Observation After Diagnosis Viable Strategy for Some Patients With MCL

Pau Abrisqueta, MD

Some patients with mantle cell lymphoma (MCL) can delay treatment without experiencing negative outcomes, according to findings from a population-based study of patients entered into the British Columbia Cancer Agency Lymphoid Cancer Database from 1998 to 2014.

Characteristics associated with deferred treatment included good performance status, no B symptoms, low LDH, non-bulky disease, non-blastoid morphology, and lower Ki67 values.

A total of 440 patients were evaluated, of whom 83% received early treatment and 17% were observed for ≥3 months.

At a median follow-up of 48 months, the median time to treatment in the observation group was 35 months (range, 5-79); 60 patients (80%) were observed ≥12 months without undergoing treatment, including 10 patients (13%) who did not require treatment for at least 5 years. Overall, 29 patients did not receive treatment, though 5 eventually experienced disease progression but were too frail for treatment. Median follow-up in the 24 patients without progression and who did not require treatment was 35 months.

Previous studies have suggested that a subset of patients with MCL can delay treatment after diagnosis. However, those results are based on small patient cohorts, so researchers have not been able to reliably identify patients with indolent MCL at the time of diagnosis. Investigators with the British Columbia Cancer Agency conducted this study to categorize the clinical and pathological characteristics and outcomes of patients with newly diagnosed MCL who underwent observation as their initial treatment strategy.

“Our study suggests that a sub- group of patients with MCL may be safely observed at diagnosis of the disease without negatively impacting their outcomes, including not only those patients with a non-nodal distribution, but also asymptomatic patients with low-burden nodal presentation and a low Ki67 score,” first author Pau Abrisqueta, MD, Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada, and coinvestigators wrote. “These data could give rise to a future randomized trial investigating the outcome with deferred versus immediate treatment in a prospectively defined group of indolent MCL patients.”

In the entire cohort, the median follow-up in living patients was 46 months (range, 0.5-158), with no difference between the observation and early treatment groups. The median overall survival (OS) after first-line therapy in observed patients (n = 46) was 34 months (range, 0.4-113.5). Median OS was significantly longer in the observation group than in the early treatment group (72 vs 52.5 months; P = .041).

In multivariable analysis, the treatment decision was not associated with OS [hazard ratio [HR], 0.804; 95% CI, 0.529-1.221; P = .306).

Clinical presentation was the only variable significantly associated with time to treatment (P = .012). All other factors, including MIPI and the Ki67 and the MCL35 assay, were not predictive in the observed population.

In the observation group, age at diagnosis, stage, LDH, and histological pattern did not impact OS. Clinical presentation (nodal, non-nodal, or gastrointestinal) and TP53 status by immunohistochemistry were the only factors associated with OS. Proliferation was not prognostic in the observed patients, unlike in the treatment group, although the number of patients in the high-risk groups for Ki67 and MCL35 assay was very small.

Researchers evaluated the impact of treatment initiation on OS in a multivariate Cox proportional hazards regression model together with other prognostic factors including MIPI risk categories (low vs intermediate vs high), stage (I/II vs III/IV), clinical presentation (nodal vs non-nodal) and blastoid morphology (blastoid vs non-blastoid). In this model, observation versus early treatment was not associated with OS (HR, 0.804; 95% CI, 0.529-1.221; P = .306).

“Ultimately, treatment deferral did not impact OS, and avoided unnecessary treatment in 24/440 (5%) patients,” Abrisqueta et al wrote.

Abrisqueta P, Scott DW, Slack GW, et al. Observation as the initial management strategy in patients with mantle cell lymphoma [published online June 27, 2017]. Ann Oncol. doi:10.1093/annonc/mdx333.