Saturday is the first full day at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, and several good sessions on smoldering multiple myeloma (SMM) were presented. In this blog, I want to focus on three study updates and conclude with some thoughts about participating in trials generally.
First, the final analysis of the Centaurus study on Darzalex (daratumumab) monotherapy in SMM was provided by Ola Landgren, MD. This study began in 2015 and sought to determine if Darzalex could delay progression from SMM to multiple myeloma (MM). The study looked at different dosing schedules to optimize future trials. The findings showed Darzalex’s effectiveness and tolerability in patients with intermediate or high-risk SMM.
Three dosing schedules were evaluated over cycles lasting 8 weeks each. Patients in the longest treatment arm showed the highest completion rate of 95%, indicating good tolerability. The study also included an optional extension phase, where patients and their doctors could decide to continue treatment. The data from this extension phase offered insights into the long-term use of Darzalex in this patient population. Results revealed higher response rates in the longer treatment arms compared to the shorter one. Progression-free survival (PFS) was notably extended in the longer treatment arms. Overall survival rates were promising across all dosing cohorts. Importantly, the safety profile remained consistent throughout the study, with no new safety concerns identified
This comprehensive analysis confirmed the clinical benefits of Darzalex monotherapy in intermediate or high-risk SMM. Nearly half of the patients continued treatment for an additional four years during the optional extension phase. These findings support ongoing and future trials, indicating the potential for delaying disease progression and enhancing treatment outcomes.
The next study from the NIH was presented by Elizabeth Hill, MD, and delved into treating high-risk SMM specifically. The approach involved using the drug combination of Kyprolis (carfilzomib), Revlimid (lenalidomide), and dexamethasone, followed by Revlimid maintenance, with the intention of halting or delaying progression.
What the researchers found was promising. This treatment strategy resulted in sustained improvements in patients’ conditions. Nearly all individuals undergoing this treatment did not progress to full myeloma within a five-year timeframe. An interesting observation emerged: those who showed no signs of disease after the initial treatment phase experienced longer periods without any reoccurrence. This suggests that early and intensive treatment might be particularly beneficial, potentially extending the time before the disease reappears.
Hill noted that despite these positive outcomes, there is still a need for further research to pinpoint precisely which patients would benefit most from early intervention. Developing better tools or models to predict which individuals are more likely to progress would be immensely helpful in guiding such treatment decisions. Nevertheless, the study’s findings strongly advocate for continued investigation into effective treatments for high-risk SMM.
The last study, presented by Omar Nadeen, MD, is the Immuno-PRISM study which focuses on high-risk SMM and is still enrolling patients. This trial is exploring the immune targeting treatment of Tecvayli (teclistamab) to determine if early treatment could offer better outcomes. This study is a platform study, meaning that multiple therapies can be examined, with some therapies evolving as the study progresses. The safety and effectiveness of Tecvayli is being studied, and initial results show promising outcomes: all patients are responding to the treatment, with most achieving complete response and becoming minimal residual disease (MRD) negative (meaning very low or undetectable cancer cells). While early, the treatment appears safer with fewer severe infections compared to other similar therapies. This study suggests that starting immune therapy early might be more effective in treating high-risk SMM, offering hope for a better outcome in the future.
This emerging research into SMM paints an optimistic picture, showcasing promising treatments that could potentially halt or delay the progression of this precursor condition to active myeloma. However, amid this optimism, a crucial challenge persists: the necessity for refined predictive models. Identifying which patients should initiate treatment versus those who can safely undergo active surveillance remains a critical question. Developing more accurate and reliable tools for predicting disease progression is paramount, ensuring that interventions are tailored specifically to those who stand to benefit the most. This blend of hopeful advancements and the pressing need for enhanced risk stratification defines the current landscape of SMM research, signaling a path toward more personalized approaches to SMM management.
If you are someone with SMM and are thinking about entering a clinical trial, know that it is a very personal decision. Some factors to consider include the trial’s purpose, potential benefits, potential risks, the treatment’s promise, and its possible side effects. Have thorough discussions with your healthcare team, and make sure you understand the trial’s protocol, eligibility criteria, and the implications for your care and overall lifestyle. Understand the financial costs and time expectations, including travel. Always prioritize your well-being and gather as much information as possible before deciding. Once you start treatment, whether in a trial or not, you will likely be on and off treatment for the rest of your life, at least at this point in time since a curative treatment does not yet exist.
— Jessie Daw
@Daw6Jessie
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