Probably the single most frequently asked question I get as a MM cancer coach is if ASCT vs. novel chemotherapy for myeloma is better.
Of course, “better” means different things to different people.
I believe the word better can mean two different things to most people.
- First, better usually means longer overall survival aka OS aka longer life.
- Secondly, better can mean fewer side effects- short, long-term or late stage.
The two Q and A exchanges below are between me and ChatGPT on Friday December 6th, 2024. After scouring the internet for years trying to research the issue of ASCT vs. novel chemotherapy for myeloma, I was finally able to get specific answers to my question (sort of).
What specific clinical trial demonstrates a superior overall survival benefit for autologous stem cell transplant for newly diagnosed myeloma?
The most notable clinical trial demonstrating a superior overall survival (OS) benefit for autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma is the IFM/DFCI 2009 trial (Intergroupe Francophone du Myélome/Dana-Farber Cancer Institute trial). This trial compared early ASCT to standard therapy in newly diagnosed multiple myeloma patients treated with a modern regimen including lenalidomide, bortezomib, and dexamethasone (RVd).
Key Findings:
- Progression-Free Survival (PFS):
- Early ASCT significantly improved PFS compared to delayed ASCT.
- Median PFS was 50 months in the early transplant group versus 36 months in the non-transplant group.
- Overall Survival (OS):
- At the initial report, no significant OS difference was observed between the groups, likely due to the availability of ASCT as a salvage option for patients in the delayed transplant group.
- However, longer follow-up and subgroup analyses in other related studies and meta-analyses indicate an OS trend favoring early ASCT in some patient subsets.
- Depth of Response:
- Early ASCT was associated with higher rates of minimal residual disease (MRD) negativity, which correlates with longer survival outcomes.
Additional Context:
While the IFM/DFCI 2009 trial did not show an immediate OS benefit, other studies, such as the European Myeloma Network (EMN02/HO95) trial, have supported the role of upfront ASCT, particularly when combined with modern induction and maintenance therapies. A meta-analysis of trials also suggests an OS benefit for ASCT in younger, fit patients.
For newly diagnosed multiple myeloma, on average, which therapy risks fewer side effects- novel therapies alone or autologous stem cell transplant?
For newly diagnosed multiple myeloma, the risk of side effects depends on the specific therapies and the patient’s health profile. Here’s an overview comparing novel therapies alone versus autologous stem cell transplant (ASCT):
Novel Therapies Alone
- Description: Typically includes proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide), and monoclonal antibodies (e.g., daratumumab).
- Side Effects:
- Tend to be less severe and more manageable than those of ASCT.
- Common side effects include fatigue, gastrointestinal symptoms (nausea, diarrhea, or constipation), peripheral neuropathy, and hematologic effects (e.g., anemia, thrombocytopenia).
- Long-term use can lead to cumulative toxicities, but these are often modifiable with dose adjustments.
- Advantages: Avoids the intensive nature of ASCT and is generally better tolerated by older or frailer patients.
Autologous Stem Cell Transplant (ASCT)
- Description: High-dose chemotherapy (typically melphalan) followed by reinfusion of the patient’s own stem cells.
- Side Effects:
- Short-term: Severe but transient side effects include nausea, vomiting, diarrhea, mucositis (mouth sores), and high risk of infections due to profound immunosuppression.
- Long-term: Risks include secondary cancers, persistent fatigue, and potential organ damage (e.g., kidney or heart).
- Advantages: Offers deeper and longer-lasting remissions for many patients and is often combined with novel therapies for optimal outcomes.
Comparison
- Side Effect Profile: Novel therapies alone generally carry fewer and less severe side effects compared to ASCT, making them suitable for patients who cannot tolerate the intensity of transplantation.
- Efficacy Consideration: ASCT is more aggressive and often leads to better long-term disease control, especially in younger and healthier patients, but the higher intensity comes with more severe side effects.
Conclusion
For patients who prioritize minimizing side effects or cannot tolerate high-dose chemotherapy, novel therapies alone are likely to pose fewer risks. However, ASCT remains a cornerstone of treatment for eligible patients due to its potential for deeper remissions. The choice should be personalized based on patient age, health, and treatment goals, often guided by the treating oncologist.
Are you a newly diagnosed myeloma patient? What questions do you have about whether or not to have an autologous stem cell transplant?
Email me at David.PeopleBeatingCancer@gmail.com with your questions.
Thank you,
David Emerson
- Myeloma Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
