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 10 abstracts the most compelling, clinically relevant and potentially transformative to the practice:
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1) Late-Breaking Abstract No. 6
KTE-C19 are chimeric antigen receptor expressing autologous T (CART) cells engineered to attack CD19+ B cells. In this planned analysis of a phase 2 multicenter trial of KTE-C19 to treat patients with refractory DLBCL, the objective response rate (ORR) was 76 percent with 47 percent complete response (CR), which met the primary endpoint (P < 0.0001). For a second cohort of 11 patients with transformed or primary mediastinal B-cell lymphoma, ORR was 91 percent with 73 percent CR. Adverse events were primarily cytokine-release syndrome (grade ≥ 3 in 13 percent) and neurologic events (grade ≥ 3 in 29 percent). The peak of CART expansion, at 7-14 days post infusion, correlated with ongoing CR. This trial demonstrates activity of KTE-C19 CART cells in refractory DLBCL and that this technology can be safely utilized at multiple centers.
2) Abstract No. 975
In a phase 1b, open-label, dose-escalation study, 66 patients with relapsed/refractory multiple myeloma (MM) received venetoclax, a potent, selective, oral small-molecule inhibitor of BCL-2, with bortezomib and dexamethasone. The overall response rate for all evaluable patients was 68 percent, and 40 percent achieved a very good partial response or better. Response rates were most prominent in patients who had disease that was nonrefractory to bortezomib (overall response rate of 89 percent). Clinical responses were also similar in patients with t(11;14) MM and without t(11;14) MM. The novel combination of venetoclax, bortezomib and dexamethasone appears to be promising therapy for patients with relapsed/refractory MM and is presently undergoing additional investigation in clinical trials.
3) Late-Breaking Abstract No. 5
In this randomized, open-label, phase 3 study, 311 patients with myelofibrosis and thrombocytopenia were randomized to receive two different schedules of the oral tyrosine kinase inhibitor pacritinib or best available therapy. Patients receiving pacritinib were significantly more likely to have a reduction in spleen size, reduction in red blood cell transfusion needs, and improvement in total symptom score than those receiving best available therapy, but with no improvement in overall survival. Pacritinib is on full clinical hold by the FDA as of Feb. 2016, based on concerns around excess deaths and cardiac and hemorrhagic events in PERSIST-1.
4) Abstract No. 1
The SUSTAIN study was recently published in the New England Journal of Medicine simultaneously with its presentation at ASH. Crizanlizumab (fka SelG1) is humanized anti-P selectin antibody that blocks platelet-leukocyte interactions, as well as interactions of activated endothelial cells with sickled red cells. Patients with sickle cell disease were randomized to high- or low-dose crizanlizumab or placebo with treatment administered 14 times over a period of 52 weeks. The median rate of crises per year was 1.63 with high-dose crizanlizumab compared to 2.98 with placebo (P = 0.01). In addition, the median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (P = 0.001), as was the median time to the second crisis (P = 0.02). Overall, the median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab compared with 2.91 with placebo (P = 0.02). Side effects occurring in at least 10 percent of the treatment groups with frequency at least twice those of the placebo group included pruritis, nausea, arthralgia, chest pain and diarrhea. Crizanlizumab significantly reduced the incidence of painful crises in patients with sickle cell disease with a relatively low toxicity profile.
5) Abstract No. 3
A major obstacle in adeno-associated virus (AAV) gene therapy for hemophilia B has been the development of a capsid-specific immune response. SPK-9001 utilizes a bioengineered AAV capsid (Spark100) with liver-specific tropism. The expression cassette is a codon-optimized, single-stranded transgene encoding Factor IX (FIX) Padua, a naturally occurring FIX variant with about eightfold greater specific activity compared to wild-type FIX. The prevalence of neutralizing antibodies to Spark100 among sampled hemophilia B sera was 40 percent. In this study, seven patients with antibody titers to Spark100 of 1:1 or less were infused with SPK-9001 at a dose of 5 x1011 vg/kg. These patients achieved median FXI:C (FXI coagulant) levels of 32.3 ± 6.5 percent without immunosuppression or evidence of a cytotoxic immune response. Four patients were able to stop after SPK-9001 treatment without breakthrough bleeding. No patients developed a FIX inhibitor. These results demonstrate the highest and most sustained levels of FIX:C after FIX gene transfer, and obviate the need for FIX infusions.
6) Abstract No. 469
The results of this phase 3 randomized trial comparing DA-EPOCH-R with the standard R-CHOP have been long awaited. Fewer events than expected have occurred, in part because only 35 percent of patients had high risk IPI (3 to 5). With median follow-up now more than 5 years, the IDMC recommended data release. The data show no differences in ORR, CR or in the primary endpoint of event-free survival (EFS) (3-year: 79 vs. 1 percent; 5-year: 68 vs. 69 percent). DA-EPOCH-R did cause more grade ≥ 3 thrombocytopenia (65 vs. 11 percent), febrile neutropenia (35 vs. 17 percent) and neuropathy (sensory: 14 vs. 2 percent; motor: 8 vs. 1 percent). Unfortunately, no analysis by cell of origin, MYC expression or translocation was presented. R-CHOP still remains the standard initial therapy for DLBCL.
7) Abstract No. 901
In this study, 754 patients with AML < 60 years were randomized to receive induction therapy with IA, IA plus the histone deacetylase inhibitor vorinostat (IA+V), or standard daunorubicin and Ara-C (7+3). There were no significant differences in EFS, relapse-free survival (RFS) or overall survival (OS) among all three arms. By cytogenetic or molecular group, there were no differences in outcome for any standard risk subset, although patients with favorable cytogenetics had significantly better EFS, RFS and OS with standard 7+3 therapy compared to IA arms (all P ≤ 0.015). The suspected cause is lower doses of Ara-C being given in the postremission setting for nonstandard therapies.
8) Abstract No. 787
In one of the largest trials (821 patients) to assess the safety of stopping TKI therapy for chronic myeloid leukemia, study participants who had taken a TKI for more than 5.8 years before stopping were significantly less likely to experience relapse within the first six months (relapse occurred in 34.5 percent of these patients) compared to those on the therapy for a shorter duration (57.4 percent). All participants had a stable, extremely low level of detectable leukemia markers for at least one year before TKI cessation. After stopping TKI therapy, 62 percent showed no evidence of leukemia recurrence at six months, and half (52 percent) showed no recurrence at 24 months. The question remains whether stopping TKIs should become standard in subsets of CML patients, and whether those who stopped were able to regain the durable remission with restarting TKIs.
9) Abstract No. 590
This phase 1b study included 42 patients who were administered the monoclonal antibody vadastuximab talirine along with standard chemotherapy. Patients showed no evidence of increased toxicity or mortality, and the rates of adverse effects were similar to those expected with standard chemotherapy alone. A higher-than-expected portion of patients achieved remission after a single round of treatment. A total of 78 percent of patients achieved remission, with 60 percent achieving complete remission (CR) and 18 percent achieving remission with incomplete blood count recovery. In addition, highly sensitive tests showed many patients had no evidence of the disease 28 days after starting treatment, suggesting the drug may lead to a deeper complete remission than standard chemotherapy alone.
10) Late-Breaking Abstract No. 1
A phase III trial conducted by the Blood and Marrow Transplant Clinical Trials Network investigated the role of post-transplant consolidation in 758 transplant-eligible patients with MM. Patients receiving upfront therapy were randomized to single melphalan autoHCT, tandem melphalan autoHCT, or single melphalan autoHCT followed by four cycles of consolidation with lenalidomide, bortezomib and dexamethasone (RVD). All arms included lenalidomide maintenance until disease progression. There was no significant difference in the primary objective of 38-month progression-free survival among the three arms. Similarly, the probability of overall survival and disease progression at 38-months was comparable. Single melphalan autoHCT followed by lenalidomide maintenance remains the standard of care as part of upfront treatment of MM. There is no benefit to adding RVD consolidation or a planned second autoHCT.
First-of-its-kind research investigates the viability of standard screening to reduce the burden of late-stage cancer diagnoses
Study demonstrates ability to reduce patients’ reliance on phlebotomies to stabilize hematocrit levels
Findings highlight an association between obesity and an increased incidence of moderate-severe disease
Cleveland Clinic Cancer Institute takes multi-faceted approach to increasing clinical trial access
Key learnings from DESTINY trials
Gene editing technology offers promise for treating multiple myeloma and other hematologic malignancies, as well as solid tumors
Study of 401,576 patients reveals differences in cancer burdens as well as overall survival
Enfortumab plus pembrolizumab reduced risk of death by 53% compared with platinum-based chemotherapy
