ASH 2018 Top 10 Abstracts

Hard hitters that caught our attention

The American Society of Hematology’s annual meeting provides an excellent opportunity to discover recent developments in the field. The staff of Cleveland Clinic Cancer Center’s Department of Hematology and Medical Oncology finds these abstracts the most compelling, clinically relevant and potentially transformative to the practice:

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1.) Late-Breaking Abstract No. 1
Rivaroxaban Thromboprophylaxis in High-Risk Ambulatory Cancer Patients Receiving Systemic Therapy: Results of a Randomized Clinical Trial (CASSINI)
This was a randomized, placebo-controlled study assessing the use of rivaroxaban as thromboprophylaxis in patients with various cancers and intermediate to high Khorana scores (≥ 2) that were initiating systemic chemotherapy regimens. Rivaroxaban significantly reduced venous thromboembolism (VTE) and VTE-related death during the on-treatment period but not during the full study period. Over one-third of events occurred after discontinuation of the study drug. The incidence of major bleeding was low. The Khorana risk score cutoff of ≥ 2 identified cancer patients at high risk of thrombotic events both at baseline (4.53 percent) and during study (8.79 percent with additional 1.66 percent arterial events in placebo group)

2.) Late-Breaking Abstract No. 2
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)
This abstract is practice changing due to the 45 percent reduction in risk of disease progression or death with the upfront use of daratumumab in combination with lenalidomide and dexamethasone compared with lenalidomide and dexamethasone. The progression-free survival of about 70 percent at 42 months for the daratumumab, lenalidomide and dexamethasone-containing arm is impressive considering the relatively little toxicity associated with the addition of daratumumab.

3.) Late-Breaking Abstract No. 4
A Randomized Phase 3 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)

And

Abstract No. 6
Ibrutinib Alone or in Combination with Rituximab Produces Superior Progression-Free Survival (PFS) Compared with Bendamustine Plus Rituximab in Untreated Older Patients with Chronic Lymphocytic Leukemia (CLL): Results of Alliance North American Intergroup Study A041202
These two studies highlight the efficacy of targeted treatment with the oral Btk inhibitor ibrutinib in frontline treatment of CLL and compare them with traditional chemotherapy. Of note, both studies show toxicities from both ibrutinib and chemotherapy, particularly in older patients. For patients over 65 years old, there was no overall survival benefit, so it may be appropriate in some patients to use more moderate, time-limited treatment such as bendamustine and rituximab. However, ibrutinib is more active for patients with high-risk genetic features, and optimal management of CLL patients will require a risk-adapted approach based on molecular features as well as patient comorbidities.

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4.) Abstract No. 1
The MEDALIST Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Patients With Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) Associated Anemia With Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Luspatercept is an erythroid maturation agent that has particular activity in MDS patients with ring sideroblasts. In this Phase 3 potentially pivotal trial, transfusion-dependent, lower-risk MDS patients with ring sideroblasts were randomized to receive luspatercept or placebo. Those treated with luspatercept had a 38 percent transfusion independence response rate, compared with 13 percent in the placebo group, which lasted a median of 31 weeks.

5.) Abstract No. 91
Axicabtagene Ciloleucel (Axi-cel) CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: Real World Experience
CAR-T cell therapy has been FDA approved for about one year for commercial use, and many patients receiving Axi-Cel for relapsed/refractory diffuse large B-cell lymphoma are generally more ill than patients treated on the registration clinical trial. This real world experience of about 300 patients from multiple U.S. academic medical centers shows that, despite more comorbidities and other medical conditions that would have precluded trial participation, patients in the real world can receive Axi-Cel with an acceptable safety profile. In addition, the efficacy assessment showed similar rates of an overall response rate of about 80 percent with about 50 percent complete remissions, which is similar to previously published data from the registration trial.

6.) Abstract No. 793
A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes

And

Abstract No. 206
A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Stem Cell Transplant in Patients with Myelodysplastic Syndromes: On Behalf of the CIBMTR Chronic Leukemia Committee
This study applied artificial intelligence programming to a training cohort of almost 1500 MDS patients and a validation cohort of over 800 MDS patients to determine prognosis using clinical and molecular characteristics. The new model was found to be far more accurate than the current standard prognostic systems (the IPSS and revised IPSS) irrespective of which treatments patients received. Number 206 applied the same methodology in a cohort of patients with MDS who had received allogeneic transplantation, and the methodology again provided personalized prognostic information.

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7.) Abstract No. 301
Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial
This study demonstrates that ixazomib is a suitable agent for post-transplant maintenance for patients with NDMM. The study showed a 28 percent reduction in the risk of progression and death as well as a 39 percent improvement in PFS with ixazomib maintenance. This agent can be considered for patients who cannot tolerate or are poor candidates for lenalidomide maintenance.

8.) Abstract No. 517 
Platelet Contraction Force as a Biophysical Biomarker for Bleeding Risk in Patients with Immune Thrombocytopenia
In this study, the investigators explored the clinical utility of a novel platelet function test that measures platelet contractility at a single platelet level. They found that patients whose platelets had low contractility were at significantly higher risk of thrombocytopenic bleeding. Using a predefined average force cutoff value, they found that low forces identified bleeding in ITP with 100 percent sensitivity and 89.4 percent specificity. This test may be clinically useful in identifying those thrombocytopenic patients at highest bleeding risk.

9.) Abstract No. 601
Results from REACH1, a Single-Arm Phase 2 Study of Ruxolitinib in Combination with Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Vs-Host Disease
This open-label, single-cohort, multicenter phase 2 trial demonstrates promising activity of oral single agent ruxolitinib as treatment for acute graft-vs-host disease. Overall response by day 28 was 54.9 percent, and best overall response rate was 73.2 percent. A phase 3 trial comparing ruxolitinib with best available therapy is underway.

10.) Abstract 1010
Treatment with AMG 420, an Anti-B-Cell Maturation Antigen (BCMA) Bispecific T-Cell Engager (BiTE®) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study
This FIH study demonstrates activity of bispecific T-Cell engagers (BiTEs) in multiple myeloma.  This class of drugs seems to have less toxicity than CAR-T type therapies with impressive response rates in a heavily pretreated MM population. As longer half-life BiTEs enter trials, it will be more convenient to dose the patients repeatedly with hopefully similar responses at therapeutic and tolerable treatment levels.