ESH MM 2018 | Continuous or fixed-duration therapy in multiple myeloma?

The 4^th International Conference on Multiple Myeloma, organized by the European School of Haematology (ESH), took place on 5–7 of October 2018 in Mandelieu, France. The conference not only offered the opportunity to learn about current clinical practice and established guidelines but also to hear different views on hot topics in multiple myeloma (MM).

A debate that took place during the conference addressed the arguments for and against continuous versus fixed-duration therapy in newly diagnosed (ND) MM.

Thierry Facon from the University Hospital of Lille, France, supported the idea that continuous therapy should be the standard of care, based on results from several clinical trials: the Myeloma XI study has shown that maintenance therapy with lenalidomide is associated with a significantly longer median progression-free survival (PFS) compared to observation only; the HOVON-65/GMMG-HD4 trial showed that bortezomib maintenance favours patients with del17p; the ALCYONE trial has revealed superior PFS in patients treated with daratumumab in combination with bortezomib/melphalan/prednisone (VMP) compared to those treated with VMP alone, due to the maintenance treatment with daratumumab; the FIRST trial showed that NDMM patients ineligible for ASCT, who achieved complete or very good partial response and received continuous treatment with lenalidomide/dexamethasone (Rd), had a significantly longer PFS compared to those treated with Rd for a fixed duration of 18 cycles (Rd18).

Jesús San Miguel from the University Clinic of Navarra in Pamplona, Spain, did not support continuous nor fixed-duration treatment, but individualized-duration therapy, highlighting that continuous is not the same as prolonged treatment. There are several drawbacks to continuous treatment. These include: toxicity; high cost; and the trial design that usually compares maintenance with no treatment at all, rather than with a fixed-duration treatment. Moreover, results from clinical trials do not show a difference in overall survival (OS) after one or a maximum of two years maintenance therapy. Continuous therapy does not take into account prior response to treatment or the unique biological characteristics of each patient, such as the cytogenetic or monoclonal gammopathy of undetermined significance (MGUS) profile or the immune signature. It can be argued that after two years of heavy treatment, maintenance therapy is unlikely to benefit patients who have achieved partial response but may benefit those who have achieved complete response rates. The ideal scenario would be to adapt treatment options to match individual needs. If a patient has achieved a less than very good partial response (≤VGPR), she/he should be offered the option to change treatment rather than continue with the maintenance therapy.

The main conclusion of the debate was that both continuous and fixed-duration therapies should be considered and the best option will be a personalized one dependent on each patient’s disease features and personal needs.

References:

1. Thierry Facon. Continuous therapy. 4^th International Conference in Multiple Myeloma, European School of Haematology (ESH), Mandelieu, France.
2. Jesús San Miguel. Fixed duration. 4^th International Conference in Multiple Myeloma, European School of Haematology (ESH), Mandelieu, France.