pomalidomide / Generic mfg. - LARVOL DELTA

Relapse of Multiple Myeloma Presenting as a Sellar Mass (ENDO 2025) - "The clinical picture was most concerning for CNS relapse of the patient's myeloma; he received five fractions of radiation therapy to the right cavernous sinus, and was started on venetoclax, pomalidomide, and dexamethasone with plans to add carfilzomib in the future. Plasma cell tumors should be considered in the differential for lesions involving the sella, particularly in the presence of cranial nerve palsies. (1) DiDomenico J, Ampie L, Choy W, Lamano JB, Oyon DE, Kesavabhotla K, Bloch O. Sellar plasmacytomas masquerading as pituitary adenomas: A systematic review. J Clin Neurosci."

Bone Marrow Transplantation • Endocrine Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Pituitary Gland Carcinoma • Plasmacytoma • CD20 • SDC1 • SYP

Preclinical development of TQB3019: A potent and selective oral BTK degrader leveraging the OAPD® platform to overcome acquired resistance mutations (AACR 2025) - "Unlike covalent inhibitor ibrutinib, TQB3019 also demonstrated improved selectivity for BTK over TEC. TQB3019 using a novel designed CRBN ligand showed over 14-fold higher binding affinity to CRBN protein compared to pomalidomide... Developed using Chia Tai Tianqing's OAPD® platform, TQB3019 is an orally available BTK degrader with promising potency, superior selectivity, and favorable pharmacological properties. With IND (Investigational New Drug) application forthcoming, TQB3019 represents a promising therapeutic candidate to address resistance challenges associated with traditional BTK inhibitors."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lung Cancer • Oncology • Solid Tumor • CRBN • EGFR • IKZF1

Autophagy disruption via PIKfyve inhibition as a novel strategy to enhance immunotherapy responses in multiple myeloma (AACR 2025) - "In addition to its robust single agent anti-MM activity, PIK001 presented synergistic activity with relevant anti-MM therapeutics, including selinexor, venetoclax, and pomalidomide (IMiDs), in vitro. This hypothesis aligns with recent studies demonstrating increased tumor-specific MHC Class I expression and improved cancer immunotherapy efficacy following PIKfyve inhibition in solid tumors. Together, these results highlight the potential of PIKfyve inhibitors to synergize with existing anti-MM therapeutics and sensitize MM cells to MHC-dependent immunotherapies via autophagy disruption."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • MYC • SDC1

A phenotypic screening method identifies a potent anti-cancer PROTAC targeting MAP3K1 (AACR 2025) - "The identification of Thalidomide, Lenalidomide, and Pomalidomide as Cereblon (CRBN) binders spurred the development of proteolysis-targeting chimeras (PROTACs). Furthermore, A Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) screen of 50-008 across ~900 cancer cell lines identified 267 sensitive cancer cell lines (IC50 10 μM). Mechanistic studies in T47D cells demonstrated that 50-008 degrades MAP3K1 and modulates the activation of key downstream effectors, such as ERK and IKKβ."

Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • CRBN • DDB1 • MAP3K1

The immunomodulatory effects of daratumumab-based therapy on functional high-risk relapse/refractory multiple myeloma (fHRMM) patients enrolled in the MyDRUG trial (AACR 2025) - P1/2 | "Background: The goal of this study is to evaluate the immunomodulatory effects of daratumumab-(anti-CD38)-based therapy on fHRMM patients enrolled in the MMRF sponsored MyDRUG umbrella clinical trial (NCT03732703) over the duration of therapy and to correlate immune changes with patient response. fHRMM who had received 1-3 prior therapies (exposed to at least one proteasome inhibitor and an IMiD) were given a combination of daratumumab (D), ixazomib (I), pomalidomide (P) and dexamethasone (d) (D-IPd) quadruplet therapy. Paired single cell RNA and TCR sequencing of BM T cells from RRMM patients receiving D-IPd quadruplet therapy revealed a selective expansion of clonotypic CD8+ T cells with a clonal replacement of BM exhausted clonotypes by dysfunctional circulating CD8+ T cells in responders over time."

Clinical • Immunomodulating • Hematological Malignancies • Multiple Myeloma • Oncology • CD8 • SDC1

mRNA-based restoration of pomalidomide sensitivity in multiple myeloma (AACR 2025) - "This peptide is being validated for BCMA binding, and will be conjugated with the nanoparticle-coated CRBN mRNA for targeted delivery to the malignant plasma cells. Findings from this work will advance mRNA-based therapeutics for overcoming drug resistance caused by genetic alterations in target proteins."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN

Isa-Pom-Dex in Elderly/Frail Subjects With RRMM (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Suspended ➔ Active, not recruiting | Trial completion date: Mar 2031 ➔ Mar 2028 | Trial primary completion date: Dec 2028 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Geriatric Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Proteolysis-targeting vaccines for robust combination immunotherapy of melanoma (AACR 2025) - "By co-delivering PROTAVs with a bi-adjuvant system through lipid nanoparticles (LNPs), we aim to significantly improve the quantity and quality of specific CD8+ T cells, thereby enhancing the efficacy of ICB-based combination therapies. Ovalbumin (OVA) was employed as a model antigen, with pomalidomide serving as the E3 ligase ligand, conjugated via a series of linkers... PROTAVs effectively elicit robust CD8+ T cell responses and alleviate tumor immunosuppression, enhancing the efficacy of ICB combination immunotherapy for melanoma. These findings highlight the potential of PROTAVs as a versatile platform for developing cancer therapeutic vaccines, offering broad applicability for robust immunotherapy across various cancer types."

Melanoma • Oncology • Solid Tumor • CD8

HP-001: A highly potent IKZF1/3 degrader that demonstrates superior safety profile (AACR 2025) - "IMiDs (e.g. pomalidomide, CC-220, CC-92480. HP-001 is a highly potent, catalytic degrader of IKZF1/3, with marked antitumor activity as a single agent and in combination with dexamethasone. HP-001 is currently in phase 1 clinical trial (CDE registration number: CTR20242943), a first-in-human, open-label, multicenter study to evaluate it as monotherapy in patients with r/r MM or NHL."

Clinical • Late-breaking abstract • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN • GSPT1 • IKZF1 • SALL4

Discovery of novel, potent and orally active GSPT1 molecular glue degraders (AACR 2025) - "In fact, clinical proof of concept has been obtained with immunomodulatory drugs such as thalidomide, lenalidomide and pomalidomide, which degrade IKZF1/IKZF3...GSPT1 degrader antibody conjugates are now in clinical trials for breast cancer (ORM-5029) and AML (BMS-986497/ORM-6151)...These encouraging results have prompted us to explore a series of GSPT1 MGDs.In the present study, we describe the discovery of a series of novel, potent and orally active GSPT1 MGD targeting tumors with high GSPT1 expression...This compound demonstrates in vivo efficacy in CDX model with a favorable profile comparable to that of MRT-2359. In summary, a series of orally active GSPT1 degraders have been discovered with preclinical profile suitable for further development to manage cancers with high GSPT1 expression."

Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL6 • GSPT1 • IKZF1 • IKZF3 • STAT6 • VAV1

Bristol Myers Squibb Reports First Quarter Financial Results for 2025 (Bristol-Myers Squibb) - "Legacy Portfolio revenues of $5.6 billion declined 20% on a reported basis and Ex-FX. The decline was driven by continued generic impact on Revlimid, Pomalyst, Sprycel and Abraxane, as well as the impacts from U.S. Medicare Part D redesign."

Commercial • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Indolent Lymphoma • Kaposi Sarcoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Pancreatic Cancer • Thoracic Cancer • Triple Negative Breast Cancer

Updated results from phase 2b study of selinexor in combination with carfilzomib, daratumumab, or pomalidomide in patients with multiple myeloma (MM) relapsing on current therapy. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04661137 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Combination therapy • P2b data • Hematological Malignancies • Multiple Myeloma • Oncology

Minimal residual disease (MRD) negativity (neg) in patients (pts) with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd): Analysis from the DREAMM-8 trial. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT04484623 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Minimal residual disease • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology

DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM): A subgroup analysis in patients with high-risk cytogenetic features. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT04484623 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Isatuximab (Isa) subcutaneous (SC) via an on-body delivery system (OBDS) vs Isa intravenous (IV), plus pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma (RRMM): Results of the randomized, non-inferiority, phase 3 IRAKLIA study. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT05405166 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Head-to-Head • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

AlloRelapseMM: Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy (clinicaltrials.gov) - P3 | N=28 | Terminated | Sponsor: Universitätsklinikum Hamburg-Eppendorf | N=482 ➔ 28 | Trial completion date: Mar 2033 ➔ Mar 2025 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2028 ➔ Mar 2025; The reason for the end of recruitment is that the recruitment target could not be achieved despite all efforts and the G-BA (financing party) does not consider a continuation of the AlloRelapseMM study to be expedient.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study (clinicaltrials.gov) - P4 | N=12 | Completed | Sponsor: Amsterdam UMC, location VUmc | Not yet recruiting ➔ Completed

Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Discovery of a novel molecular glue degrader targeting GSPT1/2 with a non-IMiD-based CRBN binder. (PubMed, Eur J Med Chem) - "Treatment with 4a demonstrated significant anti-proliferative activity across multiple cell lines, which was diminished by co-treatment with MLN4924, suggesting the involvement of the Cullin-containing complex...BRET assays and competition assays with pomalidomide demonstrated that 4a binds to the C-terminal IMiD binding site of CRBN, leading to the degradation of GSPT1. Despite lacking the characteristic glutarimide moiety present in other CRBN-based molecular glue degraders, 4a interacts effectively with the IMiD binding site of CRBN. Structural characterization through analog synthesis further underscored the importance of specific structural features for CRBN engagement, GSPT1/2 degradation, and anti-proliferative effects, establishing 4a as a promising novel GSPT1/2 degrader with significant therapeutic potential."

Journal • Targeted Protein Degradation • CRBN • GSPT1

An oncolytic adenovirus targeting SLAMF7 demonstrates anti-myeloma efficacy. (PubMed, Leukemia) - "Combination therapy with anti-myeloma drugs, bortezomib, melphalan, panobinostat and pomalidomide, enhanced Ad[CE1A] efficacy, with melphalan upregulating SLAMF7, resulting in increased viral replication. In summary, these findings support Ad[CE1A] as a promising myeloma therapy."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • CALR • HLA-C • SLAMF7

Exploring the symptom experience of patients taking oral anticancer medications for multiple myeloma: A qualitative, descriptive study (ONS 2025) - "Patients were taking either lenalidomide (n=13, 76.5%) or pomalidomide (n=4, 23.5%). Symptoms varied and may be attributed to disease and/or medication side effects. Future research should further quantify the prospective symptom experience of patients taking OAMs for multiple myeloma to better support patient adherence to OAM therapy for multiple myeloma."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Oral Cancer

Effectiveness of Bridging Therapy Corresponds to Improved Outcomes After Receiving CAR-T Therapy: Phase 3 CARTITUDE-4 Study of Patients With Relapsed, Lenalidomide-Refractory Multiple Myeloma (ONS 2025) - P3 | "Bridging therapy included physician's choice of either daratumumab, pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd). Of 176 patients who received cilta-cel as study treatment, 158 received DPd and 18 received PVd as bridging therapy. Most patients had ≥25% reduction in tumor burden in response to bridging therapy (Figure). At the 15.9-month median follow-up, median PFS (95% confidence interval) was not reached (not estimable [NE]-NE) in the ≥25% decrease group and 19.2 months (15.8 months-NE) in the <25% decrease group."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Incidence of Infection and Immune Recovery in the CARTITUDE-4 Trial of Ciltacabtagene Autoleucel Versus Standard of Care for Treatment of Multiple Myeloma (ONS 2025) - P3 | "Significance & Background: Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival versus standard of care (SOC; hazard ratio [HR], 0.26; P<0.0001) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy in the phase 3 CARTITUDE-4 trial (NCT04181827) at the 15.9-month median follow-up (MFU)...Interventions: Patients were randomized to a single infusion of cilta-cel or SOC (daratumumab-pomalidomide-dexamethasone/pomalidomide-bortezomib-dexamethasone)... Overall, 128 of 208 cilta-cel–treated patients (61.5%) and 157 of 208 SOC-treated patients (75.5%) had treatment-emergent (TE) infections of any grade; grade ≥3 TE infections occurred in 57 patients (27.4%) and 56 patients (26.9%) in the cilta-cel versus SOC groups, respectively. Rates of grade ≥3 TE infections in the cilta-cel group were highest within the first 6 months and decreased thereafter (Figure). TE fatal infections occurred in 9..."

Hematological Malignancies • Multiple Myeloma • Oncology

Long-term Efficacy and Safety of Ciltacabtagene Autoleucel Versus Standard of Care for Treatment of Lenalidomide-Refractory Multiple Myeloma in the CARTITUDE-4 Trial (ONS 2025) - P3 | "Interventions: Patients in CARTITUDE-4 were randomly assigned to a single infusion of cilta-cel or SOC (pomalidomide-bortezomib-dexamethasone [PVd]/daratumumab-pomalidomide-dexamethasone [DPd]). Overall, 419 patients were randomized (intent-to-treat population; cilta-cel, n=208; SOC, n=211). Median OS was not reached (NR) with cilta-cel or SOC (HR, 0.55 [protocol-specified weighted analysis]; 95% confidence interval, 0.39-0.79; P=0.0009); 30-month OS rates were 76% and 64%, respectively (Table). OS benefit was generally maintained across prespecified subgroups (eg, 1 vs 2-3 prior lines of therapy, cytogenetic high-risk disease, refractory status)."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

A scientometric study on research characteristics and trends of amyloidosis involving the oral cavity. (PubMed, J Dent Sci) - "The trend of drug aspect, e.g. prednisone, colchicine, corticosteroid, doxorubicin, and vincristine before 2015 has changed to monoclonal antibody, daratumumab, tafamidis, proteasome inhibitor, carfilzomib, ixazomib, patisiran, pomalidomide, diflunisal, and doxycycline. Herein, we highlight the awareness of early diagnosis and improve the access to care for amyloidosis, since oral involvement frequently constitutes the first sign of this disease. This scientometric study elucidated the current scenario and research trends of amyloidosis, underpinning that stomatologists can play roles in providing early recognition and timely diagnosis of amyloidosis when it involved the oral cavity."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Oncology

New therapies in multiple myeloma: benefits and limitations. (PubMed, Pol Arch Intern Med) - "Over the last 20 years, there has been a dramatic increase in the availability of new therapies for patients with MM with a significant improvement in remission duration and overall survival: the introduction of immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), monoclonal antibodies (eg, daratumumab), and proteasome inhibitors (bortezomib, karflizomib) into the treatment paradigm has meaningful and favorably changed the prognosis for MM patients. More recently, the development of molecular targeted therapies, especially bispecific antibodies and chimeric antigen receptor (CAR)-T cells as part of immunotherapy has rapidly evolved into their use as part of clinical practice. This review provides an overview of emerging molecularly targeted therapies for MM, highlighting bispecific antibodies and CAR T-cell approaches, and examining key structural and functional considerations, principal findings from current clinical trials, and strategies for managing..."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology