Lymphoplasmacytic lymphoma

Summary

Lymphoplasmacytic lymphoma (MONDO:0000432) is a cancer with 1 cohort gene (4 GWAS associations across 1 studies; 1 CIViC-evidence somatic driver) and 68 clinical trials. Molecularly, MYD88 L265P confers sensitivity to Ibrutinib in Lymphoplasmacytic Lymphoma (CIViC Level B); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include fludarabine phosphate, idelalisib, and doxorubicin.

At a glance

• Classification: Cancer
• Cohort genes: 1
• GWAS associations: 4
• Clinical trials: 68
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphoplasmacytic lymphoma
Mondo ID	MONDO:0000432
DOID	DOID:0050747
ICD-11	2058944823
NCIT	C3212
UMLS	C0334633
MedGen	473052
GARD	0022769
Is cancer (heuristic)	yes

Also known as: Immunocytoma, lymphoplasmacytic type · lymphoma, lymphoplasmacytic, malignant · lymphoma, plasmacytic · lymphoplasmacytic lymphoma · lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) · lymphoplasmacytoid lymphoma

Data availability: 4 GWAS associations (1 study).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › B-cell neoplasm › lymphoplasmacytic lymphoma

Related subtypes (4): neoplasm of mature B-cells, B-cell non-Hodgkin lymphoma, high-grade B-cell lymphoma double-hit/triple-hit, large B-cell lymphoma

Subtypes (1): Waldenstrom macroglobulinemia

Genetics & variants

GWAS landscape

4 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs117972357	2e-28	LINC02318	?	20.81
rs550571596	1e-08	FAM184B	A	11.88
rs114087367	1e-07	PKHD1 - MIR206	?	6.27
rs75402334	1e-07	EXOC2	?	26.21

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90624744	Guler M	2025	361	656,254	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	4

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	2

Functional consequences

Consequence	Count
intron_variant	3
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs117972357	14	95577209	G>A		intron_variant	LINC02318	2e-28	Tier 4: intronic/intergenic
rs550571596	4	17674036	T>A	0.003	intron_variant	FAM184B	1e-08	Tier 4: intronic/intergenic
rs114087367	6	52127513	A>C,G		intergenic_variant	PKHD1 - MIR206	1e-07	Tier 4: intronic/intergenic
rs75402334	6	575613	C>T	0.05	intron_variant	EXOC2	1e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
MYD88	Act	CLLSLL,DLBCLNOS,MLYM,NHL	CIViC #3742

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYD88	Orphanet:33226	Waldenström macroglobulinemia
MYD88	Orphanet:70592	Transient predisposition to invasive pyogenic bacterial infection
MYD88	Orphanet:714046	Primary choroidal lymphoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYD88	HGNC:7562	ENSG00000172936	Q99836	Myeloid differentiation primary response protein MyD88	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYD88	Myeloid differentiation primary response protein MyD88	Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYD88	Other/Unknown	no		TIR_dom, Death_dom, DEATH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYD88	284	ubiquitous	marker	leukocyte, mononuclear cell, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYD88	404

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYD88	Q99836	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MyD88 deficiency (TLR5)	1	5710.0×	0.006	MYD88
IRAK4 deficiency (TLR5)	1	2855.0×	0.006	MYD88
p75NTR signals via NF-kB	1	1903.3×	0.006	MYD88
DEx/H-box helicases activate type I IFN and inflammatory cytokines production	1	1631.4×	0.006	MYD88
ZBP1(DAI) mediated induction of type I IFNs	1	1038.2×	0.006	MYD88
p75NTR recruits signalling complexes	1	878.5×	0.006	MYD88
Diseases of Immune System	1	878.5×	0.006	MYD88
Diseases associated with the TLR signaling cascade	1	878.5×	0.006	MYD88
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	1	878.5×	0.006	MYD88
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.006	MYD88
MyD88 deficiency (TLR2/4)	1	601.0×	0.006	MYD88
IRAK4 deficiency (TLR2/4)	1	571.0×	0.006	MYD88
Antigen processing-Cross presentation	1	317.2×	0.010	MYD88
Cytosolic sensors of pathogen-associated DNA	1	285.5×	0.010	MYD88
Negative regulation of the PI3K/AKT network	1	278.5×	0.010	MYD88
Interleukin-1 family signaling	1	271.9×	0.010	MYD88
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.010	MYD88
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.010	MYD88
MyD88 cascade initiated on plasma membrane	1	203.9×	0.010	MYD88
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.010	MYD88
MyD88 dependent cascade initiated on endosome	1	190.3×	0.010	MYD88
p75 NTR receptor-mediated signalling	1	187.2×	0.010	MYD88
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.010	MYD88
Toll Like Receptor 9 (TLR9) Cascade	1	175.7×	0.010	MYD88
Toll Like Receptor TLR6:TLR2 Cascade	1	175.7×	0.010	MYD88
Toll Like Receptor 2 (TLR2) Cascade	1	173.0×	0.010	MYD88
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.010	MYD88
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.010	MYD88
Death Receptor Signaling	1	139.3×	0.011	MYD88
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.011	MYD88

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to molecule of fungal origin	1	16852.0×	0.001	MYD88
induced systemic resistance	1	16852.0×	0.001	MYD88
regulation of chemokine (C-X-C motif) ligand 1 production	1	16852.0×	0.001	MYD88
toll-like receptor 5 signaling pathway	1	8426.0×	0.001	MYD88
leukocyte activation involved in inflammatory response	1	5617.3×	0.001	MYD88
toll-like receptor 8 signaling pathway	1	5617.3×	0.001	MYD88
regulation of chemokine (C-X-C motif) ligand 2 production	1	5617.3×	0.001	MYD88
toll-like receptor TLR6:TLR2 signaling pathway	1	4213.0×	0.001	MYD88
neutrophil-mediated killing of bacterium	1	4213.0×	0.001	MYD88
regulation of neutrophil migration	1	4213.0×	0.001	MYD88
Toll signaling pathway	1	2407.4×	0.002	MYD88
response to peptidoglycan	1	2407.4×	0.002	MYD88
positive regulation of interleukin-23 production	1	2407.4×	0.002	MYD88
interleukin-33-mediated signaling pathway	1	2106.5×	0.002	MYD88
neutrophil activation involved in immune response	1	1872.4×	0.002	MYD88
response to amine	1	1872.4×	0.002	MYD88
positive regulation of lymphocyte proliferation	1	1872.4×	0.002	MYD88
microglia differentiation	1	1532.0×	0.002	MYD88
establishment of endothelial intestinal barrier	1	1404.3×	0.002	MYD88
cellular response to oxidised low-density lipoprotein particle stimulus	1	1404.3×	0.002	MYD88
response to amino acid	1	991.3×	0.003	MYD88
MyD88-dependent toll-like receptor signaling pathway	1	936.2×	0.003	MYD88
interleukin-1-mediated signaling pathway	1	802.5×	0.003	MYD88
positive regulation of macrophage cytokine production	1	732.7×	0.003	MYD88
immunoglobulin mediated immune response	1	702.2×	0.003	MYD88
3’-UTR-mediated mRNA stabilization	1	702.2×	0.003	MYD88
positive regulation of interleukin-17 production	1	601.9×	0.004	MYD88
defense response to protozoan	1	601.9×	0.004	MYD88
positive regulation of NLRP3 inflammasome complex assembly	1	581.1×	0.004	MYD88
positive regulation of cytokine production involved in inflammatory response	1	543.6×	0.004	MYD88

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYD88	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MYD88	26	Binding:26

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MYD88

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MYD88	26	—

Clinical trials & evidence

Clinical trials

Clinical trials: 68.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	25
PHASE1	22
PHASE1/PHASE2	9
Not specified	8
PHASE3	2
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04799275	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma
NCT00566332	PHASE3	COMPLETED	Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia
NCT00801281	PHASE3	COMPLETED	First-line R-CVP vs R-CHOP Induction Immunochemotherapy for Indolent Lymphoma and R Maintenance.
NCT02339922	PHASE2	ACTIVE_NOT_RECRUITING	Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma
NCT02952508	PHASE2	ACTIVE_NOT_RECRUITING	Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom
NCT03015896	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma
NCT03277729	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
NCT03314974	PHASE2	RECRUITING	Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
NCT03674411	PHASE2	ACTIVE_NOT_RECRUITING	Trial Evaluating MGTA-456 in Patients With High-Risk Malignancy
NCT04195633	PHASE2	RECRUITING	Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
NCT04840602	PHASE2	RECRUITING	Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma
NCT04883437	PHASE2	RECRUITING	Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas
NCT05281809	PHASE2	RECRUITING	Local Manufacture of CAR T-Cell Products for the Treatment of B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia
NCT06986174	PHASE2	RECRUITING	A Phase 2 Study to Evaluate the Safety and Efficacy of Pacritinib in Relapsed or Refractory Waldenström Macroglobulinemia
NCT07231952	PHASE2	RECRUITING	A Study of Pirtobrutinib, Venetoclax, and Rituximab in People With Waldenström’s Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
NCT07249905	PHASE1/PHASE2	RECRUITING	Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
NCT07387471	PHASE2	RECRUITING	Study to Assess Change in Disease Activity of Oral Venetoclax in Adult Participants With Recurring Relapsed or Refractory (R/R) Waldenström Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
NCT00142116	PHASE2	COMPLETED	Thalidomide and Rituximab in Waldenstrom’s Macroglobulinemia
NCT00142129	PHASE2	COMPLETED	Bortezomib (Velcade) in Waldenstrom’s Macroglobulinemia
NCT00142181	PHASE2	COMPLETED	Phase II Study of Campath-1H Antibody to Treat Waldenstrom’s Macroglobulinemia
NCT00644189	PHASE1/PHASE2	COMPLETED	Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma
NCT00719888	PHASE2	COMPLETED	Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With Hematologic Disease
NCT00723099	PHASE2	COMPLETED	Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
NCT01076543	PHASE1/PHASE2	COMPLETED	Lenalidomide and Temsirolimus in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma
NCT01163201	PHASE1/PHASE2	WITHDRAWN	T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies
NCT01282424	PHASE2	COMPLETED	Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin Lymphomas
NCT01314014	PHASE2	COMPLETED	Imexon for Relapsed Follicular and Aggressive Lymphomas
NCT01474681	PHASE1/PHASE2	COMPLETED	Safety and Tolerability of HSC835 in Patients With Hematological Malignancies
NCT02332980	PHASE2	COMPLETED	Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas
NCT02661035	PHASE2	COMPLETED	Allo HSCT Using RIC for Hematological Diseases
NCT02722668	PHASE2	COMPLETED	UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep
NCT02991898	PHASE2	TERMINATED	Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies
NCT03010358	PHASE1/PHASE2	COMPLETED	Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma
NCT03037645	PHASE1/PHASE2	TERMINATED	Safety, PK, PD, and Antitumor Activity of Vecabrutinib (SNS-062) in B Lymphoid Cancers
NCT03133221	PHASE2	COMPLETED	1630GCC: Zydelig Maintenance in B-Cell Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation
NCT03335098	PHASE2	UNKNOWN	Study of VTD in Waldenstrom’s Macroglobulinemia
NCT04191187	PHASE2	COMPLETED	Reduced Intensity Flu/Mel/TBI Conditioning for HAPLO HCT Patients With Hematologic Malignancies
NCT01209871	PHASE1	ACTIVE_NOT_RECRUITING	Vaccine Therapy in Treating Patients With Lymphoplasmacytic Lymphoma
NCT01955499	PHASE1	ACTIVE_NOT_RECRUITING	Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
NCT02153580	PHASE1	ACTIVE_NOT_RECRUITING	Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	13
IDELALISIB	4	4
DOXORUBICIN	4	2
PACRITINIB	4	2
ACALABRUTINIB	4	1
ALEMTUZUMAB	4	1
AZACITIDINE	4	1
BENDAMUSTINE HYDROCHLORIDE	4	1
CHLORAMBUCIL	4	1
CLOFARABINE	4	1
COPANLISIB	4	1
IBRUTINIB	4	1
IXAZOMIB CITRATE	4	1
MYCOPHENOLATE SODIUM	4	1
OBINUTUZUMAB	4	1
PIRTOBRUTINIB	4	1
TEMSIROLIMUS	4	1
THIOTEPA	4	1
TREOSULFAN	4	1
UBLITUXIMAB	4	1
UMBRALISIB	4	1
VINCRISTINE	4	1
ZANUBRUTINIB	4	1
CIRMTUZUMAB	3	1
ENTOSPLETINIB	3	1
FLUDARABINE	3	1
PEVONEDISTAT	3	1
CDX-1140	2	1
CDX-301	2	1
IMEXON	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items; also 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
MYD88 L265P	Ibrutinib	Sensitivity/Response	CIViC B	EID986
MYD88 L265P	IRAK-1/4 Inhibitor + IMG-2005-5	Sensitivity/Response	CIViC D	EID1641