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MCL: Event-Free Survival at 2 Years Bodes Well

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, ” Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”

Two Eras of Treatment

The current analysis by Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.

Favorable Prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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