Condition
Multiple Myeloma
Multiple myeloma is a cancer of plasma cells, the antibody-making immune cells in bone marrow, which crowd out healthy blood cells. Evidence is strongest for bortezomib and carfilzomib: trials in relapsed disease found bortezomib produced responses in 38% versus 18% on a steroid, and carfilzomib added to standard drugs extended time without progression from 17.6 to 26.3 months. Motixafortide, also strongly studied, was tested for collecting stem cells before transplant instead.
Sources: PMID 15958804; PMID 29341834
- Updated
- How we grade
- 100 studies cited
- Supplements studied
- 0
- Medicines and peptides
- 3
- Graded outcomes
- 15
No supplement studies yetWe haven’t found supplement studies for Multiple Myeloma. The medicines and peptides studied for it are listed below.
Prescription medicines and peptides studied, for context
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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. | Improves (the measure goes up) | Large effect | 16 studies | |||
Studies that measured response rate (relapsed mm) | ||||||
| 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. | Improves (the measure goes up) | Moderate effect | 15 studies | |||
Studies that measured overall survival | ||||||
| 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. | Improves (the measure goes up) | Large effect | 15 studies | |||
Studies that measured frontline treatment (elderly) | ||||||
| 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. | Worsens (the measure goes down) | Large effect | 15 studies | |||
Studies that measured peripheral neuropathy | ||||||
| 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. | Improves (the measure goes up) | Moderate effect | 14 studies | |||
Studies that measured time to progression | ||||||
| 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. | Worsens (the measure goes down) | Moderate effect | 14 studies | |||
Motixafortide (Aphexda)
- Stem Cell Collection Target (Primary): improves
- CD34+ Cell Yield: improves
- Safety and Tolerability: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| 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. | Improves (the measure goes up) | Large effect | 11 studies | |||
Studies that measured stem cell collection target (primary)
| ||||||
| 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. | Improves (the measure goes up) | Large effect | 11 studies | |||
Studies that measured cd34+ cell yield
| ||||||
| 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. | Improves (the measure goes up) | Moderate effect | 5 studies | |||
Studies that measured safety and tolerability | ||||||
| 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. | Improves (the measure goes up) | Large effect | 11 studies | |||
Studies that measured allogeneic donor mobilization
| ||||||
Key findings
- Cardiac ToxicityWorsens (the measure goes up)
- Progression-Free Survival (KRd)Improves (the measure goes up)
- Overall SurvivalImproves (the measure goes up)
Safety notes in the studies
- Higher risk than bortezomib.
- Consider in patients with cardiovascular risk factors.
- No increased second malignancy risk.
Studies cited
100 studies from PubMed
- Cancer targeting carfilzomib nanomedicine: a comprehensive review of delivery vehicles and efficacy.
- Health-Related Quality of Life in Patients With Relapsed/Refractory Multiple Myeloma Treated With Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone: An Analysis of Patient-Reported Outcomes From the Phase 3 CANDOR Trial.
- Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial.
- Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024.
- Bortezomib in cancer therapy: Mechanisms, side effects, and future proteasome inhibitors.
- Doxorubicin synergizes bortezomib-induced multiple myeloma cell death by inhibiting aggresome formation and augmenting endoplasmic reticulum/Golgi stress and apoptosis.
- Carfilzomib suppressed LDHA-mediated metabolic reprogramming by targeting ATF3 in esophageal squamous cell carcinoma.
- Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.
- HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.
- Characteristics and outcomes of patients developing pulmonary hypertension associated with proteasome inhibitors.
- An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study.
- Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.
- Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial.
- Carfilzomib-induced thrombotic microangiopathy (TMA) refractory to eculizumab: A case report and literature review.
- Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review.
- A comparative review of Aphexda and Mozobil for mobilization prior to stem cell collection.
- Bortezomib is efficacious in the treatment of severe childhood-onset neuropsychiatric systemic lupus erythematosus with psychosis: a case series and mini-review of B-cell immunomodulation in antibody-mediated diseases.
- Selinexor-Bortezomib-Dexamethasone: A Review in Previously Treated Multiple Myeloma.
- Carfilzomib-induced life-threatening lung injury in refractory multiple myeloma.
- Lactoferrin ameliorates carfilzomib-induced renal and pulmonary deficits: Insights to the inflammasome NLRP3/NF-κB and PI3K/Akt/GSK-3β/MAPK axes.
- Canagliflozin mitigates carfilzomib-induced endothelial apoptosis via an AMPK-dependent pathway.
- Carfilzomib-induced Thrombotic Microangiopathy: A Case Based Review.
- Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial.
- Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial
- Innovations in hematopoietic stem-cell mobilization: a review of the novel CXCR4 inhibitor motixafortide
- Hematopoietic stem cell mobilization for allogeneic stem cell transplantation by motixafortide, a novel CXCR4 inhibitor
- Bortezomib-resistant multiple myeloma patient-derived xenograft is sensitive to anti-CD47 therapy.
- Treatment with bortezomib for recurrent proliferative glomerulonephritis with monoclonal IgG deposits in kidney allograft. Case report and review of the literature.
- Bortezomib-Induced Ovarian Toxicity in Mice.
- Foot drop in patients treated with bortezomib - a case series and review of the literature.
- Carfilzomib modulates tumor microenvironment to potentiate immune checkpoint therapy for cancer.
- Efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma: A meta-analysis.
- Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews.
- An Untargeted Metabolomics Approach on Carfilzomib-Induced Nephrotoxicity.
- Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group.
- Carfilzomib-induced thrombotic microangiopathy is underestimated in clinical practice: A report of five patients and literature review.
- MSX-122: Is an effective small molecule CXCR4 antagonist in cancer therapy?
- Bortezomib limits renal allograft interstitial fibrosis by inhibiting NF-κB/TNF-α/Akt/mTOR/P70S6K/Smurf2 pathway via IκBα protein stabilization.
- Bortezomib-induced acute pancreatitis, an uncommon adverse event.
- Bortezomib-loaded lipidic-nano drug delivery systems; formulation, therapeutic efficacy, and pharmacokinetics.
- Bortezomib in anti-N-Methyl-d-Aspartate-Receptor (NMDA-R) encephalitis: A systematic review.
- Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR
- Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer.
- Fatal pulmonary toxicity following Carfilzomib administration.
- Incidence and Management of Carfilzomib-induced Cardiovascular Toxicity; A Systematic Review and Meta-analysis.
- Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.
- Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial.
- Hematopoietic stem cell mobilization: a concise review
- Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization
- At the Bedside: Profiling and treating patients with CXCR4-expressing cancers.
- Motixafortide and Pembrolizumab Combined to Nanoliposomal Irinotecan, Fluorouracil, and Folinic Acid in Metastatic Pancreatic Cancer: The COMBAT/KEYNOTE-202 Trial.
- Bortezomib - First Therapeutic Proteasome Inhibitor for Cancer Therapy: A Review of Patent Literature.
- Bortezomib for immune thrombocytopenia and autoimmune hemolytic anemia.
- Bortezomib for autoimmune hemolytic anemia after intestinal transplantation.
- Biotinylated HPMA centered polymeric nanoparticles for Bortezomib delivery.
- Utilization of Lipid-based Nanoparticles to Improve the Therapeutic Benefits of Bortezomib.
- Population-based meta-analysis of bortezomib exposure-response relationships in multiple myeloma patients.
- Bortezomib-based consolidation or maintenance therapy for multiple myeloma: a meta-analysis.
- Carfilzomib-Induced Pulmonary Hypertension.
- Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials.
- Venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory multiple myeloma harboring t(11,14)(q13;q32): two case reports and a review of the literature.
- Infection risk with carfilzomib in multiple myeloma: a systematic review and meta-analysis of randomised controlled trials.
- Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.
- BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial.
- Spotlight on Bortezomib: potential in the treatment of hepatocellular carcinoma.
- The efficacy and safety of bortezomib-based chemotherapy for immunoglobulin light chain amyloidosis: A systematic review and meta-analysis.
- Bortezomib promotes apoptosis of multiple myeloma cells by regulating HSP27.
- Subcutaneous bortezomib might be standard of care for patients with multiple myeloma: a systematic review and meta-analysis.
- Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma.
- Apremilast ameliorates carfilzomib-induced pulmonary inflammation and vascular injuries.
- [Efficacy and Safety of Carfilzomib in the Treatment of Multiple Myeloma：A Systematic Evaluation].
- Carfilzomib: A Tale of a Heartbreaking Moment: Case Report and Concise Review of the Literature.
- The safety of bortezomib for the treatment of multiple myeloma.
- Subcutaneous versus Intravenous Bortezomib Administration for Multiple Myeloma Patients: a Meta-analysis.
- Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
- Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysis
- Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials
- Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials
- Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis.
- Efficacy and toxicity profile of carfilzomib based regimens for treatment of multiple myeloma: A systematic review.
- Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.
- Efficacy and safety of bortezomib, thalidomide, and lenalidomide in multiple myeloma: An overview of systematic reviews with meta-analyses.
- Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis.
- Bortezomib-Induced Muscle Toxicity in Multiple Myeloma.
- Bortezomib could down-regulate the expression of RANKL, inhibit cell proliferation and induce cell apoptosis in the human myeloma cell line RPMI 8226 by activating casepase-3.
- Weekly versus biweekly bortezomib given in patients with indolent non-Hodgkin lymphoma: A meta-analysis.
- Bortezomib-induced syndrome of inappropriate antidiuresis in a patient with multiple myeloma: A case report and literature review .
- Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial
- Proteasome inhibitor-induced gastrointestinal toxicity.
- Carfilzomib/pomalidomide single-agent or in combination with other agents for the management of relapsed/refractory multiple myeloma: a meta-analysis of 37 trials.
- Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials.
- BKT140 and BKT200 - Second-generation peptide CXCR4 antagonists
- Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study
- Management of Carfilzomib-Associated Cardiac Adverse Events
- Fatal pulmonary toxicity due to carfilzomib (Kyprolis™).
- Carfilzomib reverses pulmonary arterial hypertension.
- A practical review on carfilzomib in multiple myeloma.
- Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma.
- Efficacy of carfilzomib in the treatment of relapsed and (or) refractory multiple myeloma: a meta-analysis of data from clinical trials.
- Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib