Question:
My wife has Waldenström macroglobulinemia, which is a rare non-Hodgkin's lymphoma that affects white blood cells. Is there any data on ivermectin, mebendazole, fenbendazole, or other repurposed drugs that help with reversing this type of blood cancer?
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Overall, just over 7,000 papers have been published on WM. So far, I haven’t found any that mention mebendazole, fenbendazole, or ivermectin. Tomorrow, we’ll look for anecdotal cases outside the medical literature and contact two doctors to get their perspectives on the topic.
There are also numerous clinical trials worth exploring.
Clinical Trials
https://www.cancer.gov/research/participate/clinical-trials/disease/lymphoma/treatment?pn=1
Lots of clinical trials, 6 pages, worth looking into:
https://clinicaltrials.gov/search?cond=Waldenstr%C3%B6m%20&viewType=Card
Mayo Clinic:
https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-02851&r=1
I’ve pulled and read 30 of the most recent topical papers from PubMed.
Yes, there’s a substantial body of research on Waldenström macroglobulinemia (WM). Based on PubMed results, there are roughly 360 review articles and about 120 clinical trial reports with WM in the title. None include mebendazole or ivermectin. Here are some of the most useful ones:
Overviews and guidelines (good starting points)
Gertz, “Waldenström Macroglobulinemia: 2025 Update on Diagnosis, Risk Stratification, and Management” – American Journal of Hematology, 2025. An annual Mayo Clinic update covering diagnosis (including the MYD88 L265P mutation found in over 90% of patients), prognostic factors, and when to treat versus watch. DOI [included]
Treon, Sarosiek & Castillo, “Diagnosis and Management of Waldenstrom’s Macroglobulinemia” – Hematological Oncology, 2025. From the Dana-Farber Bing Center for WM; focuses on how genetics (MYD88, CXCR4, TP53) shape treatment choice. DOI
Roos-Weil et al., “Waldenström’s macroglobulinemia: The LYSA pragmatic guidelines” – European Journal of Cancer, late 2025. Evidence-based European recommendations for frontline and relapsed disease. DOI
Grunenberg & Buske, “How to manage Waldenström’s macroglobulinemia in 2024” – Cancer Treatment Reviews, 2024. DOI
Saburi & Sekiguchi, “Bing-Neel Syndrome in Waldenström Macroglobulinemia” – Cancers, 2025. On a rare complication where WM cells reach the central nervous system. DOI
Key clinical trials
ASPEN (Phase III), zanubrutinib vs. ibrutinib – first report in Blood, 2020 DOI, and final analysis in JCO, 2023 DOI. Both BTK inhibitors worked well; zanubrutinib had deeper responses and fewer heart-related and other side effects.
Buske et al., B-DRC vs. DRC – JCO, 2023. A large European randomized trial showed that fixed-duration chemoimmunotherapy (with or without bortezomib) remains effective as first-line therapy. DOI
Castillo et al., venetoclax in previously treated WM – JCO, 2021. A Phase II study showing high response rates, including in people who had already received BTK inhibitors. DOI
Tomowiak et al., obinutuzumab + idelalisib in relapsed WM – Blood Advances, 2021. DOI
If you’re new to the topic, the Gertz or Treon reviews are the most readable summaries.
Ivervectin
Based on articles retrieved from PubMed, no published research tests ivermectin as a treatment for Waldenström macroglobulinemia. A general web search also turned up nothing linking the two. Here’s what does exist:
The only PubMed paper mentioning both
Balkhair et al., 2019, International Journal of Infectious Diseases – A case report of a patient who developed a severe parasitic infection (disseminated strongyloidiasis) after chemotherapy for lymphoplasmacytic lymphoma, the lymphoma type that WM belongs to. Ivermectin was used to treat the parasite, not the lymphoma. DOI
Where ivermectin actually matters for lymphoma patients
Ivermectin’s established role here is protecting against Strongyloides, a parasite that can become life-threatening when the immune system is suppressed by lymphoma treatment.
Stanchina et al., 2025, American Journal of Hematology – Screened 1,372 lymphoma patients; about 6% tested positive for Strongyloides, and treating them with ivermectin before therapy largely prevented serious infection. The authors support routine screening. DOI
Möller et al., 2026, International Journal of Infectious Diseases – Another case of this infection during B-cell lymphoma therapy, successfully treated with ivermectin and albendazole. DOI
Ivermectin as an anticancer drug in related blood cancers (early-stage only)
Luo et al., 2026, Apoptosis – Lab and mouse study suggesting ivermectin can kill multiple myeloma cells, especially combined with selinexor. DOI
Siregar et al., 2025 – Two cell-culture studies in acute lymphoblastic leukemia cells (DOI, DOI).
Misirian et al., 2026, Case Reports in Hematology – A MALT lymphoma that went into remission after ivermectin, but the lymphoma was driven by an underlying parasitic infection, so treating the parasite removed the trigger. That mechanism doesn’t apply to WM. DOI
Guilford & Yu, 2026, Integrative Medicine – A six-patient case series (including one myeloma patient) reporting good outcomes with antiparasitic drugs chosen by an electro-acupuncture method. It has no control group and other limitations, so it can’t show the drugs caused the results. Journal page
How to read this evidence
Cell and mouse studies are an early step, and most drugs that look promising there don’t pan out in people. The cell studies above also used ivermectin concentrations generally much higher than standard doses reach in the blood. No human trials of ivermectin in WM exist. In contrast, treatments in earlier papers, such as BTK inhibitors and chemoimmunotherapy, have large randomized trials.
Mebendazole
Based on articles retrieved from PubMed, no published studies test mebendazole in Waldenström macroglobulinemia, whether in lab cells, animals, or patients. The only PubMed match was a veterinary study on parasites in goats that happened to use the word “lymphoplasmacytic” (DOI), so it isn’t relevant.
What exists for mebendazole in related blood cancers (all early-stage)
Golla et al., 2024, Cancers – A Penn State review of deworming drugs in the same family (mebendazole, albendazole, flubendazole) across blood cancers. It explains how they disrupt cell division in lab studies and discusses the hurdles before clinical use. This is the most relevant overview. DOI
He et al., 2018, Experimental Cell Research – Mebendazole slowed acute myeloid leukemia (AML) cells in the lab and in mice, reportedly at concentrations achievable in people. DOI
Yang et al., 2025, Journal of Advanced Research – Another AML lab and mouse study. DOI
Tsakaneli et al., 2026, Cell Death & Disease – Pediatric AML in mice, where mebendazole worked better combined with an MCL1 inhibitor. DOI
Ioakeim-Skoufa et al., 2023, Cancers – A review of randomized trials of repurposed drugs. Mebendazole has been trialed in colorectal cancer, but the authors note these trials were small and limited. DOI
AML is a very different disease from WM. It involves myeloid cells and is fast-growing, while WM is a slow-growing B-cell lymphoma, so these results can’t be assumed to carry over.
Something you may come across online
The web search mainly turned up patient anecdotes. For example, one WM patient on a Reddit forum described taking fenbendazole, a related veterinary dewormer, alongside bendamustine and rituximab and reaching complete response, with the hospital pharmacy reviewing it and raising no objections. Stories like this can’t show what the dewormer contributed, because bendamustine plus rituximab alone produces high response rates in WM.
General Videos:
Waldenström Macroglobulinemia - Earl Nolting’s Story
Mayo Clinic
Waldenström Macroglobulinemia (WM) Treatment: Why Timing Is Essential
Patient Empowerment Network
Exciting developments in Waldenström’s macroglobulinemia: insights from a ‘Meet the Expert’ session
VJHemOnc – Video Journal of Hematology & HemOnc
Introduction to Waldenstrom’s macroglobulinaemia (WM) - European WM Patient Forum 2024
WMUK
Waldenstrom Macroglobulinemia: Symptoms, Progression, and Treatment
Medical Centric Podcast
What Is Waldenström’s Macroglobulinemia? Everything You Need to Know
Talking Cancer with Dr. Roman
Waldenstrom Macroglobulinemia
Osmosis from Elsevier
Waldenström’s Macroglobulinemia
Mechanisms in Medicine
Waldenström Macroglobulinemia: A Rare Blood Cancer
National Organization for Rare Disorders (NORD)
Search Terms
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Waldenström Macroglobulinemia
Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder classified as a subset of lymphoplasmacytic lymphoma (LPL). It is characterized by bone marrow infiltration of clonal lymphocytes, lymphoplasmacytic cells, and plasma cells, along with the secretion of a monoclonal immunoglobulin M (IgM) paraprotein.
1. Genomic Drivers & Pathophysiology
WM is driven by specific somatic mutations that shape its disease biology and treatment response:
MYD88 L265P Mutation: Present in 93%–97% of WM cases. This mutation transactivates Hematopoietic Cell Kinase (HCK), which directly stimulates Bruton tyrosine kinase (BTK) and drives constitutive pro-survival NF-κB signaling.
CXCR4 Mutations: Detected in 30%–40% of patients (almost exclusively alongside MYD88 mutations). CXCR4 mutations (especially nonsense variants) are linked to a higher risk of symptomatic hyperviscosity and slower or reduced responses to covalent BTK inhibitors.
TP53 Alterations: Occur in 2%–3% of treatment-naïve cases and up to 30% of relapsed/refractory cases, conferring adverse outcomes and poorer overall survival.
2. Clinical Manifestations & Complications
Symptoms arise from either direct tissue infiltration by lymphoma cells or the physicochemical and immunological properties of the IgM paraprotein:
Tumor Mass & Marrow Infiltration: Leads to normocytic anemia (fatigue), thrombocytopenia, lymphadenopathy, hepatosplenomegaly, and B-symptoms (unexplained fever, night sweats, weight loss).
Hyperviscosity Syndrome: Pentameric IgM paraproteins increase blood viscosity, leading to mucosal bleeding (epistaxis, gingival bleeding), headaches, dizziness, and visual disturbances from retinal hemorrhages.
IgM-Mediated Autoimmune & Tissue Effects:
Peripheral Neuropathy: Demyelinating sensorimotor neuropathy (often anti-MAG antibody-associated).
Cryoglobulinemia & Cold Agglutinin Disease: Protein precipitation in cold temperatures causing Raynaud’s phenomenon, cutaneous ulcers, or autoimmune hemolytic anemia.
AL Amyloidosis & Tissue Deposition: Extracellular protein deposition in the heart, kidneys, liver, or peripheral nerves.
3. Diagnosis & Differential Spectrum
Diagnosis requires meeting two explicit criteria: a detectable monoclonal IgM paraprotein in serum (regardless of concentration) and ≥10% bone marrow infiltration by clonal lymphoplasmacytic cells.
+----------------------------------------------------------------------------------+
| Disease Entity | Marrow Infiltration | Monoclonal IgM | Symptoms |
+------------------------------+---------------------+----------------+------------+
| IgM MGUS | < 10% | Present | Absent |
| Smoldering (Asymptomatic) WM | ≥ 10% | Present | Absent |
| Active / Symptomatic WM | ≥ 10% | Present | Present |
+----------------------------------------------------------------------------------+(Source:)
Key Diagnostic Exclusions: Lytic bone lesions are extremely rare in WM; their presence suggests IgM Multiple Myeloma (1% of myeloma cases), which lacks MYD88 mutations and features chromosome 14 translocations.
4. Prognosis & Risk Stratification
Prognosis is evaluated using scoring systems such as the IPSS-WM and revised IPSS-WM, which incorporate age, hemoglobin, platelet count, β2-microglobulin, LDH, and monoclonal IgM concentrations.
Comorbidity Impact: Recent large-scale evidence from 17,130 patients highlights that a Charlson Comorbidity Index (CC) ≥ 1 is a critical independent predictor of mortality, as roughly half of all deaths in WM patients stem from non-lymphoma comorbidities.
5. Management & Treatment Paradigm
A. Asymptomatic Disease (Watchful Waiting)
Asymptomatic (smoldering) WM or IgM MGUS should be managed with active surveillance (”watch and wait”) every 3–6 months. Initiating treatment early in asymptomatic patients does not confer a survival advantage.
B. Indications for Therapy
Treatment is initiated only when clinical or laboratory complications arise:
Symptomatic anemia (\(\text{Hb} \le 10\text{ g/dL}\)) or platelets \(< 100,000/\mu\text{L}\)
Symptomatic hyperviscosity syndrome
Bulky (\(\ge 5\text{ cm}\)) or symptomatic lymphadenopathy / organomegaly
Progressive peripheral neuropathy, severe cryoglobulinemia, or cold agglutinin disease
C. First-Line Treatment Options
Targeted BTK Inhibitors: Oral covalent BTK inhibitors like Zanubrutinib or Ibrutinib offer continuous, chemotherapy-free disease control. Zanubrutinib is preferred in patients with CXCR4 mutations or TP53 alterations due to superior deep response rates.
Fixed-Duration Chemoimmunotherapy: Bendamustine + Rituximab (BR) or Dexamethasone + Rituximab + Cyclophosphamide (DRC) offer durable time-limited remissions.
Emergent Interventions & Precautions:
Plasmapheresis (Plasma Exchange): Used immediately to clear circulating IgM and manage severe hyperviscosity.
IgM Flare Caution: Monoclonal anti-CD20 antibodies (Rituximab) can trigger a transient surge in serum IgM (”IgM flare”). If baseline IgM exceeds \(4,000\text{ mg/dL}\), Rituximab should be withheld for the first 1–2 cycles until cytoreductive therapy lowers IgM levels.
D. Relapsed/Refractory & Emerging Therapies
Non-Covalent BTK Inhibitors: Pirtobrutinib overcomes acquired BTK C481S resistance mutations seen after covalent BTK inhibitor therapy.
BTK Degraders: Next-generation targeted degraders (e.g., BGB-16673, NX-5948) eliminate both BTK kinase activity and scaffolding functions.
BCL2 Inhibitors: Venetoclax or Sonrotoclax demonstrate marked activity in heavily pretreated disease.
Novel Immunotherapies: Clinical trials are investigating CD19-targeted antibody-drug conjugates (Loncastuximab tesirine), CD3/CD20 bispecific antibodies (Epcoritamab), and CD19-targeted CAR-NK/CAR-T cell therapies.
Waldenström Therapies
Clinical trials evaluating targeted therapies in Waldenström macroglobulinemia (WM) have reshaped management across both treatment-naïve (TN) and relapsed/refractory (R/R) settings.
1. Covalent BTK Inhibitors (cBTKi) & First-Line Combinations
ASPEN Trial (Zanubrutinib vs. Ibrutinib):
Design & Efficacy: A prospective Phase 3 trial comparing zanubrutinib (160 mg BID) with ibrutinib (420 mg QD). At a 44.4-month median follow-up, zanubrutinib demonstrated an Overall Response Rate (ORR) of 95.9% and a Very Good Partial Response (VGPR) rate of 43.8% versus 19% with ibrutinib. Zanubrutinib achieved higher response quality and improved progression-free survival (PFS) in high-risk subgroups, including patients with CXCR4 mutations or TP53 alterations.
Safety Profile: Zanubrutinib demonstrated significantly lower cardiac toxicity, with an atrial fibrillation incidence of only 2% compared to 15% for ibrutinib, leading to fewer adverse event-related treatment discontinuations.
iNNOVATE Trial (Ibrutinib + Rituximab vs. Placebo + Rituximab):
Outcomes: At a 50-month median follow-up, the addition of ibrutinib to rituximab significantly prolonged median PFS (not reached vs. 20.3 months with placebo + rituximab; HR 0.25) and yielded a 4.5-year PFS rate of 68% vs. 25%. The clinical benefit was maintained across all genomic cohorts, regardless of MYD88 or CXCR4 status.
BRAWM Study (Bendamustine + Rituximab + Acalabrutinib):
Outcomes: In a Phase 2 trial of 63 treatment-naïve patients receiving 1 year of acalabrutinib with 6 cycles of Bendamustine-Rituximab (BR), the combined Complete Response (CR) + VGPR rate reached 59% (59.4% in patients <70 years; 58.1% in patients ≥70 years), with minimal residual disease (MRD) negativity rates of 78.6% and 77.8%, respectively.
ECWM-1 Trial (DRC vs. Bortezomib + DRC in TN WM):
Outcomes: Final analysis of 202 patients demonstrated that adding bortezomib to dexamethasone, rituximab, and cyclophosphamide (B-DRC) achieved numerically higher CR/VGPR rates (35.4% vs. 22.2%) and faster 4-month responses (73% vs. 61%), but did not significantly improve median PFS (56.7 vs. 50.1 months; p=0.64) or 5-year OS (~90% in both arms). B-DRC was associated with a 2.5-fold higher incidence of sensory peripheral neuropathy.
Ibrutinib + Venetoclax (All-Oral Triplet in TN WM):
Outcomes: In 45 treatment-naïve patients, fixed-duration ibrutinib plus venetoclax yielded an ORR of 70%, VGPR rate of 42%, and a median PFS of 36 months. However, the trial was terminated early due to four cases of severe ventricular arrhythmias (including two fatal events), rendering the combination unrecommended in frontline disease.
2. Non-Covalent BTK Inhibitors in Relapsed/Refractory Disease
BRUIN Study (Pirtobrutinib):
Trial Overview: Evaluated pirtobrutinib (200 mg QD), a highly selective non-covalent BTK inhibitor that overcomes covalent BTK resistance mediated by BTK C481 mutations.
Efficacy Outcomes (5-Year Follow-up, n=80): Achieved an ORR of 83%, Major Response Rate (MRR) of 73%, and median PFS of 36 months. Among 63 patients pretreated with covalent BTK inhibitors, pirtobrutinib maintained an 81% ORR, 68% MRR, and a median PFS of 20 months. In BTKi-naïve patients (n=17), ORR and MRR were both 88%, with a 36-month PFS rate of 76%.
Safety Profile: Well tolerated with low rates of cardiac toxicity (Grade ≥3 atrial fibrillation/flutter in 1% [1 patient]; Grade ≥3 hypertension in 4%).
Pirtobrutinib + Venetoclax Combination (Phase 2):
Outcomes: Fixed-duration therapy (24 cycles) in 38 R/R WM patients yielded an ORR of 100% and a VGPR/CR rate of 56% among MYD88-mutant cases, with a 12-month PFS rate of 94%. Grade ≥3 neutropenia occurred in 37% of patients, with no observed cases of tumor lysis syndrome or cardiac arrhythmias.
3. Next-Generation BTK Degraders
BTK degraders utilize proteasomal degradation pathways to eliminate both BTK enzymatic kinase activity and structural scaffolding functions, demonstrating activity across patients with BTK C481S and L528W mutations:
BGB-16673 (CaDAnCe-101 Study):
Outcomes: In 42 heavily pretreated R/R WM patients (median 3 prior lines), single-agent BGB-16673 achieved an ORR of 83.3%, MRR of 64.3%, and VGPR rate of 26.2%. Response rates were independent of BTK, MYD88, CXCR4, TP53, or PLCG2 mutational status, with an 84.1% 9-month Duration of Response (DoR) and no observed atrial fibrillation.
Bexobrutideg / NX-5948 (Phase 1a/b Study):
Outcomes: In 27 cBTKi-exposed WM patients (20 evaluable), bexobrutideg demonstrated an ORR of 85.0% and an MRR of 70.0%, with 42.9% achieving ≥90% serum IgM reduction or normalization. Responses deepened over time and were observed in patients with Bing-Neel syndrome (CNS involvement) without dose-limiting toxicities or severe arrhythmias.
4. BCL2 Inhibitors & Pathway Targets
Venetoclax Monotherapy: Phase 2 evaluation of venetoclax (800 mg daily target dose) in previously treated WM demonstrated an ORR of 87% and MRR of 80%, demonstrating activity in patients with prior cBTKi exposure or CXCR4 mutations.
Sonrotoclax (BGB-11417): Next-generation BCL2 inhibitor evaluated in Phase 1 trials for R/R WM (n=19), achieving an ORR of 79% and MRR of 58%.
SGR-1505 (MALT1 Inhibitor): Phase 1 trial targeting MALT1 downstream in the NF-κB signaling complex achieved a 100% ORR (3 minor responses, 3 partial responses) with rapid IgM reduction in 6 BTKi-refractory WM patients.
5. Novel Immunotherapies & Cellular Therapies
Loncastuximab Tesirine (WM-NET1 Trial):
Outcomes: A CD19-targeted antibody-drug conjugate (ADC) delivering a pyrrolobenzodiazepine (PBD) dimer payload. In 14 heavily pretreated WM patients (median 4 prior lines), 6 cycles achieved an ORR of 93% and VGPR/CR rate of 71%. In eight high-risk TP53-altered patients, ORR was 100% with an 89% VGPR/CR rate.
CD19 t-haNK Cell Therapy (QUILT-106 Trial):
Outcomes: First-in-human trial of an off-the-shelf allogeneic CAR-NK cell therapy ± rituximab in R/R WM. Both evaluable patients achieved profound remissions (1 CR with monotherapy, 1 deep remission with combination), showing >90% IgM reduction and bone marrow clearance without cytokine release syndrome or neurotoxicity.
286 Additional Papers: