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Early relapse predicts poor outcomes in patients with mantle cell lymphoma

BySavannah Demko

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David Bond

ORLANDO — Patients with mantle cell lymphoma who relapse within 6 months of frontline therapy experienced poor outcomes with current salvage therapies, according to results presented at ASH Annual Meeting and Exposition.

“Patients with very early relapse of mantle cell lymphoma experience poor outcomes with standard therapies, supporting the development of new treatment approaches – including CAR-T treatment – in this patient population,” David A. Bond, MD, hematologist from The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, told HemOnc Today.

Bond and colleagues compared outcomes after frontline treatments in a large cohort of patients with mantle cell lymphoma (MCL) and described outcomes by class of second line treatment for patients with primary refractory disease.

Using data from patients treated between 2000 and 2017, researchers estimated overall survival (defined from time of first progression) and secondary progression free survival (defined from first progression to second progression or death. The investigators categorized patients into:

• primary refractory – refractory disease to frontline therapy or progression of disease (POD) within 6 months of frontline therapy;
• POD24 – POD between 6 to 24 months of therapy; and
• POD > 24 – POD beyond 24 months.

In frontline therapy, intensive treatment was defined as high dose cytarabine and/or autologous stem cell transplant in first remission, and salvage therapy was classified as chemoimmunotherapy (CIT) for patients treated with CIT alone, BTK inhibitor for those treated with a single agent or in combination, and lenalidomide/bortezomib for those treated with one or both agent +/- anti-CD20 therapy, according to the abstract.

Overall, 457 patients with mantle cell lymphoma relapsed and were included in analysis (median follow-up = 2.6 years after first progression). Of these, 14% of patients were primary refractory, 34% had POD 24, and 53% had POD > 24.

Primary refractory patients had a median overall survival of 1.3 years, those with POD 24 had a median overall survival of 3 years and those with POD > 24 had a median overall survival of 8 years (P < .0001), according to the results.

After comparing median secondary progression free survival by time to POD, the researchers reported that median secondary progression free survival was 1 year (95% CI, 0.4-1.3) for primary refractory patients, 1 year for POD 24 and 2.3 years for POD > 24 patients (P < .0001).

Median overall survival was higher for primary refractory patients who received less intensive treatment than those who received intensive treatment (2 years vs. 0.9 years; P = .33). For patients who had POD 24, median secondary progression free survival and overall survival were both shorter following intensive treatment compared to less intense treatment (0.8 year vs. 2 years; P = .0003 and 2 years vs. 6.8 years; P = .05).

Analyses revealed that primary refractory and POD 24 were linked to inferior overall survival (HR = 7.7; 95% CI, 3.9-15.1 for primary refractory and HR = 2.5; 95% CI, 1.4-4.5 for POD 24).

“Of the currently available treatment options for relapsed mantle cell lymphoma, inhibitors of BTK appear to be associated with longer remission for patients with very early relapse compared with other standard treatment classes,” Bond told HemOnc Today.

Among patients with primary refractory mantle cell lymphoma, median secondary progression free survival and overall survival were 1.2 and 2.4 years for BTK inhibitor; 0.5 and 1.1 years for CIT; and 0.3 and 1.9 years for lenalidomide/bortezomib as second line therapy, according to the abstract.

“These data further establish the prognostic significance of duration of first remission in the non-Hodgkin's lymphoma sub-type mantle cell lymphoma,” Bond said. – by Savannah Demko

References:

Bond DA, et al. Abstract 753. Presented at: ASH Annual Meeting and Exposition; December 7-10, 2019; Orlando, Florida.

Disclosures: Bond reports no relevant financial disclosures.