Thousands of myeloma researchers and clinicians from all over the world gathered in Los Angeles, California at the 19th International Myeloma Society (IMS) annual meeting to present and discuss the latest advances in multiple myeloma clinical research. Today, we learned how researchers use data to better predict which patients with multiple myeloma may have a long-lasting response to therapy and which are more likely to experience an early relapse. We also learned that newly diagnosed patients with high-risk disease experienced deep responses to the four-drug induction regimen of Darzalex-Kyprolis-Revlimid- dexamethasone without unacceptable toxicities prior to autologous stem cell transplant (ASCT).
Minimal residual disease (MRD) is an important topic in the field of multiple myeloma, in large part because we have very active treatment regimens that can bring deep and sustained responses to patients, something that was not possible just several years ago. Measuring MRD refers to counting the number of multiple myeloma cells that remain in a patient after a course of therapy is completed. Achieving MRD negativity (that is, no disease detected after treatment) is associated with a significantly longer time before disease progression (progression-free survival [PFS]) and overall survival; however, to date, there has been limited information about its clinical meaning in patients treated with CAR T-cell therapy.
MRD Negativity After Treatment With Abecma (idecabtagene vicleucel)
In the first presentation, investigators from Spain analyzed MRD at months 1, 3, 6 and 12 after Abecma infusion regardless of clinical response in the KarMMa phase 2 clinical trial, which investigated Abecma at different cell doses in 128 patients with triple-class refractory myeloma. Abecma, manufactured by Bristol-Myers Squibb, was the first CAR-T product to receive FDA approval to treat multiple myeloma. The results showed MRD negative patients had significantly greater median PFS (time before disease progression) than MRD positive patients at 1 month following Abecma treatment (11.5 vs 2 months).
Further studies will be needed to better understand the prognostic implication of different response rates and MRD status in patients treated with CAR T-cell therapy.
High-Risk Patients and MRD Negativity
Cytogenetic abnormalities are widely accepted markers for high risk of poor prognosis in patients with multiple myeloma, such as the presence of gain or amplification of chromosome arm 1q21 (gain/amp[1q21]), deletion of chromosome 1p (del[1p]), deletion of chromosome 17p (del[17p]), translocation of chromosomes 4 and 14 (t[4;14]), translocation of chromosomes 14 and 16 (t[14;16]), and translocation of chromosomes 14 and 20 (t[14;20]). To learn more about chromosomal abnormality terminology please see our recent FAQ blog here. MRD negativity has recently emerged as a surrogate for longer survival, regardless of a patient’s cytogenetic risk. Information from newer clinical trials suggests that extended intensified treatment can help achieve MRD negativity in patients with who may have one or more of these high-risk features, which may lead to improved outcomes.
In the next presentation today, researchers from Italy reviewed data from the FORTE trial to assess the impact of high-risk cytogenetic abnormalities in newly diagnosed patients. The FORTE trial evaluated the use of Kyprolis as a part of an induction and consolidation regimen (following ASCT) and maintenance (combined with Revlimid) for newly diagnosed myeloma patients. They evaluated treatment on its ability to lengthen time until disease progression and 1-year sustained MRD negativity according to patient risk.
The authors showed that MRD-negative patients with amp(1q), high circulating tumor cells levels, or multiple high-risk chromosomal abnormalities were at high risk of becoming MRD positive regardless of their treatment. During the exposure to Kyprolis-Revlimid maintenance, patients were at lower risk of becoming MRD positive compared to Revlimid alone. The findings suggest that patients should know if they have any high-risk features/markers and speak to their provider about treatment implications.
To learn more about MRD, we have several educational resources available:
The next abstract used data from the CoMMpass study to evaluate methods that may help better predict how patients respond to therapy. The MMRF CoMMpass Study was designed to provide researchers with as much information as possible about myeloma, by collecting and studying genomic data from more than a thousand patients over the course of their myeloma journey. Researchers from the United Kingdome used data from the CoMMpass study to validate a mutational signature in which absence of mutations across five genes (MGAM, CCDC168, PDXDC1, ABCC1, S1PR2) was associated with better outcome following Kyprolis, Cytoxan, dexamethasone treatment. When applied to data collected from 154 patients in the CoMMpass study who had received upfront Kyprolis-based therapies, the signature was validated. The authors conclude that this genetic signature can be used by clinicians to predict a patient’s response to Kyprolis.
More details about the MMRF CoMMpass Study can be viewed here.
Newly diagnosed, transplant-eligible multiple myeloma patients with high-risk features—defined by the presence of del17p, t(4;14) and/or t(14;16)—is associated with poor outcome. Data presented today from a phase 2 trial from the Intergroupe Francophone du Myelome (IFM) revealed how adding Darzalex to Kyprolis-Revlimid-dexamethasone as induction and consolidation plus double transplant may benefit newly diagnosed, transplant-eligible high-risk myeloma patients. The results showed:
The findings suggested that Dara-KRD as induction prior ASCT is safe and allows deep responses in transplant-eligible newly diagnosed multiple myeloma patients with high-risk cytogenetic profile.
Be sure to hear what myeloma experts Dr. Suzanne Lentzsch and Dr. Saad Usmani have to say about the day’s presentations here.
Stay tuned for more updates from IMS 2022!
