Notably, 7b also showed efficacy against drug-resistant MM cell lines, including bortezomib- and lenalidomide-resistant cells. In vivo, 7b also exhibited remarkable anti-MM activity with tolerable side effects. In conclusion, targeting ClpP represents a promising therapeutic strategy for MM, with 7b serving as a potent anti-MM agent, especially for relapsed and refractory MM.

P2, N=41, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P3, N=623, Completed, The Lymphoma Academic Research Organisation | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Jan 2025

P=N/A, N=105, Completed, Celgene | Recruiting --> Completed | N=560 --> 105

P1, N=24, Completed, Novo Nordisk A/S | Active, not recruiting --> Completed | Trial completion date: May 2024 --> Sep 2024

P1/2, N=68, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

While lenalidomide-based immunotherapy remains the standard of care for relapsed iNHL, its frontline use is limited, due to nonsuperiority as compared to CIT...We also summarize the activity in iNHL of agents targeting antigens other than CD20 (including CD19 and CD79b), and novel immunotherapies and cellular therapies (including NK-cell based treatments). The therapeutic landscape of iNHL is soon to significantly change.

Resistant del(5q) MDS-L cells, as well as primary MDS marrow cells, are also sensitive to targeting of IGF-1R-related dependencies in del(5q) MDS, which include the Abl and MAPK signaling pathways. This work thus provides potential new therapeutic avenues for lenalidomide-resistant del(5q) MDS.

The response of disease to ruxolitinib may be transient and it may only serve as a temporary treatment prior to transplantation. The patient achieved complete hematologic remission and molecular response during the long-term follow-up; however, a complete molecular remission was not attained. The underlying mechanism of lenalidomide in these diseases necessitates further comprehensive investigation through fundamental research and clinical trials.

Tetrandrine suppressed CM cell growth by triggering G0/G1 cell cycle arrest via IL-6/CDC42 inhibition. Tetrandrine should be a promising compound for CM treatment.

P2, N=27, Terminated, Fondazione IRCCS Policlinico San Matteo di Pavia | N=40 --> 27 | Active, not recruiting --> Terminated; low patient enrollment rate

P2, N=38, Recruiting, The First Affiliated Hospital of Xiamen University | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Aug 2025 --> Aug 2027

P2/3, N=2310, Recruiting, CSL Behring | Trial completion date: Dec 2028 --> Aug 2029 | Trial primary completion date: Dec 2028 --> Aug 2029

P2/3, N=460, Active, not recruiting, University Health Network, Toronto | Suspended --> Active, not recruiting | Trial completion date: Dec 2026 --> Mar 2025 | Trial primary completion date: May 2026 --> Mar 2025

Resistant cell lines were established by exposing human B lymphoblast cell lines, MM.1S and MM.1R, to increasing doses of lenalidomide or pomalidomide. The inhibition of RAD51 combined with cisplatin therapy can maximize the treatment efficacy of MM patients resistant to dexamethasone and lenalidomide. Nevertheless, further research will be needed to explore the clinical applications of these findings.

In summary, this study in homogenously treated MDS patients with different abnormalities of 5q demonstrates the influence of cytogenetics on treatment results. Trial Registration: EudraCT number: 2011-001639-21; ClinicalTrials.gov identifier: NCT01556477.

In real-world, EPD is observed in more than one-fifth of patients, and it remains an unmet clinical need. Daratumumab-based therapies and ASCT significantly reduce the probability of EPD, while R2-ISS could serve as a useful prognostic tool for recognizing this population and guide therapeutic decisions.

Plerixafor was administered as a just-in-time approach with granulocyte-colony stimulating factor (G-CSF) alone or with cyclophosphamide (Cy) + G-CSF mobilization...There was no statistically significant difference between the two groups in terms of age, gender, RT history, previous lines of treatment, pretransplant lenalidomide cycles (p = 0.778, 0.165, 0.520, 0.094, 0.530, respectively)...This study demonstrates the comparable efficacy of generic plerixafor in myeloma patients, suggesting that it can be a cost-effective alternative with a similar safety profile. These findings contribute to the body of evidence on the use of generic plerixafor in specific patient cohorts, emphasizing its efficacy and safety for ASCT in a sole multiple myeloma patient cohort.

P3, N=675, Recruiting, Kodiak Sciences Inc | Trial completion date: Jan 2026 --> Apr 2027 | Trial primary completion date: Jan 2026 --> Apr 2026

In this study, we investigated the effects of pomalidomide, an immunomodulatory imide drug that induces the degradation of Ikaros and Aiolos, on HIV latency reversal and death of infected cells. Using CD4+ T cells from people living with HIV on suppressive antiretroviral therapy, as well as an in vitro model of productive HIV infection, we found that pomalidomide induced T cell activation and expression of stress proteins but no evidence of latency reversal or selective death of infected cells.

Transdermal administration of Len-NBHs represents a promising adjuvant therapy for the treatment of malignant melanoma. Preoperative administration of Len-NBHs can inhibit the outward spread of melanoma, reduce tumor size, thereby decreasing the surgical excision area and improving patient survival rates and prognosis.

P1, N=6, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: May 2027 --> Nov 2027 | Trial primary completion date: May 2027 --> Nov 2026

P1, N=6, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> May 2027 | Trial primary completion date: Jan 2025 --> May 2027

Conversely, inhibition of VLCFA degradation via suppression of peroxisomal acyl-CoA oxidase 1 (ACOX1) increased the cytotoxicity of bortezomib, its next-generation analog, carfilzomib, and the immunomodulatory agent lenalidomide. Mechanistically, inhibition of ACOX1 promoted the accumulation of VLCFA-containing cerebrosides, altered MET and IGF1R interaction with a cerebroside analog, and selectively inhibited the association of these kinases with the plasma membrane signaling platforms, importantly, without disrupting the platforms' integrity. Our study revealed a specific metabolic vulnerability of MM cells and identified a targetable axis linking VLCFA metabolism to the regulation of MET and IGF1R activity.

P2, N=44, Completed, International Extranodal Lymphoma Study Group (IELSG) | Active, not recruiting --> Completed | Trial completion date: Nov 2029 --> Dec 2024

This study provides a possible strategy for a combination treatment with MLN4924 and Len for leukemia.

P1, N=32, Recruiting, argenx

P2, N=30, Recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

P2, N=46, Completed, University Hospital, Toulouse | Unknown status --> Completed

P=N/A, N=90, Recruiting, Children's Hospital, Zhejiang University School of Medicine; Children's Hospital, Zhejiang University School of Medicine | Not yet recruiting --> Recruiting

P4, N=60, Completed, Shandong Cancer Hospital; Shandong Cancer Hospital | Recruiting --> Completed

P2/3, N=460, Suspended, University Health Network, Toronto | N=1000 --> 460 | Recruiting --> Suspended

P3, N=180, Active, not recruiting, University of Chicago | Trial primary completion date: Nov 2024 --> Nov 2025

Previous data suggests almost one third of myeloma patients acquire mutations in the key IMiD effector cereblon by the time they are pomalidomide refractory. Dynamic modelling based on a newly generated crystal structure of the DDB1/CRBN/lenalidomide complex, with greater resolution than those published to date, helped to understand the impact of these mutations. These results have important implications for the interpretation of CRBN sequencing results from patients for future therapy decisions, particularly differentiating those who may, despite relapsing on IMiDs with CRBN mutations, have the potential to still benefit from the use of CELMoD agents.

Our findings suggest potential mechanisms of action for 22 pyroptosis-related genes in osteosarcoma and preliminarily predicted that the occurrence of osteosarcoma is closely related to pyroptosis, apoptosis, and immune regulation. Predicted Triethyl phosphate, Plinabulin, Siltuximab as potential osteosarcoma treatments.

We conducted the first trial of immunotherapy rituximab plus lenalidomide in newly diagnosed FL in China (NCT03715309). Collectively, PU.1 is essential in immunomodulatory effect of FL through PD-1/PD-L1- and 4-1BB/4-1BBL-mediated microenvironmental modulation. Dual targeting PD-L1 and 4-1BB could be an alternative immunotherapeutic strategy in the chemo-free era of FL treatment.

P=N/A, N=30, Shanghai General Hospital; Shanghai General Hospital

P4, N=40, HenanCancerHospital; He'nan Cancer Hospital

Here, we report a comprehensive NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients...Moreover, large M-CH clones showed longer time to hematologic recovery after ASCT compared to the remaining cohort (p=0.026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in MCL patients.

P1, N=85, Completed, Hoffmann-La Roche

In vivo, SH514 effectively inhibited the proliferation of MM tumors, showing much better antitumor efficacy than the clinical drug lenalidomide, and exhibited no significant toxicity. Thus, these IRF4 inhibitors could serve as promising leads for the development of novel anti-multiple myeloma agents.

P2, N=81, Recruiting, Tourmaline Bio, Inc. | Trial completion date: Feb 2026 --> Nov 2026 | Trial primary completion date: Feb 2025 --> Nov 2025