This slide show features some of the top highlights on immunotherapies and other new agents in leukemia and lymphoma from the 2014 ASH Meeting.
References:
1. Moskowitz CH et al. The Aethera Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma. 2014 American Society of Hematology Annual Meeting. Abstract 673.
2. Stewart AK et al. Carfilzomib, Lenalidomide, and Dexamethasone vs Lenalidomide and Dexamethasone in Patients (Pts) with Relapsed Multiple Myeloma: Interim Results from ASPIRE, a Randomized, Open-Label, Multicenter Phase 3 Study. 2014 American Society of Hematology Annual Meeting. Abstract 79.
3. Armand P et al. Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma - Preliminary Safety, Efficacy and Biomarker Results of a Phase I Study. 2014 American Society of Hematology Annual Meeting. Abstract 289.
4. Moskowitz CH et al. PD-1 Blockade with the Monoclonal Antibody Pembrolizumab (MK-3475) in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Preliminary Results from a Phase 1b Study (KEYNOTE-013). 2014 American Society of Hematology Annual Meeting. Abstract 290.
5. Stein EM et al. AG-221, an Oral, Selective, First-in-Class, Potent Inhibitor of the IDH2 Mutant Metabolic Enzyme, Induces Durable Remissions in a Phase I Study in Patients with IDH2 Mutation Positive Advanced Hematologic Malignancies ). 2014 American Society of Hematology Annual Meeting. Abstract 115.
6. Ravandi F et al. Improved Survival in Patients with First Relapsed or Refractory Acute Myeloid Leukemia (AML) Treated with Vosaroxin Plus Cytarabine Versus Placebo Plus Cytarabine: Results of a Phase 3 Double-Blind Randomized Controlled Multinational Study (VALOR). 2014 American Society of Hematology Annual Meeting. Abstract LBA-6.
7. Goekbuget N et al. BLAST: A Confirmatory, Single-Arm, Phase 2 Study of Blinatumomab, a Bispecific T-Cell Engager (BiTE®) Antibody Construct, in Patients with Minimal Residual Disease B-Precursor Acute Lymphoblastic Leukemia (ALL). 2014 American Society of Hematology Annual Meeting. Abstract 379.
Patients with Hodgkin lymphoma who received brentuximab vedotin as consolidation therapy after an autologous stem cell transplantation (ASCT) lived significantly longer and without disease progression compared with those who received ASCT alone. The median progression-free survival was 43 months in the brentuximab vedotin arm compared with 24 months in the control arm (hazard ratio = 0.57;
P
= .001). The estimated 2-year progression-free survival rate was 54%, and the estimated 2-year overall survival rate was 88%.
Image source: Craig H. Moskowitz, MD, Memorial Sloan Kettering Cancer Center, New York.
[1]
Slide 2: Addition of Carfilzomib to Standard of Care Combo Delays Disease Progression in Multiple Myeloma-
Adding carfilzomib to a standard combination of lenalidomide plus dexamethasone in relapsed multiple myeloma increased median progression-free survival by 8.7 months. The median progression-free survival was 26.3 months in the triplet combination arm compared to 17.6 months in the control arm (hazard ratio = 0.69,
P
< .0001). The median duration of response was 28.6 months and 21.2 months in the experimental and control arms, respectively. Patients in both treatment arms had comparable adverse event and death rates due to therapy. The complete response rate was three times higher in the triplet therapy arm compared to the control arm (31.8% vs 9.3%).
Image source: A. Keith Stewart, MD, Mayo Clinic, Scottsdale, Arizona.
[2]
Slide 3: Immunotherapy Antibody Nivolumab Demonstrates Activity in Hodgkin Lymphoma-
Nivolumab, an anti–PD-1 immunotherapy antibody has demonstrated efficacy in relapsed, refractory Hodgkin lymphoma. These are the first nivolumab results in a hematologic cancer. Among 23 patients, many of whom had as many as three prior treatment failures, 20 patients (87%) responded to nivolumab therapy. This included 4 patients (17%) who had a complete response and 16 patients (70%) who had a partial response after a median follow-up of 40 weeks. Adverse events were similar to those seen in solid tumor patients and there were no life-threatening toxicities or deaths in the trial. Five patients (22%) had an adverse event of grade 3 or higher.
Image source: Philippe Armand, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts
.[3]
Slide 4: Anti–PD-1 Antibody Pembrolizumab Shows Activity in Hodgkin Lymphoma-
In the first pembrolizumab data in a hematologic cancer, results from a phase I trial of heavily pre-treated Hodgkin lymphoma patients, two-thirds of patients responded to the immunotherapy. Six patients (21%) achieved a complete response and thirteen patients (45%) had a partial response. Median time to response was 12 weeks and the median duration of response has not yet been reached. All patients in the trial had PD-L1 expression in their tumors. Grade 3 adverse events included axillary pain, hypoxia, joint swelling, and pneumonitis, each in a single patient. There were no grade 4 events or treatment-related deaths in the trial.
Image source: Craig H. Moskowitz, MD, Memorial Sloan Kettering Cancer Center, New York.
[4]
Slide 5: Activity of First-in-Class IDH2 Inhibitor in AML Validates IDH2 as Therapeutic Target-
A phase I study of AG-221, an oral, first-in-class inhibitor of isocitrate dehydrogenase 2 (IDH2), has validated IDH2 as a therapeutic target in
IDH2
-mutated hematologic cancers, including acute myeloid leukemia (AML). Of a total of 45 patients who could be evaluated for efficacy, 25 patients (56%) responded, including 6 patients who achieved complete responses. The most common adverse events were nausea, pyrexia, diarrhea, and fatigue. The most common serious adverse events were leukocytosis, disseminated intravascular coagulation, and tumor lysis syndrome.
Image source: Eytan M. Stein, MD, Memorial Sloan Kettering Cancer Center, New York.
[5]
Slide 6: Combination Therapy for AML May Be Useful as Salvage Therapy-
The 711-patient VALOR trial, a randomized, double-blind, placebo-controlled trial of vosaroxin plus cytarabine in patients with first relapsed or refractory acute myeloid leukemia (AML), did not reach its primary endpoint of a statistically significant improvement in overall survival. Median survival was 7.5 months in the experimental arm compared with 6.1 months in the cytarabine alone arm (hazard ratio [HR] = 0.865,
P
= .06). But, the combination may work as a salvage therapy as patients who did not receive a transplant had a statistically significantly higher overall survival (6.7 vs 5.3 months; HR = 0.809;
P
= .02).
Image Caption: Farhad Ravandi, MD, University of Texas MD Anderson Cancer Center, Houston, Texas.
[6]
Slide 7: Complete Molecular Response Achieved with CD19-Directed Immunotherapy-
A single cycle of a CD19-based immunotherapy, blinatumomab, resulted in complete minimal residual disease (MRD) response in 78% of patients with acute lymphoblastic leukemia (ALL). The phase II international BLAST study recruited patients with ALL who had had an allogeneic stem cell transplant. The primary endpoint of the trial was MRD response.
Image source: Nicola Goekbuget, MD, Goethe University Hospital, Frankfurt, Germany
