Substances tested

What has been given to the plasmocyte, and what the cell did. Research reference, not medical advice.

All substances 32

Bortezomib proteasome inhibitor, reversible boronic acid

acts on 20S proteasome, beta-5 subunit

Blocks proteasomal degradation of misfolded immunoglobulin chains. The plasmocyte already runs its endoplasmic reticulum near capacity, so the undegraded load tips it into terminal ER stress and apoptosis. This is why the cell that secretes the most protein is the cell most sensitive to proteasome inhibition. First proteasome inhibitor approved, 2003.

dose: not stated in the abstract · human, multiple myeloma · review of mechanism, resistance patterns and combination regimens · Ito S. Proteasome Inhibitors for the Treatment of Multiple Myeloma. Cancers (Basel). 2020;12(2). PMID: 31979059 · source

Carfilzomib proteasome inhibitor, irreversible epoxyketone

acts on 20S proteasome, beta-5 subunit, selective

Binds the beta-5 subunit irreversibly rather than reversibly, giving more sustained proteasome blockade than bortezomib and activity in bortezomib-refractory disease.

dose: not stated in the abstract · human, relapsed and refractory multiple myeloma · review · Ito S. Proteasome Inhibitors for the Treatment of Multiple Myeloma. Cancers (Basel). 2020;12(2). PMID: 31979059 · source

Ixazomib proteasome inhibitor, oral boronic acid

acts on 20S proteasome, beta-5 subunit

The first orally available proteasome inhibitor, same mechanistic class as bortezomib.

dose: not stated in the abstract · human, multiple myeloma · review · Ito S. Proteasome Inhibitors for the Treatment of Multiple Myeloma. Cancers (Basel). 2020;12(2). PMID: 31979059 · source

Lenalidomide immunomodulatory drug (IMiD)

acts on cereblon, substrate receptor of the CRL4-CRBN ubiquitin ligase

Binds cereblon and redirects the CRL4-CRBN ubiquitin ligase onto IKZF1 (Ikaros) and IKZF3 (Aiolos), transcription factors the myeloma plasmocyte needs to survive. Degrading them kills the cell. Intrinsic and acquired loss of cereblon is the main route to resistance.

dose: not stated in the abstract · human, multiple myeloma · review of mechanism and clinical experience · Holstein SA, McCarthy PL. Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience. Drugs. 2017;77(5):505-520. PMID: 28205024 · source

Thalidomide immunomodulatory drug (IMiD)

acts on cereblon, CRL4-CRBN ubiquitin ligase

Same cereblon-directed mechanism as lenalidomide and pomalidomide: degradation of IKZF1 and IKZF3.

dose: not stated in the abstract · human, multiple myeloma · review · Holstein SA, McCarthy PL. Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience. Drugs. 2017;77(5):505-520. PMID: 28205024 · source

Pomalidomide immunomodulatory drug (IMiD)

acts on cereblon, CRL4-CRBN ubiquitin ligase

Same cereblon-directed degradation of IKZF1 and IKZF3; used in later lines, including after lenalidomide.

dose: not stated in the abstract · human, multiple myeloma · review · Kulig P, Milczarek S, Bakinowska E, Szalewska L, Baumert B, Machalinski B. Lenalidomide in Multiple Myeloma: Review of Resistance Mechanisms, Current Treatment Strategies and Future Perspectives. Cancers (Basel). 2023;15(3). PMID: 36765919 · source

Daratumumab anti-CD38 monoclonal antibody, humanised IgG1 kappa

acts on CD38, constitutively high on the plasmocyte from the plasmablast stage onward

Kills the plasmocyte by complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity; bone marrow stromal cells do not block either. Separately, it depletes CD38-positive regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, relieving immunosuppression and expanding T cell numbers in treated patients.

dose: 16 mg/kg monotherapy in the phase II trial cited at first approval, giving about 30 percent overall response · human, multiple myeloma; in vitro and patient samples · CDC and ADCC assays; flow cytometry and T cell repertoire sequencing in treated patients · de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186(3):1840-8. PMID: 21187443 | Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128(3):384-94. PMID: 27222480 | McKeage K. Daratumumab: First Global Approval. Drugs. 2016;76(2):275-81. PMID: 26729183 · source

Isatuximab anti-CD38 monoclonal antibody

acts on CD38, at an epitope distinct from the daratumumab epitope

Binds CD38 non-competitively with respect to daratumumab: epitope mapping places the two on distinct, non-overlapping epitopes, which raises the possibility of sequential use.

dose: not stated in the abstract · human, multiple myeloma · epitope mapping · Osuna-Gómez R, López-Pardo J, Mulet M, Nomdedéu J, Cantó E, Ortin R et al. Non-Competitive Binding of Isatuximab and Daratumumab to CD38: Implications for Targeted Therapy in Multiple Myeloma. Pharmaceutics. 2025;17(10):1278. PMID: 41155915 · source

Teclistamab bispecific antibody, BCMA x CD3

acts on BCMA (TNFRSF17) on the plasmocyte, CD3 on T cells

Bridges a T cell to the plasmocyte through BCMA, which is expressed almost exclusively on plasmocytes and plasmablasts. MajesTEC-1 reported 63 percent overall response with 39 percent at or above complete response. Loss of BCMA and T cell exhaustion are the principal resistance routes.

dose: not stated in the abstract · human, relapsed or refractory multiple myeloma · clinical trial review; longitudinal resistance analysis · Piron B, Moreau P, Touzeau C. Teclistamab for Relapsed or Refractory Multiple Myeloma: A Review of Efficacy, Safety, Resistance Mechanisms and Future Directions. Biologics. 2026;20:539066. PMID: 41551208 | Vishwamitra D, Skerget S, Cortes-Selva D, Perova T, Lau O, Davis C et al. Longitudinal mechanisms of response, resistance and relapse to teclistamab in multiple myeloma: results from MajesTEC-1. Haematologica. 2026. PMID: 42273947 · source

Elranatamab bispecific antibody, BCMA x CD3

acts on BCMA on the plasmocyte, CD3 on T cells

Same BCMA-directed T cell engagement as teclistamab. The MagnetisMM-1 phase 1 dose-escalation reported 64 percent overall response in triple-class-refractory patients; extended MagnetisMM-3 follow-up confirms durable responses.

dose: recommended dose established in the phase 1 dose escalation; the value is not stated in the abstract · human, relapsed or refractory multiple myeloma · phase 1 dose-escalation trial; extended follow-up · Bahlis NJ, Costello CL, Raje NS, Levy MY, Dholaria B, Solh M et al. Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial. Nat Med. 2023;29(10):2570-2576. PMID: 37783970 | Tomasson MH, Iida S, Niesvizky R, Mohty M, Bahlis NJ, Martinez-Lopez J et al. Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM-3 study. Hemasphere. 2024;8(7):e136. PMID: 39055646 · source

Ciltacabtagene autoleucel BCMA-directed autologous CAR T cell therapy

acts on BCMA, engaged by two distinct BCMA-binding single-chain variable domains with 4-1BB co-stimulation

A single infusion produced 97.9 percent overall response and 82.5 percent stringent complete response at two-year follow-up in heavily pretreated patients (CARTITUDE-1), and 84.6 percent overall response in CARTITUDE-4. FDA approved 2022, extended to 1 to 2 prior lines in 2024.

dose: single infusion; cell dose not stated in the abstract · human, relapsed or refractory multiple myeloma · phase 1b/2 trial with two-year follow-up · Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P et al. Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up. J Clin Oncol. 2023;41(6):1265-1274. PMID: 35658469 | Strassl I, Podar K. The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma. Expert Opin Drug Discov. 2024;19(4):377-391. PMID: 38369760 · source

Idecabtagene vicleucel BCMA-directed autologous CAR T cell therapy

acts on BCMA

The pivotal KarMMa phase 2 trial reported 73 percent overall response and 33 percent complete response, leading to the first CAR T approval in myeloma.

dose: single infusion; cell dose not stated in the abstract · human, relapsed and refractory multiple myeloma · phase 2 trial · Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384(8):705-716. PMID: 33626253 · source

Interleukin-6 cytokine, physiological

acts on IL-6 receptor alpha (CD126) paired with gp130

Marrow stromal IL-6 drives STAT3 activation in the plasmocyte, promoting survival, proliferation and protection from apoptosis. In myeloma an autocrine IL-6 loop makes this a therapeutic target. IL-6 is required for normal induction of a plasma cell response but not for its maintenance, so its effect is redundant with other niche signals.

dose: not stated in the abstract · human myeloma cells; mouse for the induction and maintenance distinction · receptor complex and signalling studies; IL-6-deficient mice · Barille S, Bataille R, Amiot M. The role of interleukin-6 and interleukin-6/interleukin-6 receptor-alpha complex in the pathogenesis of multiple myeloma. Eur Cytokine Netw. 2000;11(4):546-51. PMID: 11125296 | Cassese G, Arce S, Hauser AE, Lehnert K, Moewes B, Mostarac M et al. Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J Immunol. 2003;171(4):1684-90. PMID: 12902466 · source

APRIL and BAFF TNF-family ligands, physiological

acts on BCMA (TNFRSF17)

Bind BCMA on plasmocytes and plasmablasts and trigger NF-kB and PI3K survival signalling. BCMA expression is near-exclusive to this lineage, which is what makes it a clean therapeutic target.

dose: not stated in the abstract · human, multiple myeloma · expression and signalling analysis · Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689-94. PMID: 14512299 · source

Oligomeric APRIL and BAFF TNF-family ligands, physiological

acts on TACI (TNFRSF13B)

TACI is activated solely by the oligomeric forms of BAFF and APRIL, unlike BAFF-R which responds to the monomer. This supports survival of activated B cells and plasmablasts at germinal centre exit. Loss-of-function TACI mutations cause common variable immunodeficiency.

dose: not stated in the abstract · human and mouse · receptor activation assays with defined ligand oligomeric states · Bossen C, Cachero TG, Tardivel A, Ingold K, Willen L, Dobles M et al. TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts. Blood. 2008;111(3):1004-12. PMID: 17942754 · source

CXCL12 (SDF-1 alpha) chemokine, physiological

acts on CXCR4

Stromal CXCL12 holds the plasmocyte in its marrow survival niche through CXCR4. Disrupting the axis mobilises plasmocytes out of the marrow into circulation, which is how plerixafor is used to mobilise myeloma cells. CXCL12 also acts as one of the synergistic survival signals of the niche.

dose: not stated in the abstract · mouse, NZB/W · homing and survival studies · Cheng Q, Khodadadi L, Taddeo A, Klotsche J, Hoyer BF, Radbruch A et al. CXCR4-CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice. Eur J Immunol. 2018;48(6):1020-1029. PMID: 29427452 · source

Dexamethasone glucocorticoid

acts on glucocorticoid receptor (NR3C1); induces apoptosis in MAF and MMSET subgroup myeloma plasma cells; CCND1 subgroup resistant

cytotoxic in glucocorticoid-receptor-expressing myeloma plasma cells; pro-apoptotic in sensitive subgroups, no effect in CCND1-overexpressing lines

dose: high-dose clinical use; IC50 varies by molecular subgroup in vitro · human myeloma cell lines and primary patient samples · in vitro viability assay; molecular subgroup stratification by FISH and gene expression · Kervoelen C, Menoret E, Gomez-Bougie P, Bataille R, Godon C, Marionneau-Lambot S et al. Dexamethasone-induced cell death is restricted to specific molecular subgroups of multiple myeloma. Oncotarget. 2015;6(29):26922-34. PMID: 26323097 · [object Object]

Venetoclax BCL2 inhibitor

acts on BCL2, anti-apoptotic protein overexpressed in t(11;14) plasma cells; BIM displacement from BCL2 is the proximal apoptotic trigger

induces apoptosis selectively in BCL2-dependent t(11;14) myeloma plasma cells; MCL1-dependent lines resistant; BIM knockout reduces sensitivity

dose: 400-800 mg orally daily in combination regimens (clinical phase III) · human (myeloma cell lines and patient samples); phase III trial · randomised phase III trial (BELLINI); BH3 profiling; RNA-seq subgroup analysis · Gupta VA, Barwick BG, Matulis SM, Shirasaki R, Jaye DL, Keats JJ et al. Venetoclax sensitivity in multiple myeloma is associated with B-cell gene expression. Blood. 2021;137(26):3604-3615. PMID: 33649772 · [object Object]

Belantamab mafodotin antibody-drug conjugate (ADC)

acts on BCMA (TNFRSF17) on the plasmocyte surface; MMAF payload delivered after receptor internalisation

direct cytotoxicity via microtubule disruption; immunogenic cell death; activates NK cell-mediated ADCC in vivo

dose: 2.5 mg/kg IV every 3 weeks (approved dose); phase II DREAMM-2 · human (in vitro and in vivo mouse xenograft; clinical) · in vitro cytotoxicity; flow cytometry; syngeneic and xenograft mouse models; phase II clinical trial · Montes de Oca R, Alavi AS, Vitali N, Bhattacharya S, Blackwell C, Patel K et al. Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021;20(10):1941-1955. PMID: 34253590 · [object Object]

Panobinostat pan-HDAC inhibitor

acts on class I, II and IV histone deacetylases; increases histone acetylation, induces cell cycle arrest and apoptosis in myeloma plasma cells

anti-proliferative and pro-apoptotic in myeloma; synergistic with bortezomib (aggresome pathway disruption); approved in combination with bortezomib + dexamethasone

dose: 20 mg orally three times per week on weeks 1 and 2 of each 21-day cycle · human (clinical pharmacokinetics); myeloma cell lines · phase III PANORAMA trials; pharmacokinetic modelling; Cmax 21.6 ng/mL after 20 mg oral dose · Van Veggel M, Westerman E, Hamberg P. Clinical Pharmacokinetics and Pharmacodynamics of Panobinostat. Clin Pharmacokinet. 2018;57(1):21-29. PMID: 28667459 · [object Object]

Melphalan (high-dose conditioning) alkylating agent, nitrogen mustard

acts on DNA; crosslinks guanine N7 positions, causing double-strand breaks; myeloma plasma cells are acutely sensitive during the G1-S transition after HSC mobilisation

high-dose melphalan (200 mg/m2) followed by autologous stem cell transplantation remains the standard consolidation for eligible patients; in the IFM 2009 RVD trial it deepened responses achieved with induction. Transplant consolidation approximately doubled VGPR rate and tripled stringent complete response rate compared to induction alone.

dose: 200 mg/m2 intravenously as a single conditioning dose before stem cell reinfusion · human, transplant-eligible newly diagnosed multiple myeloma · randomised phase III trial comparing RVD alone vs RVD then high-dose melphalan + ASCT then lenalidomide maintenance (IFM 2009, NEJM 2017) · Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017;376(14):1311-1320. PMID: 28379796 · source

Iberdomide (CC-220) cereblon E3 ligase modulator (CELMoD), third-generation

acts on cereblon (CRBN), substrate receptor of the CRL4-CRBN E3 ubiquitin ligase; iberdomide binds cereblon with higher affinity than lenalidomide or pomalidomide and recruits Ikaros (IKZF1) and Aiolos (IKZF3) for proteasomal degradation with roughly 10-fold greater potency

degrades IKZF1 and IKZF3 at lower concentrations than earlier IMiDs; retains activity in some lenalidomide- and pomalidomide-resistant lines with reduced CRBN expression; also degrades ZFP91 (an additional substrate not substantially engaged by earlier IMiDs), contributing to a distinct resistance profile. In phase I/II combination trials, responses were observed in triple-class-refractory patients.

dose: not stated in the abstract for each combination; phase I dose escalation ongoing at time of the review cited · human myeloma cell lines and clinical trial · biochemical binding assays; substrate degradation by immunoblot; clinical phase I/II data reviewed in 30-year IMiD/CELMoD overview · Bazarbachi AH, Lentzsch S, Facon T, Harousseau JL, Mohty M. Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in Multiple Myeloma: 30 Years in the Making. J Clin Oncol. 2026;44(29):2848-2864. PMID: 42721415 · source

Selinexor selective inhibitor of nuclear export (SINE)

acts on Exportin-1 (XPO1); traps tumour suppressors (p53, IkappaB) and onco-mRNAs in the nucleus of myeloma plasma cells

induces apoptosis in heavily pre-treated myeloma; restores nuclear p53 and IkappaB; approved for penta-refractory myeloma (STORM trial)

dose: 80 mg orally twice weekly in combination with dexamethasone 20 mg · human (clinical) · phase II STORM and phase III BOSTON trials; immunohistochemistry for nuclear localisation · Huang Q, Zhao R, Xu L, Hao X, Tao S. Treatment of multiple myeloma with selinexor: a review. Ther Adv Hematol. 2024;15:20406207231219442. PMID: 38186637 · [object Object]

AMD3100 (plerixafor) CXCR4 antagonist

acts on CXCR4 on the plasmocyte; blocks interaction with stromal CXCL12 that anchors plasma cells in bone marrow niches

displaces long-lived plasma cells from bone marrow survival niches; reduces total ASC number in spleen and bone marrow by over 60% within two weeks in lupus mice; synergistic with bortezomib

dose: continuous CXCR4 blockade for five months in mouse model · NZB/W lupus mouse · adoptive transfer; AMD3100 treatment; bone marrow ELISPOT; survival analysis · Cheng Q, Khodadadi L, Taddeo A, Klotsche J, Hoyer BF, Radbruch A et al. CXCR4-CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice. Eur J Immunol. 2018;48(6):1020-1029. PMID: 29427452 · [object Object]

IL-6 (endogenous cytokine) cytokine; survival signal

acts on IL-6 receptor alpha (gp80)/gp130 complex on the plasmocyte; activates JAK1/2 and STAT3; STAT3 drives c-myc and pim for survival and G1-S transition

proliferation, survival and differentiation of B cells into antibody-forming plasma cells; constitutively active in myeloma; gp130/STAT3 pathway essential for plasma cell neoplasia

dose: endogenous autocrine and paracrine concentrations in bone marrow microenvironment · human and mouse · genetic knockout, dominant-negative STAT3; myeloma cell line models · Hirano T, Ishihara K, Hibi M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 2000;19(21):2548-56. PMID: 10851053 · [object Object]

Elotuzumab immunostimulatory monoclonal antibody

acts on SLAMF7 (CS1/CD319), highly expressed on plasma cells and natural killer (NK) cells; activates NK cells and mediates ADCC against myeloma plasma cells

enhances NK-mediated killing of SLAMF7+ myeloma plasma cells; no direct cytotoxicity as single agent; synergistic with lenalidomide and dexamethasone (ELOQUENT-2: 68% vs 57% PFS at 1 year)

dose: 10 mg/kg IV weekly cycles 1-2, then every 2 weeks · human (clinical) · phase III ELOQUENT-2 randomised trial; NK cell activation assays · Rajkumar SV. Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2024;99(9):1802-1824. PMID: 38943315 · [object Object]

Talquetamab bispecific T-cell engager (TCE)

acts on GPRC5D on the plasmocyte surface (orphan G-protein-coupled receptor enriched on myeloma plasma cells) and CD3 on T cells

redirects T cells to kill GPRC5D+ myeloma plasma cells; 74% overall response rate in penta-refractory patients (MonumenTAL-1 trial)

dose: 0.4 mg/kg subcutaneous weekly or 0.8 mg/kg every two weeks · human (clinical) · phase I/II MonumenTAL-1 trial; flow cytometry for GPRC5D expression · Rajkumar SV. Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2024;99(9):1802-1824. PMID: 38943315 · [object Object]

Teclistamab (MajesTEC-1 China cohort, 2-year follow-up) bispecific antibody, BCMA x CD3

acts on BCMA (TNFRSF17) on the plasmocyte surface; CD3 epsilon on T cells; subcutaneous step-up dosing to reduce cytokine release syndrome

at 2-year follow-up of the MajesTEC-1 China cohort (n=34), overall response rate 64.7%; median duration of response 13.8 months; infections the principal toxicity (73.5% grade 3 or higher), consistent with the global cohort. The China cohort confirms efficacy and safety in an Asian patient population.

dose: step-up dosing: 0.06 mg/kg then 0.3 mg/kg subcutaneous, then 1.5 mg/kg subcutaneous weekly · human, relapsed or refractory multiple myeloma · 2-year follow-up of phase I/II MajesTEC-1 China cohort; primary endpoint overall response rate · Cai Z, Xia Z, He A, Dong Y, Wang Y, Liao A et al. Efficacy and Safety of Teclistamab in Relapsed/Refractory Multiple Myeloma: 2-Year Follow-Up From MajesTEC-1 China Cohort. EJHaem. 2026;7(4):e70340. PMID: 42534634 · source

Isatuximab (ICARIA-MM phase 3) anti-CD38 monoclonal antibody

acts on CD38 on the plasmocyte surface; the isatuximab epitope is distinct from the daratumumab epitope; mechanism includes direct apoptosis, CDC, ADCC and ADCP

isatuximab plus pomalidomide and low-dose dexamethasone (Isa-Pd) improved progression-free survival vs Pd alone in relapsed/refractory myeloma (ICARIA-MM): median PFS 11.5 vs 6.5 months, hazard ratio 0.596; overall response 60.4% vs 35.3%

dose: 10 mg/kg IV weekly for 4 weeks then every 2 weeks · human, relapsed and refractory multiple myeloma (2+ prior lines including lenalidomide and a PI) · randomised, multicentre, open-label phase 3 trial (ICARIA-MM); primary endpoint PFS by IRC · Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019;394(10214):2096-2107. PMID: 31735560 · source

Carfilzomib (ASPIRE + ENDEAVOR deep responder subgroup) proteasome inhibitor, irreversible epoxyketone

acts on 20S proteasome beta-5 subunit; irreversible covalent binding distinguishes it from the reversible boronic acid bortezomib

deep responders (VGPR or better) to carfilzomib-based therapy had longer overall survival than those achieving PR or less; the subgroup analysis across ASPIRE (KRd vs Rd) and ENDEAVOR (Kd vs Vd) confirms that depth of response is prognostically informative specifically for carfilzomib combinations, and supports VGPR as a meaningful endpoint

dose: ASPIRE: 27 mg/m2 IV day 1/2 and 8/9/15/16 of each 28-day cycle; ENDEAVOR: 56 mg/m2 IV · human, relapsed and refractory multiple myeloma · pooled subgroup analysis of phase III ASPIRE and ENDEAVOR trials; landmark OS from response assessment · Weisel K, Mateos MV, Gay F, Delforge M, Cook G, Szabo Z et al. Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR. Leukemia. 2021;35(6):1732-1744. PMID: 33067574 · source

Pomalidomide + dexamethasone (real-world multicenter) immunomodulatory drug (IMiD), third-generation cereblon modulator

acts on cereblon (CRBN); degrades IKZF1 and IKZF3; pomalidomide retains activity in some lenalidomide-refractory cases due to distinct binding affinity and substrate recruitment kinetics

in a real-world multicenter retrospective cohort (Taiwan, n=103), pomalidomide plus low-dose dexamethasone (Pd) achieved 32% overall response in heavily pretreated, lenalidomide-refractory patients; median PFS 4.7 months; the real-world outcomes are lower than phase III but confirm meaningful activity in lenalidomide-refractory plasma cell malignancies outside trial conditions

dose: pomalidomide 4 mg orally days 1-21 of 28-day cycles; dexamethasone 40 mg weekly · human, relapsed or refractory multiple myeloma · multicenter retrospective cohort study; real-world population including renal-impaired and high-cytogenetic-risk patients · Hung YC, Gau JP, Huang SY, Ko BS, Teng CJ. Pomalidomide and Dexamethasone Are Effective in Relapsed or Refractory Multiple Myeloma in a Real-Life Setting: A Multicenter Retrospective Study in Taiwan. Front Oncol. 2021;11:695410. PMID: 34123862 · source

Venetoclax + bortezomib + dexamethasone (VenBd) combination: BCL2 inhibitor + proteasome inhibitor + glucocorticoid

acts on BCL2 (venetoclax), 20S proteasome (bortezomib), glucocorticoid receptor (dexamethasone); triple convergence on the apoptotic pathway of myeloma plasma cells

significant PFS improvement in t(11;14) subgroup (phase III BELLINI); PFS not improved in unselected population, balanced by excess infections; t(11;14) remains the biomarker-driven indication

dose: venetoclax 400 mg daily + bortezomib 1.3 mg/m2 + dexamethasone 20 mg per standard schedule · human (clinical) · randomised phase III BELLINI trial; molecular subgroup analysis by FISH · Kumar SK, Harrison SJ, Cavo M, de la Rubia J, Popat R, Gasparetto C et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2020;21(12):1630-1642. PMID: 33129376 · [object Object]

Substances that act on the plasmocyte, whether normal or malignant. Every row rests on a PubMed abstract. A dose the abstract does not state is written as such, never guessed. Where a number comes from malignant plasmocytes the species and method columns say so, and it is not mixed with normal-plasmocyte values. Most of the pharmacology of this cell is written in the myeloma literature, which is why so many rows come from it. Research reference, not medical advice. Verification: all 18 PubMed ids in this file were run through check-pubmed.py on 2026-09-12 and every title matched the claim hung on it. That run caught two author attributions written from memory rather than read from the record, Gandolfi for what is Ito S 2020 and Costa for what is Kulig P 2023; both are corrected here and every other cite line was rewritten to the author, year and journal NCBI returns. This file is seeded from audited sources and will be extended from the sweep corpus.