Blood cancers

MCL2: prolonged remissions without survival plateau


The latest data from the long-running Second Nordic Mantle Cell Lymphoma (MCL2) trial suggests that the disease will not be eradicated by strategies that are currently considered first line treatment, experts say.

The 15-year updated results of the study involving 159 patients aged under 66 followed for a median of 11.4 years revealed that half of the patients were alive more than 12 years after the end of treatment and 40% were still in their first remission.

For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12.7 and 8.5 years, respectively.

The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups.

However, a continuous pattern of relapse and an excess mortality persisted even after long-term remission; furthermore, survival curves never reached a plateau, the Nordic Lymphoma Group noted in their paper published on the British Journal of Haematology.

The study authors said that even though they considered the Nordic regimen* as a “very good choice” they recommended inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.

“At present, the treatment of MCL is in transition with many novel targeted agents in development, and the challenge now seems to be how rather than if they should be incorporated in the first-line treatment,” they wrote.

One such agent was ibrutinib, which had produced impressive response rates in the relapse setting and had been included in the European MCL Network’s “Triangle” trial of untreated MCL patients.

“But until convincing data emerge, the standard-of-care remains an Ara-C containing induction plus rituximab, followed by high dose chemotherapy and ASCT,” they concluded.

Patients involved in MCL2 trial were newly diagnosed with stage II-IV MCL, all expressing cyclinD1 (CCND1) or positive for t(11;14) according to the World Health Organization criteria for MCL and were untreated at inclusion in the trial.

*The Nordic regimen involved alternating courses of maxi-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and high-dose Ara-C, 3 of each. Rituximab was co-administered on day 1 in cycles 4 and 5, and on days 1 and 9 in cycle 6. After an amendment in 2003, rituximab was administered also in cycles 2 and 3. A stem cell harvest was performed after cycle 6. Either BEAM (carmustine, etoposide, Ara-C, melphalan) or BEAC (carmustine, etoposide, Ara-C, cyclophosphamide) was used as a high-dose regimen before ASCT.

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