Entity's Board Research Articles

Hydroxyurea Dose Optimization Is Safe and Improves Outcomes for Children with Sickle Cell Anemia Living in Sub-Saharan Africa: The Reach Experience

Disclosures Introduction: Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) is an open-label multi-country prospective trial of hydroxyurea for children with sickle cell anemia (SCA) in sub-Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). Initial results documented the feasibility, safety, and benefits of hydroxyurea treatment with dose escalation to maximum tolerated dose (MTD), but further hydroxyurea dose optimization data are needed to assess long-term benefits and risks. We now report the REACH experience with up to 8 years of hydroxyurea treatment, describing laboratory responses, clinical outcomes, and dose-related toxicities (DLT). Methods: Children 1-10 years of age with SCA were enrolled. After screening, the hydroxyurea dose was fixed at 15-20 mg/kg/day for 6 months with monthly complete blood counts (CBC) to ensure safety. From Month 6-24, the dose was escalated (5 mg/kg every 8 weeks) to MTD, defined as mild myelosuppression with absolute neutrophil count (ANC) <4.0 x 109/L on 2 consecutive CBC. Beyond Month 24, dosing was optimized for weight gain and increased based on CBC results. With a low DLT rate using the original MTD criteria (ANC <1.0 x 109/L, Hb <4.0 g/dL, reticulocyte count <80 x 109/L unless Hb >7.0 g/dL, or platelets <80 x 109/L), dose optimization criteria were modified toward a target ANC of 3.0 x 109/L. The hydroxyurea dose was increased if ANC >3.0 x 109/L, Hb >5.0 g/dL, reticulocytes >100 x 109/L and platelets >100 x 109/L. Laboratory responses, clinical responses, and DLT rates were compared across the four dosing phases (Screening, Fixed Dose, Dose Escalation, and Dose Optimization). Results: A total of 635 children enrolled in REACH and began screening; 606 initiated hydroxyurea and currently 527 (87%) remain in the trial, with an average treatment duration of 83 months (range 76-105 months) and total of 4,199 patient-years of hydroxyurea treatment. Over 85% achieved MTD initially at an average hydroxyurea dose of 22.5 ± 5.0 mg/kg/day, ranging from 19.0 mg/kg/day in Angola to 25.4 mg/kg/day in Uganda. With dose optimization, doses have increased and the most recent average is 28.1 ± 5.1 mg/kg/day, ranging from 27.1 mg/kg/day in Congo to 28.8 mg/kg/day in Uganda. Across the four dosing phases, key laboratory responses (Hb, HbF, and ANC) have improved over time: the average Hb increased from 7.3 g/dL at baseline to 8.4 g/dL at MTD and is currently 8.7 g/dL; average HbF increased from 11% at baseline to 25% at MTD and is now 27%; and average ANC decreased from 6.8 x 109/L at baseline to 4.2 x 109/L at MTD and is currently 3.6 x 109/L. Comparing event rates per 100 patient-years between Screening to Dose Optimization, vaso-occlusive episodes decreased from 104.5 to 43.9, acute chest syndrome decreased from 9.0 to 2.1, splenic sequestration decreased from 1.8 to 0.7 and stroke decreased from 1.8 to 0.3. Transfusion rates decreased from 48.6 to 11.2, malaria from 46.8 to 19.1, non-malarial infections from 111.7 to 52.9, and death has decreased from 3.6 to 1.0 per 100 pt-years. As a composite, all sickle-related clinical events including vaso-occlusive pain, acute chest syndrome, stroke, and all serious adverse events have decreased as the dose increased (Fig 1). Lab toxicities have been infrequent and transient, with 2/3 identified incidentally during a scheduled visit without illness. Among 25,730 total CBCs obtained in REACH, only 421 (2.6%) in 225 participants had a DLT, and the incidence rate has not increased across dosing phases from Screening (0.22 events per pt-year) through Dose Optimization (0.21 events per pt-year). During COVID, 549 children had labs checked at 6-month intervals without any increase in the DLT rate or clinical events. Many DLT are unrelated to hydroxyurea including thrombocytopenia (33%) with splenomegaly, followed by anemia (26%) with malaria. Severe neutropenia (ANC <0.5 x 109/L) was very rare (5 events) with no neutropenic infections. Conclusions: Hydroxyurea is safe, well-tolerated, and effective for children in REACH. Hydroxyurea escalation to MTD with further dose optimization is associated with improved laboratory and clinical responses, but no increased toxicity. Routine CBC monitoring at 3-month intervals is sufficient and extension to longer intervals may be appropriate. Hydroxyurea dosing at 25-30 mg/kg/day is feasible and safe in sub-Saharan Africa and provides optimal treatment benefits. Aygun: GBT: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Latham:Emmaus Medical: Research Funding. Ware:Addmedica: Research Funding; Emmaus Medical: Research Funding. Figure 1

Synthetic Introns Identify the Novel RNA Splicing Factor GPATCH8 As Required for Mis-Splicing Induced By SF3B1 Mutations

Disclosures Mutations in the core RNA splicing factor SF3B1 are common across MDS, CLL, and clonal hematopoiesis. Prior studies have elucidated that mutations in SF3B1 result in neomorphic widespread changes in splicing due to usage of aberrant intronic branchpoint nucleotides. However, the molecular basis by which mutant SF3B1 induces mis-splicing is not established and therapeutic means to correct mis-splicing due to mutant SF3B1 do not exist. Recently, the aberrant gain-of-function splicing activity of mutant SF3B1 was harnessed to regulate expression of proteins in a mutant selective manner using synthetic version of endogenous mRNA sequences uniquely recognized by mutant SF3B1. Here, we utilized this technology to engineer a synthetic intron derived from MAP3K7 that interrupts the coding sequence of the fluorescent protein mEmerald such that mutant SF3B1 produces lower mEmerald expression than SF3B1 wild-type (WT) cells (Fig.A). This fluorescent splicing reporter was then used to perform positive enrichment whole genome CRISPR screens to identify genes whose deletion corrects SF3B1 mutant aberrant splicing. GPATCH8 was the single most robust hit. GPATCH8 knockout strongly corrected mis-splicing of both synthetic and endogenous MAP3K7 introns (Fig.A). A previously unexplored protein, GPATCH8 has domains characteristic of RNA splicing factors including a G-patch motif, thought to be important in activating RNA helicases. Interestingly, recent work suggests that mutations in SF3B1 result in mis-splicing by disrupting physical interaction of SF3B1 to the RNA helicase DHX15 via the G-patch domain containing protein SUGP1. We therefore compared SUGP1 to GPATCH8 activity, evaluating first their transcriptome-wide binding sites using TRIBE-seq. We found that both proteins predominantly target intronic sequences over other genomic regions suggesting roles in splicing. RNA-seq of SF3B1 mutant and WT cells with or without GPATCH8/SUGP1 deletion revealed that ~33% of SF3B1 mutant splicing alterations are corrected by GPATCH8 deletion, while ~60% of SF3B1 mutant splicing alterations are recapitulated upon SUGP1 deletion. GPATCH8 regulated splicing events have stronger branchpoints indicating a potential role for GPATCH8 in 3' splice site recognition. To further understand the connection between GPATCH8 and mutant SF3B1, we performed mass spectrometry studies of immunoprecipitated endogenous GPATCH8 in SF3B1 WT and mutant knockin cells. This revealed strong interaction between GPATCH8 and DHX15. GPATCH8 interacts with DHX15 at the same sites previously shown to be occupied by SUGP1 in crystal structures of the SUGP1/DHX15 interaction. These data and further biochemical studies elucidated that GPATCH8 competes with SUGP1 for interaction to DHX15. As such, deletion of GPATCH8 corrects SF3B1 mutant mis-splicing by enhancing the interaction of SUGP1 and DHX15 to the mutant SF3b complex. Given that GPATCH8 is required for a large proportion of the splicing alterations induced by mutant SF3B1, we next evaluated the phenotypic effect of correcting SF3B1 mutant mis-splicing. We first tested the impact of anti-Gpatch8 shRNAs in bone marrow from WT mice as well as animals with conditional knockin of Sf3b1 K700E, K666N, or R625H mutations. While each Sf3b1 mutation results in impaired colony formation of hematopoietic precursors in methylcellulose assays, silencing of Gpatch8 rescued colony formation from hematopoietic precursors of each of the different Sf3b1 mutant mice and was tolerated by normal hematopoietic precursors (Fig.B). Moreover, while CRISPR base-edited knockin of the SF3B1 K700E mutation in adult CD34 + cells impaired erythroid development, this erythroid differentiation defect was rescued by GPATCH8 deletion in the same cells (Fig.B). These data identify GPATCH8 as a novel RNA splicing factor involved in quality control of RNA branchpoint selection whose expression is required for mis-splicing by the different mutant forms of SF3B1. GPATCH8 antagonizes the activity of SUGP1 by competing for interaction with DHX15. These findings suggest that disrupting GPATCH8/DHX15 interaction could have important therapeutic benefit for the multitude of SF3B1 mutant hematopoietic diseases. This study also demonstrates the power of synthetic intronic splicing assays for discovery of trans factors and druggable proteins required by leukemia-associated mutant RNA splicing factors. Abdel-Wahab: AbbVie, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Loxo/Lilly: Consultancy; Nurix Therapeutics: Research Funding; Minovia Therapeutics: Research Funding; Amphista Therapeutics: Consultancy; AstraZeneca: Consultancy; Harmonic Discovery: Current holder of stock options in a privately-held company. Figure 1

The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

Tisagenlecleucel Vs Standard of Care As Second-Line Therapy of Primary Refractory or Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma: Analysis of the Phase III Belinda Study

Tisagenlecleucel Vs Standard of Care As Second-Line Therapy of Primary Refractory or Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma: Analysis of the Phase III Belinda Study

Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B without Inhibitors (ATLAS-A/B)

Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B without Inhibitors (ATLAS-A/B)

The Longitudinal Dynamics and Natural History of Clonal Hematopoiesis

Human cells acquire somatic mutations throughout life, some of which can drive clonal expansion. Such expansions are frequent in the hematopoietic system of healthy individuals and have been termed clonal hematopoiesis (CH). While CH predisposes to myeloid neoplasia and some non-hematological diseases, we have limited understanding of how and when CH develops, what factors govern its behavior, how it interacts with aging and how these variables relate to malignant progression.To address these questions, we adopted the experimental approach outlined in Figure 1. We began by analyzing 1,593 blood DNA samples from 385 elderly individuals, each sampled up to 5 times over ~13 years. We used deep targeted sequencing to identify and track 697 CH clones over this period. We constructed a logistic regression model and found that the great majority of clones (92.4%) expanded at a stable exponential rate during old age, enabling accurate prediction of future clonal growth (mean absolute error of measured vs predicted clone size: 3.5%). Different mutations drove substantially different growth rates, with mutations in DNMT3A and TP53 displaying the slowest average annual growth rates of ~5%. Clones with mutations in the other common driver genes (TET2, ASXL1, PPM1D and SF3B1), expanded at roughly twice this rate, i.e. ~10%/yr. The most rapidly expanding clones were those carrying SRSF2-P95H mutations, which grew at rates of over 50%/yr. Most hotspot mutations, including those at DNMT3A-R882, were not associated with faster growth than other mutations in the same gene. Growth of different clones bearing the same driver mutation varied by +/-5%/yr, proportionately impacting “slow” drivers most substantially.To investigate lifelong clonal behavior, we first used retrograde extrapolation of observed trajectories to infer the age at which each clone had begun to expand. This led to projected ages at clonal foundation that preceded conception for many clones, implying that their early growth must have been faster than the rate we observed during old age. This was most striking for DNMT3A, for which more than two thirds of projections were implausible (i.e. onset pre-conception), less common for TET2 and very uncommon for splicing factor genes. Quantification of the minimum lifetime rate at which clones must have grown in order to reach observed VAFs confirmed that deceleration was particularly marked for DNMT3A-mutant clones, whose early growth was at least twice as fast as growth during old age.To further characterize clonal dynamics over the human lifespan, we analysed hematopoietic phylogenies from 7 older individuals (aged 73-83 years), constructed using somatic mutations as lineage-tracing barcodes in 1,731 whole genome-sequenced hematopoietic colonies. We used the timing and density of clonal branching to age the onset of clonal expansions and to reconstruct their lifelong growth trajectories. In conjunction with findings from our longitudinal cohort, we revealed distinct patterns of clonal behavior. DNMT3A-mutant clones preferentially initiated and expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. In contrast, TET2 mutations were able to found clones fairly uniformly through life and drove more stable growth across ages. This disparity in behavior might explain why TET2 “overtook” DNMT3A as the most common CH driver after the age of 75 years. In diametric contrast to DNMT3A and unlike other genes, CH driven by mutant U2AF1 and SRSF2-P95H only initiated late in life and exhibited the fastest expansion dynamics.Finally, we explored the relationship between CH growth rates and malignant progression, building on our previous study of Acute Myeloid Leukemia (AML) risk prediction (Abelson et al, Nature 2018), and applying dN/dS analyses to published data (Papaemmanuil et al, Blood 2013 and NEJM 2016) to quantify selective pressures on different gene mutations in myeloid cancers. We found that mutations associated with faster CH growth were also those associated with higher risk of progression to AML (adjustedR 2=0.55, p=0.004) and were under the strongest selective pressure in AML and Myelodysplastic Syndromes (adjustedR 2=0.19, p=0.002).Collectively, our findings characterize the lifelong natural history of CH and give fundamental insights into the interactions between somatic mutation, aging and clonal selection. [Display omitted] DisclosuresCampbell: Mu Genomics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Vassiliou: Astrazeneca: Consultancy; STRM.BIO: Consultancy.

Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results from the Global, Prospective VerITI-8 Study

Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results from the Global, Prospective VerITI-8 Study

Integrated Genomic Analysis Identifies UBTF Tandem Duplications As a Subtype-Defining Lesion in Pediatric Acute Myeloid Leukemia

Children with acute myeloid leukemia (AML) have a dismal prognosis due to a high relapse rate; however, the molecular basis leading to relapsed pediatric AML has not yet been fully characterized. To define the spectrum of alterations common at relapse, we performed integrated profiling of 136 relapsed pediatric AML cases with RNA sequencing (RNA-seq), whole-genome sequencing, and target-capture sequencing. In addition to well-characterized fusion oncoproteins, such as those involving KMT2A (n=36, 26.5%) or NUP98 (n=18, 13.2%), we also identified somatic mutations in UBTF (upstream binding transcription factor) in 12 of 136 cases (8.8%) of this relapsed cohort.Somatic alterations of the UBTF gene, which encodes a nucleolar protein that is a component of the RNA Pol I pre-initiation complex to ribosomal DNA promoters, have rarely been observed in AML. In our cohort, all alterations can be described as heterozygous in-frame exon 13 tandem duplications (UBTF-TD), either at the 3' end of exon 13 of UBTF or of the entire exon 13 (Fig. A). As we noticed limited detection in our pipeline as a result of complex secondary indels alongside the duplications, we established a soft-clipped read-based screening method to detect UBTF-TD more efficiently. Applying the screening to RNA-seq data of 417 additional pediatric AMLs from previous studies and our clinical service, we identified 15 additional UBTF-TDs, many of which have not been previously reported. At the amino acid level, UBTF-TDs caused amino acid insertions of variable sizes (15-181 amino acids), duplicating a portion of high mobility group domain 4 (HMG4), which includes short leucine-rich sequences.UBTF-TD AMLs commonly occurred in early adolescence (median age: 12.6, range: 2.4-19.6), and 19 of the total 27 cases had either normal karyotype (n=12) or trisomy 8 (n=7). UBTF-TD is mutually exclusive from other recurrent fusion oncoproteins, such as NUP98 and KMT2A rearrangements (Fig. B), but frequently occurred with FLT3-ITD (44.4%) or WT1 mutations (40.7%). The median variant allele fraction (VAF) of the UBTF-TD was 48.0% (range: 9.7-66.7%). In four cases with data at multiple disease time points, the identical UBTF-TDs were present at high allele fractions at all time points, suggesting that UBTF-TD is a clonal alteration. tSNE analysis of the transcriptome dataset showed that UBTF-TD AMLs share a similar expression pattern with NPM1 mutant and NUP98-NSD1 AML subtypes, including NKX2-3 and HOXB cluster genes (Fig. C) . Altogether, these findings suggest that UBTF-TD is a unique subtype of pediatric AML.To address the impact of UBTF-TD expression in primary hematopoietic cells, we introduced UBTF-TD and UBTF wildtype expression vectors into cord blood CD34+ cells via lentiviral transduction. UBTF-TD expression promotes colony-forming activity and cell growth, yielding cells with a persistent blast-like morphology (Fig. D). Further, transcriptional profiling of these cells demonstrated expression of HOXB genes and NKX2-3, similar to UBTF-TD AMLs in patients, indicating that UBTF-TD is sufficient to induce the leukemic phenotype.To investigate the prevalence of UBTF-TDs in larger de novo AML cohorts, we applied the above UBTF-TD screening method to the available de novo AML cohorts of TCGA (n=151, adult), BeatAML (n=220, pediatric and adult), and AAML1031 (n=1035, pediatric). We identified UBTF-TDs in 4.3% (45/1035) of the pediatric AAML1031 cohort, while the alteration is less common (0.9%: 3/329, p=0.002) in the adult AML cohorts (Fig. E). In the AAML1031 cohort, UBTF-TDs remain mutually exclusive with known molecular subtypes of AML and commonly occur with FLT3-ITD (66.7%) and WT1 (40.0%) mutations and either normal karyotype or trisomy 8. The presence of UBTF-TDs in the AAML1031 cohort is associated with a poor outcome (Fig. F, median overall survival, 2.3 years) and MRD positivity; multivariate analysis revealed that UBTF-TD and WT1 are independent risk factors for overall survival within FLT3-ITD+ AMLs.In conclusion, we demonstrate UBTF-TD defines a unique subtype of AMLs that previously lacked a clear oncogenic driver. While independent of subtype-defining oncogenic fusions, UBTF-TD AMLs are associated with FLT3-ITD and WT1 mutations, adolescent age, and poor outcomes. These alterations have been under-recognized by standard bioinformatic approaches yet will be critical for future risk-stratification of pediatric AML. [Display omitted] DisclosuresIacobucci: Amgen: Honoraria; Mission Bio: Honoraria. Miller: Johnson & Johnson's Janssen: Current Employment. Mullighan: Pfizer: Research Funding; Illumina: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Amgen: Current equity holder in publicly-traded company.

Real-World Management of Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax-Based Regimens: Results from the AML Real World Evidence (ARC) Initiative

Real-World Management of Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax-Based Regimens: Results from the AML Real World Evidence (ARC) Initiative

Comparative Effectiveness of Venetoclax Combinations Vs Other Therapies Among Patients with Newly Diagnosed Acute Myeloid Leukemia: Results from the AML Real World Evidence (ARC) Initiative

Comparative Effectiveness of Venetoclax Combinations Vs Other Therapies Among Patients with Newly Diagnosed Acute Myeloid Leukemia: Results from the AML Real World Evidence (ARC) Initiative

Prediction of Early Death and Severe Infections during Novel Agent-Based Induction Therapy in Newly-Diagnosed Multiple Myeloma: An Intergroup Analysis from the German Speaking Myeloma Multicenter Group, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology Foundation and the European Myeloma Network

Prediction of Early Death and Severe Infections during Novel Agent-Based Induction Therapy in Newly-Diagnosed Multiple Myeloma: An Intergroup Analysis from the German Speaking Myeloma Multicenter Group, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology Foundation and the European Myeloma Network

Treatment of Relapsed/Refractory Waldenström Macroglobulinemia Patients: Final Clinical and Molecular Results of the Phase II Brb (Bendamustine, Rituximab and Bortezomib) Trial of the Fondazione Italiana Linfomi (FIL)

Treatment of Relapsed/Refractory Waldenström Macroglobulinemia Patients: Final Clinical and Molecular Results of the Phase II Brb (Bendamustine, Rituximab and Bortezomib) Trial of the Fondazione Italiana Linfomi (FIL)

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies

Daratumumab Plus Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): A Subgroup Analysis of Griffin

Daratumumab Plus Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): A Subgroup Analysis of Griffin

LocoMMotion: A Prospective, Non-Interventional, Multinational Study of Real-Life Current Standards of Care in Patients With Relapsed/Refractory Multiple Myeloma Who Received ≥3 Prior Lines of Therapy

LocoMMotion: A Prospective, Non-Interventional, Multinational Study of Real-Life Current Standards of Care in Patients With Relapsed/Refractory Multiple Myeloma Who Received ≥3 Prior Lines of Therapy

Genomic Landscape and Molecular Risk in Patients with Advanced Myelofibrosis Treated within the Multicenter Phase Ib/II MPNSG0212 (POMINC) Trial

Genomic Landscape and Molecular Risk in Patients with Advanced Myelofibrosis Treated within the Multicenter Phase Ib/II MPNSG0212 (POMINC) Trial

Integrated Safety Analysis of Tagraxofusp, a CD123-Directed Targeted Therapy, in Patients with Hematologic Malignancies

Integrated Safety Analysis of Tagraxofusp, a CD123-Directed Targeted Therapy, in Patients with Hematologic Malignancies

Second Versus First Wave of COVID-19 in Patients with MPN

Second Versus First Wave of COVID-19 in Patients with MPN

CC-92480, a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD) Agent, in Combination with Dexamethasone (DEX) and Bortezomib (BORT) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Phase 1/2 Study CC-92480-MM-002

CC-92480, a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD) Agent, in Combination with Dexamethasone (DEX) and Bortezomib (BORT) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Phase 1/2 Study CC-92480-MM-002