Waldenstrom Macroglobulinemia

P2, N=47, Completed, Beijing InnoCare Pharma Tech Co., Ltd. | Active, not recruiting --> Completed

P2/3, N=422, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-naïve and relapsed/refractory patients (94% for all patients, 95% for treatment-naïve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% )...It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors' and patients' understanding of WM is one of the most urgent issues that must be addressed right now.

The covalently bound Ibrutinib molecule, recognized for its ability to inhibit BTK, was used as the query molecule...Covalent docking simulations were applied to the selected small-molecules obtained through text mining from databases. Potent hit molecules capable of inhibiting BTKs through virtual screening algorithms were identified, paving the way for novel therapeutic strategies in the treatment of CLL.

P2, N=90, Recruiting, Kite, A Gilead Company | Trial completion date: Dec 2027 --> Mar 2025 | Trial primary completion date: Dec 2027 --> Mar 2025

P2, N=92, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Mar 2028 | Trial primary completion date: Apr 2024 --> Mar 2028

P2, N=31, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2022 --> Aug 2023

P1/2, N=466, Recruiting, BeiGene | N=291 --> 466

P1, N=120, Recruiting, Stanford University | Not yet recruiting --> Recruiting

P1, N=120, Not yet recruiting, Stanford University

The findings of the RAINBOW trial (NCT046152), comparing the dexamethasone, rituximab, and cyclophosphamide (DRC) regimen to the first-generation, ibrutinib are awaited, but more studies are needed to draw definitive conclusions on the comparative efficacy of chemoimmunotherapy and BTKi. Complete response is elusive with BTKi, and combination regimens to improve upon the efficacy and limit the treatment duration are also under evaluation in WM.

P1/2, N=860, Active, not recruiting, Loxo Oncology, Inc. | Trial completion date: Apr 2024 --> Jan 2028 | Trial primary completion date: Apr 2024 --> Sep 2027

P1, N=150, Recruiting, Nkarta Inc. | Trial primary completion date: Dec 2023 --> Aug 2024

P1, N=3, Terminated, Jorge J. Castillo, MD | Recruiting --> Terminated; Lack of efficacy

P1/2, N=69, Recruiting, Barbara Ann Karmanos Cancer Institute | Phase classification: P1b/2 --> P1/2 | N=44 --> 69 | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=0, Withdrawn, Michael A. Thompson, MD, PhD | N=10000 --> 0 | Enrolling by invitation --> Withdrawn

P1, N=48, Recruiting, Emory University | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P1/2, N=190, Active, not recruiting, ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

No abstract available

The patient received 6 cycles of rituximab and bendamustine treatment, and no residual marrow involvement was found on the follow-up bone marrow biopsy. CONCLUSIONS We report a non-IgM LPL case featuring no light chain production and no heavy chain secretion, which we believe is the first reported case of this kind in the literature.

Taken together, our results indicated that ST2825 leads to ROS-dependent apoptosis in MM cells and could be an attractive therapeutic candidate for patients with MM. By highlighting the pathological mechanism of MyD88 in MM, this study also provides novel treatment strategies to conquer MM.

Here, we show that KIN-8194, a dual inhibitor of BTK and HCK with in vivo activity against Myd88-L265P-driven diffuse large B-cell lymphoma and Waldenström Macroglobulinemia, has a potent growth inhibitory effect in MCL cell lines and primary MCL cells, irrespective of their sensitivity to BTKi (ibrutinib and acalabrutinib). Taken together, our data demonstrate that KIN-8194 inhibits growth and integrin-mediated adhesion of BTKi-sensitive MCL cells, as well as MCL cells with primary or acquired BTKi resistance. This renders KIN-8194 a promising novel treatment for MCL patients.

Our study concludes that serum CXCL13 levels decrease in WM patients treated with various regimens and correlate with treatment response. Detecting serum CXCL13 at baseline or after treatment help in predicting prognosis.

Extensive workup excluded other diagnostic possibilities, including the presence of Donath-Landsteiner antibodies and cryoglobulins. Successful treatment with CyBorD (cyclophosphamide, bortezomib and dexamethasone) achieved complete remission, and additional RBC transfusions using warmers were completed uneventfully.

Finally, gene expression analysis showed common transcriptional features between patients compared to the healthy control but also differentially expressed genes between MYD88 L265P and MYD88 WT patients involved in distinct pathways, including NFκΒ, BCL2, and BTK. Overall, our data highlight the intra-tumor clonal heterogeneity in WM with potential prognostic and therapeutic implications.

P1, N=30, Active, not recruiting, Boryung Pharmaceutical Co., Ltd | Recruiting --> Active, not recruiting

Our data demonstrate that PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay is a fast, highly sensitive, and specific method for the detection of MYD88 L265P compared with conventional AS-PCR.

P1, N=30, Recruiting, Bio-Path Holdings, Inc. | Trial completion date: Jan 2025 --> Jan 2026

P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P2, N=92, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P=N/A, N=656, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

In conclusion, our findings shed light on the unique molecular complexity of PBL, unveiling its mutational landscape and potential therapeutic targets. Due to the rarity of PBL, further research with a more extensive sample size is essential to completely elucidate the mutational landscape of PBL.

P1/2, N=161, Active, not recruiting, Acerta Pharma BV | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2025 --> Apr 2026

P1, N=37, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=48, Active, not recruiting, Kami Maddocks, MD | Trial completion date: Dec 2023 --> Dec 2024

NGS performance for the MYD88L265P variant was 96% when compared to qPCR. In conclusion, targeted NGS provided important diagnostic and prognostic information in a routine clinical setting.

P=N/A, N=592, Completed, University Hospital Southampton NHS Foundation Trust | Active, not recruiting --> Completed

In TP53MUT, compared to ibrutinib, zanubrutinib-treated patients had higher VGPR+CR (34.6% vs 13.6%, P<0.05), numerically improved MRR (80.8% vs 63.6%, P=0.11), and longer PFS (not reached vs 44.2 months, HR=0.66, P=0.37). Collectively, WM patients with CXCR4MUT or TP53MUT had worse prognosis compared to patients with WT alleles and zanubrutinib led to better clinical outcomes.

P1, N=110, Recruiting, Carna Biosciences, Inc. | Phase classification: P1b --> P1

P=N/A, N=30, Not yet recruiting, British Columbia Cancer Agency

P1, N=18, Active, not recruiting, Calibr, a division of Scripps Research | N=36 --> 18 | Trial primary completion date: Aug 2023 --> Apr 2024