Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin on Patients with Relapsed/Refractory Classical Hodgkin Lymphoma: Exploratory Analysis of the Randomized, Phase 3 Keynote-204 Study By Prior Lines of Therapy

The open-label, international, randomized, phase 3 KEYNOTE-204 (NCT02684292) study showed that in pts with R/R cHL, the PD-1 inhibitor pembro was superior to BV and demonstrated statistically significant, clinically meaningful improvement in PFS, with safety consistent with previous reports. This post hoc exploratory analysis of KEYNOTE-204 evaluated pembro vs BV by number of prior lines of therapy. https://ashpublications.org/blood/article/136/Supplement%201/12/470837/Effect-of-Pembrolizumab-Pembro-Monotherapy-Versus

Optimal Duration of Imatinib Treatment / Deep Molecular Response for Treatment-Free Remission after Imatinib Discontinuation from a Canadian Tyrosine Kinase Inhibitor Discontinuation Trial

Several clinical factors have been proposed to predict successful tyrosine kinase inhibitor (TKI) discontinuation for treatment-free remission (TFR), among which a longer duration of total TKI or deep molecular response (DMR) duration correlate with increased success of TFR. Although many guidelines have been proposed to safely select patients who would be candidates for TFR attempt, there is some discrepancy regarding which duration of DMR and/or Imatinib (IM) treatment optimally stratifies patients according to their probability of TFR success. These suggested DMR or IM treatment durations are often the result of a panel consensus, and the method of calculation of these thresholds as categorical values is not provided. Thus, there is a practical need for an evidence-based determination of duration of IM therapy while awaiting TFR attempt to establish if the likelihood of successful TKI discontinuation reaches an optimal maximum after a certain duration of treatment and/or DMR. The present study attempted to define the optimal (i.e. shortest) duration of IM treatment or DMR that predicts TFR success at a specified level of confidence. https://ashpublications.org/blood/article/136/Supplement%201/54/471081/Optimal-Duration-of-Imatinib-Treatment-Deep

Novelties on the treatment of Multiple Myeloma and Plasma Cell Disorders

The key finding that we have learned about multiple myeloma on ASH 2020. About frontline therapy, early relapse therapy and late relapse therapy.  - GRIFFIN trial  - FORTE trial  - APOLLO trial  - CAR T-Cell Therapies  - Bispecific drugs

Comprehensive summary of novel multiple myeloma data from ASH2020

Summarized studies: Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in the Randomized Forte Trial https://ash.confex.com/ash/2020/webprogram/Paper136907.html Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial https://pubmed.ncbi.nlm.nih.gov/32325490/ Updated Analysis of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma: The Phase 3 Maia Study https://ash.confex.com/ash/2020/webprogram/Paper134847.html Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial https://pubmed.ncbi.nlm.nih.gov/31836199/ Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Analysis of the IFM 2009 Trial https://ash.confex.com/ash/2020/webprogram/Paper134538.html The Phase 3 TOURMALINE-MM2 Trial: Oral Ixazomib, Lenalidomide, and Dexamethasone Vs Placebo-Rd for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma https://ash.confex.com/ash/2020/webprogram/Paper137007.html Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone Versus Pomalidomide and Dexamethasone Alone in Patients  with Relapsed/Refractory Multiple Myeloma (RRMM) https://ash.confex.com/ash/2020/webprogram/Paper135874.html Daratumumab (DARA) Plus Carfilzomib, Pomalidomide, Dexamethasone (KPd) in Lenalidomide Refractory Multiple Myeloma (MM): A Multi-Center MMRC Study https://ash.confex.com/ash/2020/webprogram/Paper141029.html BCMA Targeted Therapies updates CAR T-cell Therapies updates Part 1 Results of a Dose Finding Study of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide (POM) and Dexamethasone (DEX) for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM) https://ash.confex.com/ash/2020/webprogram/Paper134836.html

Comparison of Gilteritinib and Salvage Chemotherapy in FLT3-Mutated Acute Myeloid Leukemia on the Number Needed to Treat for Various Clinical Outcomes: A Secondary Analysis of the Admiral Trial

FMS-like receptor tyrosine kinase-3 (FLT3) mutations are common in acute myeloid leukemia (AML) and are associated with poor prognosis. Historically, patients with relapsed/refractory (R/R) FLT3 mutation–positive (FLT3mut+) AML experienced dismal survival outcomes. Gilteritinib, a highly potent and selective FLT3 inhibitor, was recently approved as the first targeted therapy for patients with R/R FLT3mut+ AML, and has the potential to bring significant clinical benefits to these patients. The randomized, phase 3 ADMIRAL trial (NCT02421939; Perl, et al. 2019) was the first head-to-head study that evaluated 120-mg/day gilteritinib versus salvage chemotherapy in R/R FLT3mut+ AML patients. The ADMIRAL trial demonstrated that gilteritinib was superior to salvage chemotherapy based on significantly longer median overall survival (OS) and higher response rates, including complete remission/complete remission with partial hematological recovery (CR/CRh), composite CR (CRc), and hematopoietic stem cell transplantation (HSCT) rate. Based on these results, the current study estimated the number needed to treat (NNT) with gilteritinib, compared with salvage chemotherapy, in order to evaluate its clinical benefit with CR/CRh, CRc, 1-year OS, and HSCT rates. https://ash.confex.com/ash/2020/webprogram/Paper136184.html

Polatuzumab Vedotin Plus Venetoclax with Rituximab in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Primary Efficacy Analysis of a Phase Ib/II Study

Polatuzumab vedotin (Pola) combined with rituximab (R) demonstrated activity and tolerability in a Phase (Ph) II trial of patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (Morschhauser et al. Lancet 2019). The pro-survival MCL-1 protein has been identified as a mechanism of resistance to venetoclax (Ven), a potent inhibitor of BCL-2, in non-Hodgkin lymphoma cell lines. Preclinical studies have demonstrated that concurrent treatment with Pola promotes MCL-1 degradation and enhances anti-tumor efficacy in vivo, thus providing a strong rationale for the combination with Ven (Amin et al. AACR 2020). We sought to determine whether the combination of Pola-Ven-R might further enhance anti-tumor response. Here, we present the primary efficacy and safety analysis from a Ph Ib/II study of Pola-Ven-R in pts with R/R DLBCL (GO29833; NCT02611323). https://ashpublications.org/blood/article/136/Supplement%201/45/470363/Polatuzumab-Vedotin-Plus-Venetoclax-with-Rituximab

Highlights of the Late-Breaking Abstracts Session of ASH 2020

Summarized studies: Driver Mutation Acquisition in Utero and Childhood Followed By Lifelong Clonal Evolution Underlie Myeloproliferative Neoplasms https://ashpublications.org/blood/article/136/Supplement_2/LBA-1/474188/Driver-Mutation-Acquisition-in-Utero-and-Childhood A Multicentre Randomised Trial of First Line Treatment Pathways for Newly Diagnosed Immune Thrombocytopenia: Standard Steroid Treatment Versus Combined Steroid and Mycophenolate. the Flight Trial https://ashpublications.org/blood/article/136/Supplement_2/LBA-2/474192/A-Multicentre-Randomised-Trial-of-First-Line Enhancer Hijacking of BCL11B Defines a Subtype of Lineage Ambiguous Acute Leukemia https://ash.confex.com/ash/2020/webprogram/Paper143881.html Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase Previously Treated with ≥2 Tyrosine Kinase Inhibitors https://ash.confex.com/ash/2020/webprogram/Paper143816.html ETNK1 Mutations in Atypical Chronic Myeloid Leukemia Induce a Mutator Phenotype That Can be Reverted with Phosphoethanolamine https://ash.confex.com/ash/2020/webprogram/Paper143852.html First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies https://ash.confex.com/ash/2020/webprogram/Paper143560.html

Ruxolitinib Vs Best Available Therapy in Patients with Steroid-Refractory/Steroid-Dependent Chronic Graft-Vs-Host Disease: Primary Findings from the Phase 3, Randomized REACH3 Study

Standard first-line treatment of cGVHD includes systemic corticosteroids; however, about 50% of patients (pts) are steroid refractory or dependent (SR/D) and require additional treatment. The best second-line therapy option has not yet been defined. RUX, an oral JAK1/2 inhibitor, was superior to BAT in SR acute GVHD (aGVHD) in a phase 3 study (REACH2). Here we present the primary analysis of the REACH3 study (NCT03112603), a phase 3, open-label, randomized study evaluating RUX vs BAT in pts with SR/D cGVHD. https://ash.confex.com/ash/2020/webprogram/Paper137694.html

What are the trends in lymphoma therapy?

On ASH 2020 there were a lot of exciting study but not much that are practice changing. There are a lot of immune mediated strategies on the horizon.

Effects of Tranexamic Acid Prophylaxis on Bleeding Outcomes in Hematologic Malignancy: The a-TREAT Trial

Despite optimal prophylactic platelet (plt) transfusion therapy for severe thrombocytopenia in patients undergoing treatment for hematologic malignancy, WHO Grade 2 or greater bleeding continues to occur at rates of 43% to 70%. Although antifibrinolytic therapy has been shown to reduce bleeding and transfusion needs in patients with inherited bleeding disorders and in multiple surgical settings, evidence in therapy-induced thrombocytopenia in hematologic malignancy is lacking. The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT) evaluated the effects of prophylactic TXA as an adjunct to routine transfusion therapy on bleeding and transfusion requirements in a multicenter, double blind placebo controlled randomized clinical trial in patients undergoing treatment for hematologic malignancy. https://ashpublications.org/blood/article/136/Supplement%201/1/470165/Effects-of-Tranexamic-Acid-Prophylaxis-on-Bleeding

A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplan

Recent advances in the treatment of myelodysplastic syndrome (MDS) have improved patient survival and quality of life (QOL), while reducing transfusion burden. However, allogeneic hematopoietic cell transplantation (HCT), widely used in younger MDS patients, remains the only curative therapy for MDS. While transplantation outcomes among selected older patients with MDS are similar to younger patients with MDS, early transplantation for older patients is infrequently offered since the relative benefits of HCT over non-HCT therapy in have not been well defined in this patient group. We conducted a multi-center, biologic assignment trial in older individuals with high risk MDS to define the benefit of HCT over non-HCT therapy. https://ash.confex.com/ash/2020/webprogram/Paper136828.html

Discovery of biomarkers for targeted therapy in B cell lymphoma

ABC-DLBCLs are among the most aggressive DLBCLs. Genome sequencing studies identified BCL10 gain-of-function mutations in DLBCL mostly within the ABC-DLBCLs. ABC-DLBCLs were recently split into further subtypes according to their genomic characteristics, among which BCL10 somatic mutations were most common in BN2/Cluster 1 cases. These are likely transformed marginal zone lymphomas and were recently suggested to be sensitive to ibrutinib treatment. https://ashpublications.org/blood/article/136/Supplement%201/2/469831/BCL10-Gain-of-Function-Mutations-Aberrantly-Induce

Newly Diagnosed Childhood AML Patients Treated with Bortezomib Show Superior Survival If CD74 Is Expressed: A Report of 991 Patients from the Children’s Oncology Group AAML1031 Protocol

CD74 is a type II transmembrane protein expressed on antigen-presenting cells and an MHC class II chaperone. It has been associated with tumor progression and metastasis in solid tumors, and its expression has been suggested to serve as a prognostic factor in many cancers, with higher relative expression associated with oncogenesis. As the expression of CD74 has been associated with response to bortezomib in multiple myeloma, we inquired whether such correlation might be seen in pediatric AML. We prospectively evaluated CD74 expression by difference from normal (ΔN) flow cytometry and correlated expression with clinical characteristics and outcome as part of Children’s Oncology Group protocol AAML1031 that randomized patients younger than 30 years of age with de novo AML to standard treatment with (Arm B) or without (Arm A) bortezomib. The addition of bortezomib to standard chemotherapy increased toxicity but did not improve survival. Given the association of CD74 with B-lymphoid neoplasms and bortezomib’s known efficacy in B-cell neoplasms and multiple myeloma, we hypothesized that within Arm B, the patients with CD74 expression would have a more favorable outcome.  https://ash.confex.com/ash/2020/webprogram/Paper142659.html

Acute Myeloid Leukemia: Using Available Evidence and Guidelines to Make Sense of a Rapidly Evolving Treatment Paradigm

Review of the latest clinical data, NCCN Guidelines updates, and management of different patient case studies. https://ash.confex.com/ash/2020/webprogram/Session19454.html

The Immune System in Multiple Myeloma

Updates from the 62nd annual ASH meeting in Multiple Myeloma. Summarized trials: - IFM 2009 Trial - FORTE trial - CANDOR trial - APOLLO trial - CAR T-cell therapies, bispecifics

Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase Previously Treated with ≥2 Tyrosine Kinase Inhibitor

Asciminib, unlike all approved TKIs that bind to the ATP site of the BCR-ABL1 oncoprotein, is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with a new mechanism of action. BOS, an ATP-competitive TKI, has shown clinical efficacy in pts who received ≥2 TKIs and in newly diagnosed CML, in prospective clinical trials. We asked if asciminib could provide superior efficacy to BOS beyond 2nd line, based on the clinical activity of asciminib monotherapy in heavily pretreated pts with CML in a phase 1 study. https://ash.confex.com/ash/2020/webprogram/Paper143816.html

Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM): Primary Analysis Results from the Randomized, Open-Label, Phase 3 Study Candor

Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study

The QUAZAR AML-001 Maintenance Trial: Results of a Phase III International, Randomized, Double-Blind, Placebo-Controlled Study of CC-486 (Oral Formulation of Azacitidine) in Patients with Acute Myeloid Leukemia (AML) in First Remission

Validation of BCL11A As Therapeutic Target in Sickle Cell Disease: Results from the Adult Cohort of a Pilot/Feasibility Gene Therapy Trial Inducing Sustained Expression of Fetal Hemoglobin Using Post-Transcriptional Gene Silencing

A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in High and Intermediate Risk First Relapse of B-ALL in Children and Adolescents/Young Adults Demonstrates Superior Efficacy and Tolerability of Blinatumomab

Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study: A Perioperative Management Plan for Patients with Atrial Fibrillation Who Are Receiving a Direct Oral Anticoagulant

Safety and Efficacy of Emapalumab in Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis

A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912)

Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA)

Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia

Best of ASH

Long Term Follow-up after SCRI-CAR19v1 Reveals Late Recurrences As Well As a Survival Advantage to Consolidation with HCT after CAR T Cell Induced Remission

A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes

Initial Report of the Beat AML Umbrella Study for Previously Untreated AML: Evidence of Feasibility and Early Success in Molecularly Driven Phase 1 and 2 Studies

Multicenter Microbiota Analysis Indicates That Pre-HCT Microbiota Injury Is Prevalent across Geography and Predicts Poor Overall Survival

Rivaroxaban Thromboprophylaxis in High-Risk Ambulatory Cancer Patients Receiving Systemic Therapy: Results of a Randomized Clinical Trial (CASSINI)