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MMRF ASH 2022 Blog: ASH Day 3!

The final day of ASH gave us some insights into treatment for high-risk patients:  those who are newly diagnosed with active myeloma and those who have smoldering multiple myeloma (SMM). Additionally, new data were presented on the use of Sarclisa in patients who relapsed early vs. late as well as on the risk of developing second primary malignancies after treatment with Revlimid.

High-Risk Smoldering Myeloma and Active Myeloma

Patients who have high-risk SMM progress much more rapidly to active myeloma than other SMM patients; some SMM patients may never have active disease. The ASCENT study (ABSTRACT 757) is investigating a treatment strategy aimed at reducing the risk of progression in high-risk SMM patients. A four-drug regimen (Darzalex-Kyprolis-Revlimd-dex [Dara-KRd]) is used as induction and consolidation followed by maintenance with Dara-R. Of the 41 patients who completed the scheduled treatment, 38 remain on study with 90% of patients progression-free at three years.

Several trials have looked at different induction and maintenance strategies for multiple myeloma patients considered to have high-risk disease; that is, patients who have genetic abnormalities that result in a faster relapse than patients who don’t have these abnormalities. High-risk MM was defined as the presence of certain cytogenetic abnormalities; these abnormalities differed between studies but in general included 1q amplification, t(4;14), t(14;16), t(14;20), and/or deletion(17p). 

The studies that were conducted included:

In these studies, the time until myeloma progressed in patients was lengthened and was observed with the use of KRd as induction (via retrospective analysis) or extended Dara-VR consolidation (via OPTIMUM) and high MRD negativity rates after consolidation with Isa-KRd (via CONCEPT). 

Second Primary Malignancies 

The Myeloma XI study data (ABSTRACT 754) was conducted to assess the impact of Revlimid on the development of second primary malignancies (SPMs) in both patients who had received high-dose melphalan (chemotherapy) and those who did not. In both groups, some patients received Revlimid both at diagnosis and for maintenance therapy, while others only received Revlimid at diagnosis or for maintenance.

In patients who had a stem cell transplant:

For those patients who did not have a stem cell transplant:

Investigators conclude that double-exposure is associated with higher incidence of SPM and while deaths were lower in the groups treated with Revlimid, clinicians should assess each individual’s risk of an SPM before starting Revlimid and have a plan for rapid intervention if needed.

Sarclisa at Relapse

The IKEMA trial (Sarclisa-Kyprolis-dex [Isa-Kd] vs Kyprolis-dex [Kd]) showed that patients with RRMM (who had received 1-3 prior lines of therapy) benefit from the use of isa-Kd with respect to depth of response and prolonged PFS, regardless of whether the relapse was early or late (ABSTRACT 753).

Thanks for following along with our posts this year! To learn more about these data from ASH please register for our upcoming expert session here.