Myeloma experts at the Dana Farber Cancer center discuss how they approach the treatment of young patients with multiple myeloma in an article published online in Blood.
The treatment landscape for multiple myeloma has been transformed by the introduction of novel agents, including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. These have been shown to be more effective and generally better tolerated than conventional chemotherapy, with their introduction into clinical practice leading to improved survival. Furthermore, a better understanding of disease biology, improved diagnostic criteria, and the development of sensitive and specific tools for disease prognostication have contributed to better outcome.
Treatment in young patients with multiple myeloma can now be individualized based on host and disease features with enhanced monitoring of response and use of high-sensitivity techniques for evaluating residual disease. The current standard of care has been significantly enhanced by novel agents with a paradigm shift toward optional or delayed autologous stem cell transplant as a reasonable choice in selected patients. Conversely, extended treatment with induction of remission followed by maintenance strategies is now a standard of care, conferring prolonged disease control with more manageable toxicities in both the short and long term, as well as improved quality of life.
Key takeaways on initial treatment options:
- Younger patients with NDMM, active treatment should be initiated as early as possible, and broadly in accordance with IMWG criteria. New data strongly support the use of triplets in NDMM patients.
- They counsel younger patients with Smoldering Multiple Myeloma (SMM) who are eligible for early intervention to consider participation in clinical trials as part of their overall treatment strategy, together with careful observation and the use of bisphosphonates for bone loss.
- All oral treatment with Ixazomib combined with lenalidomide and dexamethasone has shown remarkable overall response rate in 2 single-arm phase II studies in younger transplant-eligible and older patients, with excellent PFS and OS.
- Data from randomized trials using combinations of PIs and IMIDs also show favorable tolerability.
- Another combination to be considered is cyclophosphamide, bortezomib and dexamethasone (CyBorD), which is highly active in NDMM.
What is the Dana Farber Cancer Center choice of initial treatment in the era of novel agents?
“Patients not eligible or choosing not to be included in a clinical trial are treated with RVD for 6-8 cycles as initial treatment or other combinations (eg, KRD, ixazomib/lenalidomide/dexamethasone, or CyBorD), followed by stem cell collection; ASCT is also considered, with maintenance to follow.”
Does the Dana Farber Cancer Center consider ASCT?
“Although ASCT remains a standard of care in MM, this paradigm has evolved with the advent of newer and less toxic therapies, such that a rigid approach to ASCT upfront use outside of clinical studies is difficult to justify. We recommend participation in clinical trials, but for those who are ineligible or decide not to participate, ASCT as an option remains appropriate. For patients preferring to delay ASCT after induction/remission therapy, they should be encouraged to harvest stem cells as soon as a sustained best response is reached (eg, VGPR or better).
What about the use of consolidation?
“Considering that data from the BMT-CTN 0702 trial are still preliminary and that trials have shown a PFS benefit with consolidation treatment, we offer 2-4 cycles of RVD after ASCT in high-risk patients and for those who do not achieve CR after transplant.”
What is their recommendation on maintenance and continuous therapy?
“Post-ASCT, lenalidomide maintenance is a standard of care and is offered to all patients undergoing ASCT, with dose adjust- ments and schedule change according to tolerability. High-risk patients, especially those carrying 17p deletion, are offered the addition of bortezomib. Patients who are not willing to participate in clinical trials and who chose to delay ASCT, are offered continuous therapy with both lenalidomide and bortezomib. Ideally, maintenance should be administered until disease progression; however, this approach is not always feasible, and dose adjustment as well as schedule changes and discontinuation may be necessary if toxicity emerges.”
In conclusion they recommend:
- Younger patients with NDMM, active treatment should be initiated as early as possible, and broadly in accordance with IMWG criteria.
- Induction treatment should contain an IMID, PI, and steroids
- ASCT can reasonably be kept in reserve for patients who do not wish to initially pursue high-dose therapy, with postinduction continuous therapy using lenalidomide recommended and PIs added as clinically appropriate.
- In patients undergoing ASCT, consolidation therapy after ASCT is favored, followed by maintenance with lenalidomide. The addition of bortezomib to maintenance therapy should be considered in patients with high-risk cytogenetics, with other PIs also considered as clinically indicated.
- Typically, the prognostic risk profile of a patient should be determined using clinical and genetic features.
- In all patients, careful attention to supportive care plays a critical role, not least because it allows the avoidance of early complications that may compromise subsequent therapeutic outcome.
- Several other factors should be considered while planning treatment strategy, such as logistics, out-of-pocket cost, drug availability, social considerations, comorbidities, and patient preference.
Reference: Gandolfi S, Paba Prada C, Richardson PG. How I treat the young patient with multiple myeloma. Blood 2018;132(11):1114-1124.