Dr Kim also found that patients with 5 or more karyotypic abnormalities or del(17p) had worse progression-free survival. She then ranked patients’ cytogenetic risk into low, intermediate, or high. In the best-case scenario that combined the prognostic score and cytogenetic risk, a low-risk patient had a 61% chance of progression-free survival and 75% chance of overall survival at 4 years. “Using this readily available information, oncologists can guide their patients to treatment options and know which patients would benefit from transplant and which should consider alternative therapies,” said Dr Kim.
Such a scoring system is helpful for doctors who are on the fence about recommending allogeneic transplants to patients, said Joseph Tuscano, MD, professor of medicine at University of California Davis Comprehensive Cancer Center in Sacramento. “This does a good job of predicting who would have a good outcome,” he said. “You only want to offer this risky therapy to those patients who have a good chance of being cured with the transplant, which can be very intensive and quite toxic.”
One study on long-term survival rates that was published in the Journal of Clinical Oncology in 2011 found that most deaths following these types of transplants occurred within the first 2 years as a result of relapse, acute or chronic graft-versus-host disease, infection, or other toxicities of the procedure.2 “This tool allows us to have more balanced discussions with patients regarding the potential risks and benefits of transplants,” said Dr Tuscano. “You wouldn’t want to take a risk of dying from complications if your chance of long-term survival is low.”
However, Dr Tuscano cautioned about the limits of the study, specifically about the fact that the patients’ median age was 58 years. “This data set doesn’t apply to most of our patients we see in the clinic who are in their late 60s,” he said.
Yet other physicians questioned the study’s usefulness, as Dr Kim analyzed patients who had undergone allogeneic transplants between 2008 and 2014, before the treatment landscape had changed dramatically. “These results come from a database when we didn’t have access to all these novel therapies,” said Nishitha M. Reddy, MD, associate professor of medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. “We have 3 different drugs that have been approved recently, and they’re very good in this subgroup with a 17p deletion. Now we use these drugs first before trying a transplant,” said Dr Reddy. “The challenge is to figure out how to prognosticate transplant patients in the era of novel agents.”
Indeed, transplants are considered a last resort, according to the National Comprehensive Cancer Network’s treatment guidelines. “Prior to the development of small-molecule inhibitors, allogeneic HCT was considered as an effective treatment option for patients with high-risk CLL,” it said, concluding that transplants were no longer a reasonable treatment option for refractory CLL or disease relapse within 2 years after initial purine analogue-based therapy and/or disease with a del(17p) or TP53 mutation.3
“Our patients are doing so well on these new treatments that very few patients are going for transplants these days,” said William Wierda, MD, PhD, CLL section head and center medical director for the department of leukemia at MD Anderson Cancer Center in Houston, Texas. “[Dr Kim’s] study is becoming applicable to fewer and fewer patients.”
He said the next wave of research for CLL patients should focus on trying combinations of drugs. “These new targeted drugs are very well tolerated, and more patients are getting into complete remission and have undetectable minimal residual disease,” said Dr Wierda, referring to a study published in July 2019 in the Journal of Clinical Oncology in which researchers found that 27 of 53 patients who took ibrutinib plus venetoclax were in complete remission a year later.4 “We didn’t see these kinds of remission rates with standard chemoimmunotherapies, and they appear to be durable,” he said. “We’re in a very hopeful era with a lot of good options.”
- Kim HT, Ahn KW, Hu Z-H, et al. Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients: Center for International Blood and Marrow Transplant Research Report [published online June 28, 2019]. Clin Cancer Res. doi: 10.1158/1078-0432
- Wingard JR, Majhail NS, Brazauskas R, et al. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011;29(16):2230–2239.
- National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Chronic lymphocytic leukemia/small lymphocytic lymphoma. Version 5.2019, May 23, 2019.
- 4. Hillmen P, Rawstron AC, Brock K, et al. Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: The CLARITY study [published online July 11, 2019]. J Clin Oncol. doi: 10.1200/JCO.19.00894