Top Abstracts to Watch from ASH 2021

The American Society of Hematology’s (ASH) annual meeting is a great opportunity to discover and discuss the latest developments in the treatment of blood disorders and malignancies. The staff of Cleveland Clinic Cancer Center’s Department of Hematology and Medical Oncology has chosen these abstracts presented at ASH 2021 as the most compelling, clinically relevant and potentially practice-changing that included research from our clinical team.

LBA-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

This study was the first large clinical trial to demonstrate the superiority of any treatment regimen to R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

LBA-3 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)

All key primary and secondary endpoints were met in this Phase 3 study. Specifically, once-monthly 80 mg SC fitusiran prophylaxis demonstrated a significant reduction in ABR, AsBR and AJBR (all ~90%) in people with severe hemophilia A or B without inhibitors compared with OD treatment. This reduction in bleeding was associated with a meaningful improvement in HRQoL. Reported TESAEs were generally consistent with the previously identified risks of fitusiran. With the aim of further enhancing the benefit-risk profile of fitusiran, a revised regimen with reduced dose and frequency is being evaluated in ongoing clinical studies.

2 Primary Analysis of ZUMA‑7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard‑of‑Care Therapy in Patients with Relapsed/Refractory Large B-Cell LymphomaClinically Relevant Abstract

91 Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Versus Standard of Care (SOC) with Salvage Chemotherapy (CT) Followed By Autologous Stem Cell Transplantation (ASCT) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Randomized Phase 3 Transform Study

These two papers described head-to-head trials of CAR T-cell therapy vs. second-line chemotherapy and autologous stem cell transplantation in patients with relapsed DLBCL. Both trials met their primary endpoints and will likely lead to a significant increase in the use of anti-CD19 CAR T-cell therapy rather than chemotherapy for patients with high-risk relapsed DLBCL.

14 Updated Phase I/II Safety and Efficacy Results for Oral Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed/Refractory Immune Thrombocytopenia

Oral rilzabrutinib 400 mg twice daily was shown to be well-tolerated and had durable, clinically significant platelet responses across subgroups and with extended treatment in patients with heavily pretreated immune thrombocytopenic purpura.

159 Subcutaneous Daratumumab with Bortezomib, Cyclophosphamide, and Dexamethasone in Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: 18-Month Analysis of the Phase 3 ANDROMEDA Study

468 Safety and Tolerability of Cael-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase 2 Trial

These two papers highlighted advances in the treatment of AL amyloidosis. One showed improvements in hematologic and organ responses when daratumumab was added to the backbone of bortezomib, cyclophosphamide and dexamethasone for patients with newly diagnosed AL amyloidosis. The second abstract described the potential for amyloid removal from organs by CAEL-101.

160 Early, Deep, and Durable Responses, and Low Rates of Cytokine Release Syndrome with REGN5458, a BCMAxCD3 Bispecific Monoclonal Antibody, in a Phase 1/2 First-in-Human Study in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

One example of high response rates seen using bispecific antibodies in treatment of relapsed myeloma.

651 Universal Updated Phase 1 Data Validates the Feasibility of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma

Allogenic T-cell therapy for myeloma addresses many logistical challenges for CAR T-cell therapy. The UNIVERSAL myeloma trial using ALLO-715 CAR T cells has shown clinical efficacy with a response rate above 60%, high VGPR+ rate of 38.5%, and high MRD negativity in the latest cohort without requiring leukapheresis or bridging therapy.

1019 Caplacizumab Is Effective in Treating Immune-Mediated Thrombotic Thrombocytopenic Purpura in Real-World Scenarios and May Lower Mortality: An Aggregative Analysis

In view of all treatment-related outcomes, the data presented in this abstract argues strongly in favor of the early, consistent use of caplacizumab in all patients with acquired thrombotic thrombocytopenic purpura.