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Key Studies From ASH 2023
An Expert’s Guide to ASH 2023: Preview of the Top Abstracts

Released: December 07, 2023

Catherine M. Broome
Catherine M. Broome, MD
Ian Flinn
Ian Flinn, MD, PhD
Sagar Lonial
Sagar Lonial, MD, FACP
Brady L. Stein
Brady L. Stein, MD, MHS
Eunice S. Wang
Eunice S. Wang, MD
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The 2023 American Society of Hematology (ASH) Annual Meeting and Exposition will feature significant results from numerous clinical studies in varied hematologic diseases. As part of CCO’s Independent Conference Coverage of ASH 2023, experts have identified their most anticipated abstracts, as listed below. Remember to check the CCO website often as the meeting unfolds for downloadable slidesets summarizing the data from these studies and more. After the meeting, join us for our live, interactive “Conference to Clinic” webinar on Saturday, January 13 as experts discuss some of the most important data presented during ASH 2023 and how they plan to change their practice, as well as answer your questions. Finally, read our CME-certified online modules providing expert analyses and insights into the clinical implications of the new findings.

Top Picks: Myeloproliferative Neoplasms
For myeloproliferative neoplasms, Brady L. Stein, MD, MHS, identified the following as top abstracts to watch.

  • TRANSFORM-1: data from a randomized phase III study of the BCL-2 family inhibitor navitoclax plus ruxolitinib vs placebo plus ruxolitinib for patients with intermediate-2‒ or high-risk myelofibrosis (MF) with splenomegaly and MF-related symptoms who had received no prior JAK2 inhibitor treatment (abstract 620). 
  • MANIFEST-2: data from a randomized phase III study of pelabresib (a BET inhibitor) plus ruxolitinib vs placebo plus ruxolitinib for patients with intermediate-1 or higher‒risk MF with splenomegaly and MF-related symptoms who had received no prior JAK inhibitor treatment (abstract 628). 
  • A phase II study of bomedemstat (an oral LSD1 inhibitor) plus ruxolitinib for patients with MF who had no previous treatment or a suboptimal response to ruxolitinib (abstract 621). 
  • A phase IIb study of bomedemstat for patients with essential thrombocythemia resistant to or intolerant of ≥1 standard treatment (abstract 747).
  • RuxoBEAT: interim data from a randomized phase IIb study of ruxolitinib vs best available therapy for patients with high-risk polycythemia vera who have received no or limited prior cytoreductive therapy (abstract 619). 

Top Picks: Multiple Myeloma
For multiple myeloma (MM), Sagar Lonial, MD, identified the following as key abstracts to watch.

  • PERSEUS: primary progression-free survival rates from a phase III study of SC daratumumab plus bortezomib/lenalidomide/dexamethasone (VRd) induction and consolidation and daratumumab-R maintenance vs VRd induction and consolidation followed by R maintenance in transplant-eligible patients with newly diagnosed MM (abstract LBA-1). 
  • IsKia: postconsolidation measurable residual disease (MRD) negativity rates from a phase III study of isatuximab/carfilzomib/lenalidomide/dexamethasone vs carfilzomib/lenalidomide/dexamethasone in transplant-eligible patients with newly diagnosed MM (abstract 4). 
  • A real-world evaluation of daratumumab plus VRd compared with historical VRd in transplant-eligible patients with newly diagnosed MM (abstract 647). 

Additional studies to watch in MM:

  • LINKER-MM1: updated response results from a phase I/II study of the BCMA-targeted bispecific antibody linvoseltamab for patients with R/R MM who either progressed on ≥3 lines of therapy or who were at least triple-class refractory (abstract 4746).
  • Updated MRD negativity rates from a phase I/II study of venetoclax, daratumumab, and dexamethasone vs daratumumab plus bortezomib/dexamethasone in patients with R/R t(11;14)-positive MM who had received ≥1 prior line of therapy (abstract 338).
  • CENTARUS: final results from a phase II study of daratumumab monotherapy for patients with intermediate- or high-risk smoldering MM (abstract 210).

Top Picks: Nonmalignant Hematologic Disorders
Catherine M. Broome, MD, identified the following as important abstracts to watch for sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNH), and cold agglutinin disease (CAD).

SCD:

  • BMT CTN 1507: prospective, multicenter phase II study of reduced-intensity HLA-haploidentical bone marrow transplant with posttransplant cyclophosphamide in adult patients with severe SCD (abstract LBA-4); data to be presented at the meeting suggest positive results with durable donor engraftment at 2 years and a low mortality rate suitable for a potential curative therapy with a manageable safety profile in patients with severe organ toxicity, stroke, and pulmonary hypertension that would otherwise be excluded from myeloablative gene therapy trials.
  • Pooled efficacy, safety, and health-related quality-of-life data after 5 years of follow-up from the phase I/II HGB-206 and phase III HGB-210 studies of lovo-cel, a gene therapy using a lentiviral vector encoding for a modified β-globin gene, in patients with SCD and recurrent severe vaso-occlusive events (VOEs) or history of evident stroke (abstract 1051); data to be presented at the meeting suggest that one-time treatment with lovo-cel yields sustained hemoglobin A production with near-complete resolution of total VOEs and severe VOEs up to 18 months following treatment, a safety profile consistent with myeloablative conditioning, and improvement in pain-related and fatigue outcomes.
  • REACH: initial feasibility and safety results from a prospective, open-label phase I/II study of hydroxyurea dose escalation to a maximum tolerated dose in 635 children with sickle cell anemia from sub-Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda) (abstract 6); data to be presented suggest that this large study will confirm the benefits of hydroxyurea in children with SCD and provides evidence that dosing to a maximum tolerated dose is safe and requires less frequent monitoring than originally thought, allowing for broader prescribing practices in all children with SCD. 

 PNH:

  • APPLY-PNH: final 48-week results from the multicenter phase III trial of iptacopan, an oral inhibitor of factor B, in patients with PNH previously treated with anti-C5 therapy for ≥6 months and persistent anemia; these results provide healthcare professionals with longer-term data regarding single-agent iptacopan therapy in patients with PNH, with additional data regarding common clinical concerns including breakthrough hemolysis (BTH) and major vascular events (abstract 571). Combined trial data to be presented on the incidence, severity, and management strategies for BTH will clarify the main clinical concerns regarding this oral therapy; based on results from APPLY-PNH and APPOINT-PNH studies, iptacopan recently received FDA approval as the first oral monotherapy treatment of adults with PNH (abstract 1338).
  • ALPHA: long-term results from a phase III study evaluating danicopan, a first-in-class inhibitor of factor D, as add-on therapy to ravulizumab or eculizumab vs placebo in patients with PNH and clinically significant extravascular hemolysis (abstract 576); results to be presented at ASH 2023 provide awaited long-term data for efficacy, safety, and BTH for patients treated with combination therapy with danicopan and anti-C5 therapy and confirm that the combination of anti-C5 therapy with oral factor D inhibition is safe and effective. 

 CAD:

  • CADENZA and CARDINAL: post hoc analysis with pooled safety data from 2 phase III studies of sutimlimab (a first-in-class humanized monoclonal antibody against complement C1) in patients with CAD (abstract 3833); this combined safety dataset will provide healthcare professionals with information documenting the safety of long-term use of classical pathway complement C1 inhibition in patients with CAD.

Top Picks: Leukemias and Myelodysplastic Syndromes
For leukemias and myelodysplastic syndromes (MDS), Eunice S. Wang, MD, identified the following as key abstracts to watch.

  • Quantum-First: analysis showing that, in patients with newly diagnosed FLT3-ITD+ acute myeloid leukemia (AML) who achieved a complete response with quizartinib plus intensive chemotherapy (7+3), FLT3-ITD–specific MRD clearance during induction/consolidation was linked with better overall survival (abstract 832). Quizartinib added to 7+3 for newly diagnosed FLT3-ITD–mutant AML has become the standard of care for fit patients since the drug’s approval by the FDA in June 2023. This update from Perl and colleagues highlights the achievement of deeper and more sustained FLT3-ITD MRD-negative responses during upfront therapy as a significant predictor of overall survival and outcomes of therapy.
  • COMMANDS: full analysis of a phase III trial evaluating the efficacy of luspatercept vs epoetin alfa in patients with transfusion-dependent lower-risk MDS (LR-MDS) who are erythropoiesis-stimulating agent naive (abstract 193). Luspatercept is a TGF-β ligand inhibitor that reduces ineffective erythropoiesis in LR-MDS. This analysis confirms that luspatercept is superior to epoetin alfa for LR-MDS. These results, particularly in patients with LR-MDS characterized by ringed sideroblasts, support luspatercept as a new frontline standard of care for LR-MDS in place of erythropoiesis-stimulating agents
  • AUGMENT-101: data from a pivotal phase II trial of revumenib in patients with R/R KMT2-rearranged acute leukemia (formerly known as mixed lineage leukemia, or MLL) (abstract LBA-5). Results with revumenib, a novel menin inhibitor for therapy of patients with KMT2A-rearranged acute leukemia, confirm the clinical activity (response rate) and toxicities (differentiation syndrome, QTC prolongation) of this targeted agent for this biological subset of disease. Revumenib will be submitted for FDA approval for this disease. 

Additional studies to watch in leukemias and MDS:

  • Updated results from an ongoing multicenter trial evaluating an oral arsenic trioxide/all-trans retinoic acid/ascorbic acid regimen for newly diagnosed acute promyelocytic leukemia (abstract 157).
  • A study from the French Innovative Leukemia Organization shows that patients with AML who discontinued venetoclax and/or azacitidine for reasons other than progressive disease have a prolonged treatment-free remission and overall survival (abstract  161).
  • Phase I/II study of the combination of quizartinib, venetoclax, and decitabine in FLT3-ITD–mutated AML (abstract 158).
  • ALLG CML13 Ascend-CML: patients with chronic myeloid leukemia in chronic phase who were treated with asciminib experienced early and major molecular responses (abstract 865).
  • Stimulus-AML2: preliminary results from a phase Ib/II trial evaluating the efficacy of sabatolimab, a TIM-3 inhibitor, for patients with MRD-positive AML after an allogeneic stem cell transplantation (abstract 59).
  • IMerge: results of a phase III trial evaluating the use of imetelstat for achieving red blood cell transfusion independence in patients with LR-MDS across different risk categories (abstract 194). 

Top Picks: Lymphomas and Chronic Lymphocytic Leukemia
For lymphomas and chronic lymphocytic leukemia (CLL), Ian Flinn, MD, PhD, identified the following as top abstracts to watch.

  • SYMPATICO: primary analysis of a phase III trial evaluating combination therapy with ibrutinib plus venetoclax vs ibrutinib plus placebo in R/R mantle cell lymphoma (MCL) (abstract LBA-2). BTK inhibitor monotherapy has become the most common treatment approach in R/R MCL. This study demonstrates a significant progression-free survival benefit with the addition of venetoclax to a BTK inhibitor and is potentially practice changing in this setting.
  • TRANSCEND FL: primary analysis of a phase II study evaluating second-line therapy with lisocabtagene maraleucel for patients with high-risk R/R follicular lymphoma (FL) (abstract 602). The optimal second-line treatment for patients with FL who experience disease progression within 2 years (ie, POD24) is unclear. This study shows promising efficacy of lisocabtagene maraleucel in this setting, with less toxicity than typically seen with CAR T-cell therapy in more aggressive lymphomas.
  • Initial results of a phase II study evaluating first-line SC mosunetuzumab for patients with high tumor burden FL (abstract 604). Although the bispecific antibody mosunetuzumab is an important addition to third-line treatment options for FL, many patients would prefer a chemotherapy-free approach as initial treatment. This study demonstrates a high overall response rate and complete response rate and a favorable safety profile with mosunetuzumab as initial therapy for FL.
  • SWOG S1826: subset analysis in patients aged 60 years and older from a randomized phase III trial evaluating nivolumab plus doxorubicin/vinblastine/dacarbazine (AVD) vs brentuximab vedotin plus AVD in advanced-stage Hodgkin Lymphoma (HL) (abstract 181). The treatment of HL in patients older than 60 years of age can be challenging because of decreased tolerance to therapy. This subgroup analysis demonstrates remarkable differences in tolerance and subsequently efficacy with nivolumab plus AVD vs brentuximab vedotin plus AVD in these patients. 

Additional studies to watch in lymphomas and CLL:

  • ELARA: 3-year follow-up results from a phase II trial evaluating tisagenlecleucel in patients with R/R FL (abstract 601).
  • BOVen: results from a phase II trial evaluating zanubrutinib, obinutuzumab, and venetoclax in patients with treatment-naive, TP53-mutated MCL (abstract 738).
  • EPCORE NHL-5: results from arm 1 of a phase Ib/II trial evaluating SC epcoritamab plus lenalidomide in R/R diffuse large B-cell lymphoma (abstract 438).
  • ELM-2: final analysis of a phase II study evaluating odronextamab in patients with R/R diffuse large B-cell lymphoma (abstract 436).
  • VALENTINE-PTCL01: primary results from the phase II trial evaluating valemetostat monotherapy in patients with R/R peripheral T-cell lymphomas (abstract 302).
  • SGN35-027 part C: results from a phase II trial evaluating the addition of nivolumab to brentuximab vedotin, doxorubicin, and dacarbazine for early-stage classical HL (abstract 611).
  • TRANSCEND CLL 004: 24-month median follow-up of a phase I/II study evaluating lisocabtagene maraleucel in R/R CLL/small lymphocytic lymphoma (abstract 330).
  • ELEVATE-TN: 6-year follow-up results from a phase III trial evaluating acalabrutinib with or without obinutuzumab vs obinutuzumab plus chlorambucil in previously untreated CLL (abstract 636).

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