From the Guidelines
Double-hit and triple-hit multiple myeloma patients have a significantly poorer prognosis compared to standard multiple myeloma, with a median overall survival of approximately 2-3 years and less than 2 years, respectively, and require more aggressive treatment approaches, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies in combination regimens.
Key Considerations
- Double-hit myeloma is characterized by two high-risk cytogenetic abnormalities, such as del(17p), t(4;14), t(14;16), or t(14;20), which are associated with a poorer prognosis 1.
- Triple-hit myeloma, involving three high-risk abnormalities, carries an even worse prognosis, with a median survival often less than 2 years.
- The treatment of double-hit and triple-hit multiple myeloma typically involves a combination of proteasome inhibitors (bortezomib, carfilzomib), immunomodulatory drugs (lenalidomide, pomalidomide), and anti-CD38 antibodies (daratumumab) 1.
Treatment Approach
- Early autologous stem cell transplantation is recommended for eligible patients, followed by maintenance therapy.
- Continuous therapy is often necessary rather than fixed-duration treatment, as the disease biology is more aggressive, with faster proliferation, increased genomic instability, and greater resistance to standard therapies.
- Regular monitoring with more frequent disease assessments is essential for these high-risk patients to detect early relapse or progression.
Important Factors to Consider
- The selection of doublet versus triplet therapy should be individualized, taking into account patient-related, disease-related, and treatment-related factors 1.
- Triplet therapy is generally recommended over doublet therapy due to improved clinical outcomes, but toxicity must be considered when selecting therapy.
- The optimal sequence of therapies is unknown, and most published RCTs are lacking, making it essential to maintain a longer duration of therapy at first relapse 1.
From the Research
Double Hit and Triple Hit Multiple Myeloma Prognosis
- The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma 2.
- Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma 2.
- Double-hit patients have a worse prognosis, with more common relapse, faster disease progression, and shorter survival time compared to non-double-hit patients 3.
- The median progression-free survival (PFS) in double-hit patients was 8.0 months, and the median overall survival (OS) was 10.0 months, which were significantly shorter than those in non-double-hit patients 3.
- Cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients 3.
- The risk of disease progression was 3.160 times higher in double-hit patients than in non-double-hit patients, and the risk of death was 2.966 times higher 3.
- Tandem autologous stem cell transplantation (ASCT) can significantly improve the 2-year PFS and OS of multi-hit MM patients 4.
- Lenalidomide, bortezomib, and dexamethasone (RVD) induction chemotherapy regimen combined with tandem ASCT is an effective treatment modality for multi-hit multiple myeloma 4.
- The addition of elotuzumab to RVD induction and maintenance did not improve patient outcomes in high-risk multiple myeloma 5.
- Continuous proteasome inhibitors and immunomodulatory drug combination maintenance therapy may be beneficial for high-risk multiple myeloma patients 5.