Although lymphomas were among the first cancers to be molecularly subtyped, she said, they still lag behind other cancers when it comes to using molecular information to improve treatment. Further along, she suggested, are lung cancers, where the development of targeted treatments, such as ALK inhibitors and checkpoint inhibitors, have brought big changes to therapy.
But in lymphoma, despite having a large number of targeted therapies available no one drug has emerged yet as superior for treatment. Among the drugs considered most widely studied, however, is ibrutinib, which works by blocking Bruton’s tyrosine kinase, a protein lymphoma cells use to survive.
The U.S. Food and Drug Administration already has approved this cell signaling inhibitor for several rare types of lymphoma and physicians now are awaiting results of a large DLCBL randomized trial, according to Dr Vose. In the trial, newly diagnosed patients with this cancer were divided by the original molecular classification of ABC or GBC, she said, then randomly assigned to receive either ibrutinib or a placebo in combination with chemotherapy.3
A number of other small molecules, such as P13K inhibitors, are undergoing testing, as well, not only in the frontline setting when patients are first diagnosed, but also after relapse. Relapse rates carry a wide range, Dr Vose said, ranging from fewer than 15% of patents to over 50%.
Ultimately, whether the NCI-led work can be readily duplicated or serve as a prototype for molecular refinements in other cancers will take time and resources, experts agree. Next-generation DNA sequencing is rarely done in clinical trials today for patient selection, said Julio Chavez, MD, an assistant member in the lymphoma section of the department of malignant hematology at Moffitt Cancer Center in Tampa, Florida. But the new classification should help guide physicians’ efforts to design such trials in the future, he wrote in an email.
As for solid tumors, opening a new molecular window on these cancers would be more difficult, given their heterogeneity and genetic burden, Dr Chavez said. Even though advanced sequencing technologies definitely can be applied to them, they tend to be more complex diseases than hematologic malignancies, he said.
Tycel Phillips, MD, a medical oncologist specializing in treating lymphoma at the University of Michigan Rogel Cancer Center in Ann Arbor, also offered a measured view of the new molecular insights into DLCBC .
“I do think we’re making headway against these cancers,” he said “But, in the upfront setting, we’ve not yet found anything better than R-CHOP,” the gold standard chemotherapy regimen physicians use in combination with a monoclonal antibody to first treat the disease.
Still, while the molecular refinement of DLCBC will have no impact on newly diagnosed patients right now, he said what’s been done “will change things going forth.”
- Schmitz R. Wright GW, Huang D, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018; 378:1396-1407. doi: 10.1056/NEJMoa1801445
- NCI study revises molecular classification for most common type of lymphoma. National Cancer Institute press release. April 11, 2018. https://www.cancer.gov/news-events/press-releases/2018/lymphoma-genetic-subtypes
- U.S. National Library of Medicine. A Study of the Bruton’s Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma. ClinicalTrails.gov Identifier: NCT01855750. Accessed May 30, 2018.