Lumoxiti (moxetumomab pasudotox) / AstraZeneca - LARVOL DELTA

Rituximab Reduces Immunogenicity and Increases Complete Remissions without Minimal Residual Disease in Relapsed/Refractory Hairy Cell Leukemia Patients Receiving Moxetumomab Pasudotox (ASH 2024) - "Patients 14-18 received the biosimilar Ruxience instead of rituximab...One multiply relapsed patient with rituximab allergy was treated off-protocol with 8 cycles of Moxe plus Obinutuzumab and achieved an MRD-free CR.Conclusions : MoxeR is a safe regimen for relapsed-refractory HCL/HCLv, with the highest MRD-free CR rate reported yet for this disease...Non-Hodgkin's lymphomas (NHL), such as diffuse large B-cell, mantle cell, marginal zone, follicular, and lymphoplasmacytic lymphoma, express significant levels of CD22, and lymphoma cells from these patients have sensitivity to Moxe similar to HCL. We believe this trial supports the testing of Moxe plus anti-CD20 Mab in patients with early HCL/HCLv, and in patients with NHL to convert MRD-positive to MRD-negative CRs."

Clinical • Minimal residual disease • Residual disease • Atypical Hemolytic Uremic Syndrome • Diffuse Large B Cell Lymphoma • Hairy Cell Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

A Randomized Phase 2 Trial of 2nd-Line Cladribine with Concurrent or Delayed Rituximab in Patients with Classic Hairy Cell Leukemia (ASH 2024) - "Background : Hairy cell leukemia is a B-cell malignancy characterized by pancytopenia, splenomegaly, and long-term remissions to purine analogs cladribine (CDA) and pentostatin, but late relapses occur, presumably from minimal residual disease (MRD)...Two after CDAR vs 4 after CDA (p=0.42) progressed and required alternative therapy, several of whom remain MRD-free after moxetumomab pasudotox with rituximab...Thus, CDA with delayed rituximab at >6 months if/when blood becomes MRD-positive is still reasonable 2nd line treatment of HCL. Delayed rituximab is now being tested to eliminate MRD in patients who achieve MRD-positive CR to MEK +/- BRAF inhibition."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Clinically approved immunotoxins targeting hematological cancers: "the best of both worlds". (PubMed, Front Pharmacol) - "In this review, we analyze three FDA-approved RITs, namely, moxetumomab pasudotox, tagraxofusp, and denileukin diftitox, that utilize bacterial toxins from Pseudomonas and Corynebacterium diphtheriae to treat refractory/relapsed (R/R) HCL, BPDCN, and adult R/R cutaneous T-cell lymphoma (CTCL), respectively. We reviewed their comprehensive safety profiles, describe complications associated with these fusion proteins, and, finally, discuss potential risk management strategies that may enhance their clinical outcomes. Overall, RITs have demonstrated efficacy, and researchers continue to extend these findings to other indications."

Journal • Review • Cutaneous T-cell Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Bacterial Protein Toxins as Anticancer Agents: Clinical Potential of Pseudomonas and Anthrax Toxins. (PubMed, Toxins (Basel)) - "The clinical approval of the PE-based immunotoxin, moxetumomab pasudotox, for the treatment of hairy cell leukemia, underscores the potential of this strategy. This review also discusses current challenges and outlines future directions for the advancement of bacterial toxin-based therapeutics."

Journal • Review • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology • Ophthalmology • Strabismus

Advanced Antibody-Drug Conjugates Design: Innovation in Linker Chemistry and Site-Specific Conjugation Technologies. (PubMed, Chembiochem) - "Several ADCs have been approved for clinical use in oncology, including Mylotarg, Adcetris, Kadcyla, Besponsa, Polivy, Lumoxiti, Padcev, Enhertu, Trodelvy, Aidixi, Zynlonta, Tivdak, Elahere, Datroway, and Emrelis. The toxicity profiles of ADCs and strategies are also addressed to mitigate off-target effects and systemic toxicity. Overall, this review provides a comprehensive overview of the current state of linker and conjugation technologies in ADC development."

Journal • Review • Oncology

Clinically Approved Immunotoxins Targeting Hematological Cancers: "The Best of Both Worlds" (Front Pharmacol) - "In this review, we analyze three FDA-approved RITs, moxetumomab pasudotox, tagraxofusp, and denileukin diftitox, that utilize bacterial toxins from Pseudomonas and Corynebacterium diphtheriae to treat refractory/relapsed (R/R) HCL, BPDCN, adult R/R cutaneous T-cell lymphoma (CTCL), respectively."

Review • Blastic Plasmacytoid Dendritic Cell Neoplasm • Cutaneous T-cell Lymphoma • Hairy Cell Leukemia

Preclinical Study of Development of Novel Radiopharmaceutical Tracers Targeted to NECTIN4 by Labelling Gallium-68 (SNMMI 2025) - "The two high-affinity antibody fragments, both of which were Fab structures, were named N41 and HA22. The radiolabeled probes, 68Ga-NOTA-N41 and 68Ga-NOTA-HA22, were synthesized with high labeling yields of 85.80% ± 9.86% and 86.04% ± 2.53%, respectively. Their radiochemical purity exceeded 95%, and the tracers remained stable for at least 4 hours, as confirmed by HPLC."

Preclinical • Genito-urinary Cancer • Oncology • Solid Tumor

PROGNOSTIC IMPACT OF MEASURABLE RESIDUAL DISEASE IN HAIRY CELL LEUKEMIA: A 30 YEARS SINGLE CENTER EXPERIENCE (EHA 2025) - "There were statistically significant differences in PFS based on the type of therapy [cladribine (2-CdA), pentostatine (DCF), interferon (IFN), moxetumomab pasudotox, rituximab (R), R-2-CdA, R-DCF, R-Vemurafenib)], with the greatest advantage for combination therapies (p=0,0001). In conclusion, MRD eradication has an important prognostic impact in patients with cHCL, since there are not significant differences in terms of PFS between CR and PR, but only between MRD- e MRD+. Notably, our study confirms that MRD negativity is possible to obtain also in pretreated patients."

Clinical • Residual disease • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • B2M

Potential Drug Targets for Chronic Widespread Pain: A proteome-wide Mendelian randomization and drug repurposing analysis (EULAR 2025) - "Notably, CD22 and FAP are already targeted by existing drugs, indicating their potential for repurposing: inotuzumab, ozogamicin and moxetumomab pasudotox; and f19 131i and sibrotuzumab respectively. We identified 8 potential protein targets for CWP, with CD22 and FAP already targeted by existing drugs. These findings provide insights into the molecular mechanisms underlying CWP, and suggest repurposing opportunities for drug development and clinical testing."

Pain • CD22 • FXYD5 • LONP1

A SELECTIVE RESECTION ALGORITHM FOR BARRETT'S NEOPLASIA OPTIMIZES ONCOLOGICAL OUTCOMES (DDW 2025) - "For T1a disease, en-bloc resection (SRA 110 [83.3%] vs HA 22 [48.9%]; P<0.001), R0 excision (SRA 91 [68.9%] vs HA 17 [37.8%]; P<0.001) and curative resection (SRA 77 [58.3%] vs HA 14 [31.1%]; P=0.002) were higher in the SRA cohort... A selective resection algorithm optimizes oncologic outcomes for Barrett's adenocarcinoma and mitigates the risk of piecemeal resection of cancers."

Oncology

Targeting CLIC3 as a novel strategy to inhibit metastasis in breast cancer (AACR 2025) - "Among them, HA-22-31 emerged as a lead compound (IC50 = 1.7 μM), demonstrating direct binding to CLIC3 and significant inhibition of migration.In conclusion, CLIC3 enhances metastasis in breast cancer through its enzymatic activity. These findings suggest that further development of small molecule CLIC3 inhibitors may represent a promising new strategy for targeting metastatic breast cancer."

Breast Cancer • Oncology • Solid Tumor • CLIC3 • TGM2

Effect of rituximab on remissions without minimal residual disease and immunogenicity in patients with relapsed/refractory hairy cell leukemia receiving moxetumomab pasudotox. (ASCO 2024) - P1 | " After 13 patients received Moxe-Rituximab (MoxeR) without dose-limiting toxicity (DLT), meeting the phase 1 endpoint, 5 additional patients received Moxe with the biosimilar Ruxience (MoxeR). Despite enrolling slightly fewer patients than planned, MoxeR was safe and more effective than Moxe alone at achieving MRD-free CR, probably due to lower immunogenicity and faster reduction of HCL/HCLv tumor burden. Since non-Hodgkin's lymphoma (NHL) cells from patients are sensitive to Moxe like HCL, MoxeR could be tested after NHL treatment to convert MRD+ to MRD-free CRs. Clinical trial information: NCT03805932."

Clinical • Minimal residual disease • Residual disease • Atypical Hemolytic Uremic Syndrome • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • CD20

CLIC3 is a new target for metastatic breast cancer (EACR-AACR 2024) - "HA-22-31 is a promising CLIC3i (IC50 = 1.7 μM), directly binds CLIC3 and inhibits migration in a scratch assay. Conclusion CLIC3 promotes metastasis in breast cancer through its enzymatic activity. Given the impacts of CLIC3 knockdown on blocking metastatic breast cancer properties, we believe that further development of small molecule CLIC3i are a promising new strategy for targeting metastatic breast cancer."

Metastases • Breast Cancer • Oncology • Solid Tumor • CLIC3 • TGM2

Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system. (PubMed, Int J Clin Pharm) - "This real-world study highlights high safety signals of interstitial lung disease associated with antibody-drug conjugates. Clinicians should be aware of these safety concerns and risk factors and implement early identification measures for their patients. Future research should prioritize comprehensively exploring the relationship between antibody-drug conjugates and lung diseases."

Adverse events • Journal • Real-world • Real-world evidence • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases

Enhancement of drug accessibility in lymph nodes to counteract organ-specific resistance to anti-CD22 immunotoxins (DGHO 2023) - "Mice were treated with Moxetumomab pasudotox (Moxe) or fluorochrome-labeled rIT... Despite similar sensitivity of lymphoma to Moxe in BM and SPL, responses strongly varied in LN, emphasizing the importance to study organ-specific tumor responses. Tumor clone-dependent resistance in LN correlated with reduced accessibility, which was reversed by combination with a rIT sensitizer. Currently, we evaluate whether this drug similarly enhances accessibility of full length and bispecific antibodies."

Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22

19-C-0042: Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either Rituximab (Rituxan(R)) or Ruxience for Relapsed Hairy Cell Leukemia (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Jun 2024 ➔ Jul 2023

Trial primary completion date • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

MEK-KINASE INHIBITOR (TRAMETINIB) AS A TREATMENT OPTION FOR HAIRY CELL LEUKEMIA (EHA 2023) - "In one case with a resistant/relapsing course of BRAFV600Eneg HCL (after 6 therapy lynes: splenectomy, IF-α + cladribine, 2 courses of cladribine with rituximab and with obinutuzumab, anti-CD22 immunotoxin moxetumomab pasudotox), trametinib monotherapy was started and allowed to achieve a good partial remission. Trametinib can be used as a preliminary stage in patients with HCL without BRAF mutation and as the main antitumor therapy in patients with resistant/recurrent HCL. At the same time, the drug is effective in the absence of the MAP2K1 mutation (unlike vemurafenib, which effective only in the presence of the BRAFV600E mutation), and, like vemurafenib, trametinib monotherapy can be effective at a reduced dose (1 mg/day or 1 mg every other day). Kinase inhibitor, Treatment, MEK, Hairy cell leukemia"

Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • BRAF • MAP2K1

Antibody-drug conjugate [ADC] treatment of leukaemia. (PubMed, Leuk Res) - "Three ADCs: Mylotarg, Besponda and Lumoxiti have improved overall survival and event=free survival as well as reduced relapse in 3 types of Leukaemia: AML, ALL and HCL, respectively. Lessons from these three SOC successful ADCs should guide other new ADCs in addressing the ADC-related off target toxicity due to the cytotoxic payload that limits their therapeutic index by using the successful approach of administrating lower doses in a fractionated regimen over time in separate days of the cycle to reduce the severity and frequency of the ADC-related serious toxicities that include ocular damage, long-term peripheral neuropathy and hepatic toxicity etc."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • Oncology • Pain

Single-agent rituximab as an effective salvage therapy in pre-treated hairy cell leukemia (ICML 2023) - "Single-agent rituximab can be a suitable treatment options in patients relapsing after repeated courses of purine analogs, if purine analogs are contraindicated (e.g., in case of poor bone marrow cellularity, high disease infiltration predicting long-lasting aplasia), especially if newer agents (such as moxetumomab or vemurafenib) are not easily available (as it happens in several countries). To our knowledge, this is the widest series of HCL patients receiving single-agent rituximab for disease relapse. Rituximab is an effective salvage therapy in pretreated HCL patients after failure of purine analogs, as it permits an adequate disease control with considerably long TTNT periods. It may be repeated if no alternatives are available, although it seems to reduce its efficacy in the following courses."

Hematological Malignancies • Lymphoma • Oncology • CD20

Moxetumomab-Rituximab to Eliminate Minimal Residual Disease in Hairy Cell Leukemia (PEGS 2023) - "Complete remissions in hairy cell leukemia (HCL) with anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox (Moxe) are more durable if minimal residual disease (MRD) negative, but anti-drug antibodies (ADA) can limit the effectiveness of the consolidation cycles needed to eliminate MRD. To prevent ADA, Rituximab or Ruxience was added to Moxe (MoxeR) and 9 (64%) of 14 evaluable patients so far achieved MRD-free CR. ADA was less frequent than Moxe alone historically."

Minimal residual disease • Residual disease • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Hairy Cell Leukemia: Where Are We in 2023? (PubMed, Curr Oncol Rep) - "Purine nucleoside analogs remain the cornerstone of treatment, and the addition of rituximab has deepened and prolonged responses in the upfront and relapsed setting...Future efforts will focus on identifying patients with high-risk disease who require intensified regimens. Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease."

IO biomarker • Journal • Review • Bone Marrow Transplantation • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology • Rare Diseases • Transplantation

PROXY: US Post-Marketing Safety Study of Moxetumomab Pasudotox-tdfk (LUMOXITI) (clinicaltrials.gov) - P=N/A | N=2 | Terminated | Sponsor: AstraZeneca | Recruiting ➔ Terminated; Study stopped due to lack of recruitment.

Trial termination • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Refractory and relapsed hairy-cell leukemia (HCL): Casting light on promising experimental drugs in clinical trials. (PubMed, Expert Opin Investig Drugs) - "Novel drugs will soon be available to assist standard therapy for HCL and HCLv among patients with suboptimal results following PNA treatment. In particular, the BRAF inhibitors vemurafenib and dabrafenib, with or without rituximab, have revolutionized treatment of patients with relapsed or refractory disease."

Journal • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Negative Minimal Residual Disease Associated with Extended Response to Moxetumomab Pasudotox in Patients with Relapsed/Refractory Hairy Cell Leukemia: Long-Term Follow-up of Bone Marrow Immunohistochemistry Analyses from a Phase 1 Study (ASH 2017) - P1; "Cladribine monotherapy and cladribine followed by rituximab eliminated IHC MRD in some newly diagnosed HCL patients (Sigal et. Based on the results of this retrospective analysis, together with observations made in the vemurafenib study, BICR IHC MRD− vs MRD+ status is associated with extended DOR and PFS in patients with r/r HCL treated with moxetumomab pasudotox. If this finding can be replicated in additional clinical studies, including the phase 3 pivotal study of moxetumomab pasudotox, IHC MRD determinations may be useful in evaluating the efficacy of therapies in the r/r HCL population."

P1 data • Residual disease • Retrospective data • Biosimilar • Leukemia • Non-Hodgkin’s Lymphoma

Zuma-25: A Phase 2 Study of Brexucabtagene Autoleucel (KTE-X19) Chimeric Antigen Receptor T-Cell Therapy in Adult Patients with Relapsed/Refractory Rare B-Cell Malignancies (TCT-ASTCT-CIBMTR 2023) - P2 | "Study Design and The study will use a basket study design spanning 4 single-armed substudies: R/R WM (n=60) after ≥2 prior lines of therapy that must have included a BTKi; R/R RT DLBCL variant (n=60) after 1 line of therapy; R/R BL (n=20) after 1 line of therapy; or R/R HCL (n=20) after ≥2 lines of therapy including at least one purine nucleoside analog and moxetumomab pasudotox (if available). Pts will not be eligible if they had received prior CAR T-cell or CD19-targeted therapy or have central nervous system disease. With the aim to potentially provide a new treatment option for pts with rare hematological malignancies that are associated with poor prognosis, this study will be open and enrolling pts at sites in North America and Europe (NCT05537766)."

CAR T-Cell Therapy • Clinical • P2 data • Acute Lymphocytic Leukemia • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • T Acute Lymphoblastic Leukemia • Waldenstrom Macroglobulinemia • CD4