Multiple Myeloma
Research on multiple myeloma, a plasma cell cancer. Includes proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and CAR-T therapies for relapsed/refractory disease.
Quick Answer
What it is
Research on multiple myeloma, a plasma cell cancer. Includes proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and CAR-T therapies for relapsed/refractory disease.
Key findings
- Grade A: Stem Cell Collection Target (Primary) (Motixafortide (Aphexda))
- Grade A: CD34+ Cell Yield (Motixafortide (Aphexda))
- Grade A: Safety and Tolerability (Motixafortide (Aphexda))
Safety
- Higher risk than bortezomib.
- Consider in patients with cardiovascular risk factors.
- No increased second malignancy risk.
ℹ️ Quick Facts
Quick Facts: Multiple Myeloma
- Supplements Studied:3
3 supps · 15 outcomes
Detailed Outcomes
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A
Stem Cell Collection Target (Primary)
GENESIS Phase 3 (n=122): 67.5% motixafortide vs 9.5% placebo achieved >=6x10^6 CD34+ cells/kg in 2 apheresis sessions (P<0.0001). By local labs: 92.5% vs 21.4%. Led to FDA approval September 2023.
large↑Improves
A
CD34+ Cell Yield
GENESIS trial: Significantly higher total CD34+ cells mobilized vs placebo. More patients achieved target in first apheresis. Fewer total apheresis sessions required. First new mobilization agent in 15 years.
large↑Improves
A
Safety and Tolerability
GENESIS trial: Most common AEs (>20%) were injection site reactions, flushing, pruritus, back pain. Serious AEs in 5.4%. Manageable safety profile. No increased risks vs standard mobilization.
moderate↑Improves
B
Allogeneic Donor Mobilization
Allogeneic donor study: 92% (22/24) achieved >=2.0x10^6 CD34+ cells/kg in 2 leukapheresis. 100% (11/11) at 1.25 mg/kg dose. Single injection regimen offers convenience vs repeated plerixafor dosing.
large↑Improves
A
Progression-Free Survival (KRd)
ASPIRE (n=792): Median PFS 26.3 months with KRd vs 17.6 months with Rd (HR 0.69, P<0.001). 8.7 month improvement. Deep responders (≥CR) achieved 50.4 months PFS.
large↑Improves
A
Overall Survival
ASPIRE final analysis: OS 48.3 vs 40.4 months (HR 0.79, P=0.0045). 7.9 month survival benefit. ENDEAVOR vs bortezomib also showed OS advantage.
moderate↑Improves
A
PFS vs Bortezomib
ENDEAVOR (n=929): Median PFS 18.7 vs 9.4 months with Kd vs Vd (HR 0.53, P<0.0001). Nearly doubled PFS. Establishes superiority over first-generation proteasome inhibitor.
large↑Improves
A
Cardiac Toxicity
SAFETY CONCERN: Heart failure 4-16%, hypertension 9-27%, arrhythmias, QT prolongation (ROR 4.9). FDA FAERS: 38.6% cardiomyopathy-related, 22.7% cardiac failure. Requires baseline cardiac assessment and monitoring.
moderate↑Worsens
A
Thromboembolism
SAFETY CONCERN: 24% embolic/thrombotic events in FAERS database. DVT prophylaxis recommended. Higher risk than bortezomib. Consider in patients with cardiovascular risk factors.
moderate↓Worsens
A
Response Rate (Relapsed MM)
APEX (n=669): Combined CR+PR rate 38% with bortezomib vs 18% with high-dose dexamethasone (P<0.001). Superior response in relapsed MM after 1-3 prior therapies.
large↑Improves
A
Time to Progression
APEX: Median TTP 6.22 months with bortezomib vs 3.49 months with dexamethasone. Nearly doubled time to progression. VISTA: VMP significantly prolonged TTP vs MP.
moderate↑Improves
A
Overall Survival
APEX: 1-year survival 80% vs 66% (P=0.003). VISTA: Persistent OS benefit with VMP vs MP maintained at extended follow-up. No increased second malignancy risk.
moderate↑Improves
A
Frontline Treatment (Elderly)
VISTA (n=682): VMP superior to MP in transplant-ineligible patients. Higher response rates, longer TTP, improved OS. Established standard of care for elderly MM.
large↑Improves
A
Peripheral Neuropathy
SAFETY CONCERN: Incidence 31-45% in Phase 2/3 trials. Dose-limiting toxicity. Sensory > motor, painful, axonal. Subcutaneous route reduces incidence vs IV. 75-81% reversible with dose modification. Prior neurotoxic therapy increases risk.
large↓Worsens
A
Thrombocytopenia
SAFETY CONCERN: Common adverse event, cyclical pattern following dosing. Grade 3-4 in 26-30%. Generally recovers during rest periods. May require dose adjustments or transfusions.
moderate↓Worsens