Precision Medicine and Immunotherapy Highlighted at ASH 2017ASH Highlights, Conference Correspondent, Web Exclusives
Atlanta, GA—More than 25,000 attendees converged on Atlanta during the middle of a rare winter snowstorm to attend ASH 2017, which featured nearly 5000 scientific abstract presentations ranging from cutting-edge advances in gene therapy and personalized medicine to practice-changing discoveries in immunotherapies.
Featured topics included the use of combination therapies in hematologic malignancies and 2 ASH-FDA symposia on new drug approvals for the treatment of acute lymphoid leukemia, non-Hodgkin lymphoma (NHL), and acute myeloid leukemia, as well as a late-breaking abstracts session that featured 6 studies with new data related to novel drugs with high clinical impact.
“With precision medicine being a major theme this year, we are excited to highlight the cross-cutting areas of genomics and immunology and the promise they offer to transform the way we care for our patients,” said ASH President Kenneth C. Anderson, MD, Program Director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Boston.
Several studies highlighted novel targeted cancer therapies being used to improve outcomes and quality of life for patients with rare, advanced, or difficult-to-treat hematologic malignancies. These included a phase 3 comparison of the investigational agent mogamulizumab with standard-of-care vorinostat (Zolinza) in patients with previously treated cutaneous T-cell lymphoma (see “Mogamulizumab, Anti-CCR4 Antibody, Improves Survival in Patients with Advanced Cutaneous T-Cell Lymphoma “). Median progression-free survival was 7.7 months for patients receiving mogamulizumab versus 3.1 months with vorinostat.
Also, patients with advanced Hodgkin lymphoma who received a multidrug regimen that included brentuximab vedotin (Adcetris) had a 23% reduction in the risk of disease progression, death, or the need for additional therapy, compared with patients who received the standard 4-drug first-line regimen for advanced Hodgkin lymphoma (see “A New Combination as First-Line Regimen in Advanced Hodgkin Lymphoma?“). These results represent the first successful effort in more than 30 years to improve outcomes of first-line treatment in patients with advanced Hodgkin lymphoma, without escalating chemotherapy to cause unacceptable toxicity.
In another important study, one-third of patients with previously treated chronic lymphocytic leukemia (CLL) had no detectable disease after 6 months of therapy with the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta)—both of which are approved for CLL as monotherapies—with no increase in the occurrence of tumor lysis syndrome (see “Ibrutinib plus Venetoclax Combo Elicits Impressive Responses in Relapsed Chronic Lymphocytic Leukemia“).
Three studies spotlighted the emerging role of immunotherapy with chimeric antigen receptor (CAR) T-cell therapies to achieve remissions in NHL, diffuse large B-cell lymphoma (DLBCL), and multiple myeloma.
Among 108 patients with refractory aggressive NHL, more than 50% were still alive at least 1 year after receiving a single infusion of the CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which targets the CD-19 protein frequently found on lymphoma cells. More than 1 year after infusion of CAR T-cells, 42% of patients remain in remission and 40% have no evidence of cancer (see “CAR T-Cell Therapy Makes Significant Inroads in Lymphoma: Kymriah and Yescarta Show Durable Remissions“).
And in a 6-month interim analysis of the JULIET trial, the overall response rate (ORR) was 37% and the complete response rate was 30% after a single infusion of tisagenlecleucel (Kymriah), another CAR T-cell therapy directed at CD-19, in adult patients with relapsed or refractory DLBCL. Twenty-six percent of patients had therapy on an outpatient basis, noted lead investigator Stephen J. Schuster, MD, Director, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia. Responders remain relapse-free without additional therapy, and median overall survival has yet to be reached (see “CAR T-Cell Therapy Makes Significant Inroads in Lymphoma: Kymriah and Yescarta Show Durable Remissions“).
Finally, a 1-time infusion of an investigational CAR T-cell therapy that targets BCMA—a protein found on most multiple myeloma cells—elicited an 86% ORR in 21 patients with relapsed or refractory disease after a median of 7 previous treatments, according to results from a phase 1 study. Among 18 patients who received higher, active doses of infused CAR T-cells, the response rate improved to 94%, with manageable adverse effects (see “CAR T-Cell Therapy Shows “Impressive” Results in Multiple Myeloma).
Phosphatidylserine, an Immune-Modulating Checkpoint, Ushers in the Next Wave of Immuno-Oncology Targets
The immune system recognizes and is poised to eliminate cancer but is held in check by a plethora of inhibitory pathways that regulate cellular immune responses.1 These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during antimicrobial immune responses, can be co-opted by cancer to evade [ Read More ]
Cellular therapy is becoming an attractive option for heavily pretreated patients with relapsed or refractory multiple myeloma. According to data presented at the ASCO 2020 virtual annual meeting, 2 chimeric antigen receptor (CAR) T-cell drugs have generated impressive rates of response that are sustainable.