi
Dr Samer Al Hadidi
“ASH 2024 showcased significant advancements in multiple myeloma and related plasma cell disorders, with a strong emphasis on optimizing early treatment strategies, refining risk stratification, and expanding therapeutic options. The ANDROMEDA trial (Abstract 891) confirmed the long-term survival benefit of upfront Daratumumab-VCD over VCD alone in AL amyloidosis, with a 5-year overall survival (OS) of 76% vs. 65% and faster hematologic and organ responses. Smoldering myeloma remained a focal point, with PANGEA-2 (Abstract 1017) introducing a dynamic predictive model for progression risk, while the AQUILA study (Abstract 773) demonstrated no difference in morbid progression between intervention and observation in smoldering multiple myeloma. BCMA-directed therapies continued to make waves, particularly with the DREAMM-7 study (NCT04246047), where an early OS trend favored Belantamab Mafodotin + Bortezomib/Dexamethasone (BVd) over Daratumumab-based regimens, reinforcing the potential of early BCMA-targeted approaches. Meanwhile, genomic insights from whole-genome sequencing revealed lower APOBEC-related mutational activity in multiple myeloma (MM) patients of African ancestry compared to European ancestry, though no major biological differences were noted. Novel treatment strategies also stood out, including the promising early data on Cevostamab (FcRH5-targeting BsAb), CART-ddBCMA (IMMagine-1) (Abstract 1031), and Inobrodib (CCS1477 [Abstract 1023], a bromodomain inhibitor), as well as a refined frail-patient treatment regimen from IFM2017-03 (Abstract 774) that demonstrated a 4-year PFS using Dara-R with minimal steroid exposure.”
“Several landmark trials presented at ASH 2024 provided crucial insights into the evolving treatment landscape. The final OS analysis from ANDROMEDA was a major highlight, confirming the durability of upfront Dara-VCD with a notable 5-year OS advantage and improved hematologic and organ responses compared to VCD alone. Similarly, the DREAMM-7 trial provided an encouraging signal for BCMA-based therapy, showing a hazard ratio (HR) of 0.57 favoring BVd over DVd, though median OS was not yet reached. This data strengthens the argument for integrating BCMA-targeted approaches earlier in the treatment course.”
“Another groundbreaking development came from IMMagine-1, where CART-ddBCMA achieved an impressive 95% ORR, though longer follow-up is required to assess durability and safety, particularly regarding late adverse events. Additionally, the Inobrodib (CCS1477) trial introduced a novel oral bromodomain inhibitor, with early data showing a 75% ORR at optimal dosing, making it an intriguing option for patients progressing after BCMA therapy. Finally, the IFM2017-03 trial provided a crucial advance in the management of frail patients, showing that Dara-R with limited steroid exposure (discontinued after two cycles) achieved a median PFS of 4 years, offering a viable and less toxic alternative for elderly patients.”
“Looking ahead to 2025, several key areas warrant close attention. The DREAMM-7 OS update will be critical in determining whether early BCMA-based strategies should become standard in relapsed/refractory MM, particularly given the promising HR of 0.57 seen in the first interim analysis. Additionally, long-term safety data on CART-ddBCMA from IMMagine-1 will be essential to better understand the durability of response and late-onset toxicities. The evolving approach to smoldering myeloma management will also be an area of focus, as the PANGEA-2 dynamic model may help refine risk stratification, while the AQUILA study’s Dara-based approach will require further analysis to assess its role in delaying progression to active myeloma.”
“Furthermore, time-limited post-ASCT maintenance strategies from trials like Majestec-4/EMN30 (Abstract 494) will be closely monitored to determine whether intensifying maintenance therapy for a fixed duration can enhance efficacy while maintaining safety. Lastly, novel therapeutic targets beyond BCMA, including Inobrodib and other next-generation agents, will be key in addressing resistance mechanisms and expanding treatment options for heavily pretreated patients. These insights from ASH 2024 will undoubtedly shape the therapeutic landscape in 2025, guiding more personalized and effective treatment approaches for multiple myeloma.”
Disclosures: Rahul Banerjee discloses consultancy with Adaptive, BMS, Caribou Biosciences, Genentech, GSK, JNJ/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi and SparkCures. He has received research funding from Abbvie, JNJ, Novartis, Pack Health, Prothena and Sanofi. Samer Al Hadidi discloses consultancy with Pfizer, Janssen and Sanofi, and grant/research support from the International Myeloma Society and Pfizer.
This content has been developed independently by Touch Medical Media for touchHAEMATOLOGY. It is not affiliated with the American Society of Hematology (ASH). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
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