Welcome to our 2024 recap of the latest research on myeloma treatments reported at the American Society of Hematology (ASH) meeting that kicked off Saturday in San Diego. Highlights from today included:
Let’s dive in!
Autologous stem cell transplantation (ASCT) followed by Revlimid (lenalidomide) maintenance continues to be the standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM). Currently, patients with myeloma typically stop maintenance therapy when their disease progresses, meaning there is no set timeframe to stop treatment. However, researchers are finding that patients with sustained (durable) minimal residual disease (MRD) negativity (that means that no myeloma cells were detected) may be able to safely stop maintenance therapy.
In this abstract, researchers from Greece found that maintenance therapy could be stopped for certain patients might be able to stop taking Revlimid maintenance therapy if they were consistently MRD-negative for 3 years. The study included 194 patients who received induction with proteasome inhibitor-based regimens (ie, regiments with Velcade or Kyprolis) and underwent ASCT.
The researchers conclude that sustained MRD negativity after ASCT and a completion of 3 years of Revlimid maintenance may guide the safe discontinuation of maintenance, but more study in clinical trials is needed.
In an analysis of data collected from the MMRF CoMMpass study, Dr. Shan and researchers at the Albert Einstein College of Medicine showed that those who relapse within 12 months of initial therapy have an overall survival (OS) of less than 24 months, regardless of the presence of high-risk features at diagnosis. Out of the 228 myeloma patients classified as functional high-risk myeloma, 63 did not have high-risk chromosomal features specifically–t(4;14), t(14;16), t(14;20), 1q amplification (amp1q), 17p deletion(del17p), or a p53 mutations. The researchers conclude that future studies are needed to confirm if functional high-risk status could be a useful tool for identifying patients who lack chromosomal changes with poor prognosis.
24-hour urine assessments are a key component of International Myeloma Working Group (IMWG) response criteria for myeloma and are requested in clinical trials even if not routinely used in real-world practice. Recent research has suggested a limited role for 24-hour urine assessment if serum immunofixation or free light chain testing is abnormal. In this abstract, Dr. Banerjee and colleagues at the University of Washington analyzed data from 636 patients in the phase 3 STaMINA trial. Outside of situations such as AL amyloidosis where 24-hour urine assessments remain critical or for patients with urine as their only measurable MM biomarker, our results support the removal of 24-hour urine assessments from future iterations of IMWG response criteria.
While there is no cure, the prognosis for myeloma patients has significantly improved, thanks to advances in treatments over the past 10-20 years. The life expectancy for multiple myeloma patients depends on several factors, including the stage of the disease, genetic factors, age, and overall health. One study followed patients for at least 15 years to look at patient- and disease-related factors that may identify those who have a better chance of living 15 years after their diagnosis.
Findings from one abstract of 323 patients in this study, 40 survived at least 15 years. What factors helped predict long-term survival?
Finally, the first day of ASH revealed some promising results on the use of iberdomide in the treatment of newly diagnosed patients who are not eligible for a transplant and those with intermediate and high-risk smoldering multiple myeloma (SMM), an early stage of myeloma that hasn’t yet caused symptoms but is identified by the presence of a serum monoclonal (M) protein of ≥3 g/dL and/or 10% to 60% clonal bone marrow plasma cells.
Iberdomide is a novel oral cereblon E3 ligase modulator (CELMoD™), which is like but more potent than Revlimid, with a dual function: activate the immune system and directly kill myeloma cells.
The first study, which included 75 patients enrolled in an early phase clinical trial, showed the addition of iberdomide combined with Darzalex (daratumumab) and dexamethasone was very effective, with 30 patients achieving MRD negativity.
The second abstract reported findings from an early phase trial that looked at the use of iberdomide alone or in combination with dexamethasone for the treatment of intermediate- or high-risk SMM). Of the 20 patients examined, Dr. Joseph and colleagues from Emory University found that 79% of those with intermediate- or high-risk SMM responded to iberdomide alone or in combination with dexamethasone. Common side effects included headache, abdominal cramping, dyspepsia, and insomnia.
Further studies will continue to evaluate iberdomide for the treatment of early-stages of disease.
Stay tuned tomorrow for additional updates from trials evaluating treatment of patients with newly diagnosed and relapsed/refractory disease.
