Al-Ola Abdallah, Board Member at Kansas Society of Clinical Oncology, Associate Professor of Medicine, Assistant Professor at University of Kansas Medical Center, shared a post on X:
“High-Risk Cytogenetic Multiple Myeloma remains one of the toughest therapeutic challenges in MM. We analyzed 205 HRMM patients across 6 U.S. centers over 15 years (2009–2024) to understand real-world practice patterns and outcomes.
HRMM defined by:
- del(17p)
- t(4;14), t(14;16), t(14;20)
- gain/amp(1q), del(1p)
- 60% double-hit
- 7.3% triple-hit
A biologically aggressive cohort.
Frontline therapy evolved:
- Triplets still dominant (81%) – VRd most common
- Quadruplets increased: 3.2% – 20.3% (Era 1 – Era 3)
Reflects shift toward intensified upfront therapy.
Anti-CD38 in frontline = modern era shift
- Era 3: 26.6% received CD38-based regimens – Mostly Dara-VRd
Practice aligning with GRIFFIN/PERSEUS data.
ASCT remains central:
- Overall: 75.1%
- <70 yrs: 83.9%
- ≥70 yrs: 43.2%
Fit older pts achieved:
- ≥VGPR: 94.7%
- CR/sCR: 63.2%
Age alone ≠ transplant exclusion.
Depth of response improves with intensification:
Post-induction:
- ORR 83.9%
- ≥VGPR 56.1%
Post-ASCT:
- ≥VGPR 83.8%
- CR/sCR 50.6%.
The major issue: relapse. Despite ASCT + maintenance:
- 69.4% relapsed
- Median follow-up: 47.5 months
HRMM remains an unmet need.
Maintenance is evolving:
- Lenalidomide declining
- More PI+IMiD & CD38-based maintenance
But…
- 22.4% progressed within 12 months
- Current maintenance strategies are insufficient for HRMM.
Clinical implications:
- Earlier quadruplet induction
- Earlier BCMA-directed therapies (CAR-T / TCEs)
- MRD-adapted strategies
- Risk-adapted maintenance intensification.
Key Limitations (important for interpretation):
Retrospective design – selection bias
- No standardized treatment protocols
- 15-year span – major era effect confounding
- Short follow-up in modern era (Era 3)
- No formal KM survival comparisons.
Additional limitations:
- Heterogeneous FISH panels across centers
- Possible under-detection of some cytogenetics
- No MRD data
- Limited toxicity/dose modification data
- Tertiary-center bias – may overestimate access to ASCT/novel agents.
Bottom line: Even with:
- Triplets/quadruplets
- ASCT
- Maintenance
HRMM still relapses early and frequently. The field must move toward: earlier immune redirection + smarter maintenance strategies.”
Title: High-Risk Cytogenetic Multiple Myeloma Remains a Therapeutic Challenge: A 15-Year Real-World Analysis
Authors: Carmel Awadallah, Anas Zayad, Shebli Atrash, Anita Mazloom, Omar Alkharabsheh, Prerna Mewawalla, Mansi R. Shah, Forat Lutfi, Zahra Mahmoudjafari, Muhammad Umair Mushtaq, Jeries Kort, Alma Habib, Al-Ola Abdallah
Read the Full Article.
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