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Deferred therapy may benefit some patients with mantle cell lymphoma
Deferring initial treatment for more than 90 days prolonged OS among certain patients with mantle cell lymphoma, according to a national cohort analysis.
Patients most likely to benefit from deferred treatment included those who were male, younger and had no comorbidities.
Jonathon B. Cohen
Most patients with mantle cell lymphoma receive aggressive, uniform treatment, without consideration of clinical or pathological risk factors. Intensive induction regimens, such as R-HyperCVAD, are associated with toxicity and may overtreat patients who could experience prolonged PFS and OS with a less intensive approach.
Study data have suggested patients who present with limited symptoms and indolent disease course can benefit from observation rather than immediate therapy.
Jonathon B. Cohen, MD, MS, assistant professor in the department of hematology and medical oncology at Emory University School of Medicine and medical director of infusion services at Winship Cancer Institute of Emory University, and colleagues used the National Cancer Data Base to evaluate the role of deferred therapy — treatment initiated more than 90 days following diagnosis — in 8,029 patients (73% male; 81% non-Hispanic white; 64% aged older than 60 years) diagnosed with mantle cell lymphoma between 2004 and 2011. Eighty-five percent of patients had stage III or IV disease at the time of diagnosis and 22% of patients had comorbidities.
Researchers classified the patients as from one of four regional groups: South (34%), Midwest (29%), Northeast (20%) and West (17%).
Six percent (n = 492) of patients received deferred initial treatment, with a median time to treatment of 121 days (range, 91-1,152). Seventy-two percent of this cohort was male, 60% were aged older than 60 years and 19% had comorbidities.
Patients who deferred treatment were more likely to be from the Northeast or West regions (P < 0.0001), to be treated at a high-volume teaching or research institution (P = 0.005), and to have stage I or II disease (P < 0.0001). These patients were less likely to have B symptoms at diagnosis, and results of a multivariate model showed absence of B symptoms was the strongest predictor of deferred therapy (OR = 1.67; 95% CI, 1.4-2). Other predictors of improved OS with deferred therapy included extranodal primary site of presentation (OR = 1.24; 95% CI, 1-1.5) and Hispanic race (OR = 1.44; 95% CI, 1.1-2).
For the entire study population, receipt of deferred therapy predicted improved OS (HR = 0.79, 95% CI, 0.7-0.9). This association persisted among patients with advanced disease (OR = 0.76, 95% CI, 0.6-0.9), who researchers acknowledged represented 85% of the cohort.
Multivariate analysis showed that in the deferred-treatment group, male sex (OR = 0.7, 95% CI, 0.5-1), age younger than 60 years (OR = 0.48, 95% CI, 0.3-0.7) and absence of comorbidities (OR = 0.44, 95% CI, 0.3-0.7) predicted improved OS.
The lack of detailed lymphoma-specific clinical data — such as Mantel Cell Lymphoma International Prognostic Index — may have limited the study results, according to the researchers. Other study limitations include limited availability of treatment-specific data and cause of death in the National Cancer Data Base.
“Although specific patient data are limited in this series, we believe that the improved OS of patients who deferred therapy reflects predominantly a subset of patients with lower risk disease and not the adverse effects of therapy-related toxicity,” Cohen and colleagues wrote. “Therefore, we support current guideline recommendations and continue to advocate immediate treatment for patients who are candidates for therapy and have symptomatic disease at the time of diagnosis.” – by Nick Andrews
Disclosure: Cohen reports grants and personal fees from Bristol-Myers Squibb, Celgene, Janssen, Novartis, Millennium/Takeda and Pharmacyclics outside of this study.
Perspective
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Abimbola Farinde, PhD
Mantle cell lymphoma is a relatively rare cancer of the lymphoid cells. It was given this name because the cancer cells arise from the outer rim — or “mantle” — of the lymphoid cells surrounding a lymphoid follicle.
Public awareness of this form of cancer increased around 2014 when Andrew Madoff — the last surviving son of investment manager Bernard Madoff, convicted of running the largest Ponzi scheme in history — experienced a recurrence of the cancer and eventually died of the disease. This led to increased research interest, which shaped the landscape of future treatment.
Mantle cell lymphoma accounts for approximately 2% to 10% of all non-Hodgkin lymphomas. Treatment can include a variety of chemotherapeutic and targeted agents. The use of an intensive induction regimen has been shown to prolong life, but it also can be associated with toxicity and, at times, overtreatment of patients who may experience prolonged PFS and OS with less intensive approaches.
Cohen and colleagues sought to examine the OS rate among 8,029 patients who were divided into two groups. One group received immediate therapy; the other received deferred therapy, with more than 90 days elapsing between diagnosis and treatment initiation.
Some may argue that deferring treatment in patients with mantle cell lymphoma may cause more harm than good for patients with this already-rare and potentially high-risk form of cancer, but the researchers sought to determine if deferred therapy would be safer compared with the use of an induction regimen.
At times, patients with mantle cell lymphoma can be treated uniformly without consideration for other factors, such as clinical or pathologic risks, according to the researchers.
But the potential use of deferred therapy can become another viable treatment option in the future.
For deferred therapy to be initiated in specific patients, additional studies are needed to determine which individuals would be the best candidates based on risk stratification. In the meantime, the decision as to the best course of therapy should be made based on a comprehensive discussion between providers and patients, as well as what current evidence suggests are the most effective treatment options.
Disclosure: Farinde reports no relevant financial disclosures.