Frontline therapy in multiple myeloma: fast start for a long game
Mené au Royaume-Uni sur 583 patients atteints d'un myélome multiple récemment diagnostiqué, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité d'un traitement combinant cyclophosphamide, bortézomib et dexaméthasone avec intensification de doses et sans intensification, en fonction de la réponse au traitement d'induction initial à base de ces mêmes trois agents
Survival after diagnosis of multiple myeloma has been substantially improved in the past two decades owing to the availability of effective drugs administered in sequential phases, such as induction, autologous stem cell transplantation (ASCT) for eligible patients, maintenance, and salvage treatments at relapse. The bulk of evidence suggests that depth of response, regardless of how it is measured (either by standard response criteria based on serum or urine monoclonal protein detection or by more sensitive flowcytometric and molecular techniques in bone marrow), is correlated with subsequent clinical outcomes.1
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Moreover, minimal residual disease assessment has been recognised as a clinical and regulatory endpoint in clinical trials. Prospective studies comparing ASCT with therapies at conventional doses, tandem with single ASCT, and consolidation with no consolidation3
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have clearly confirmed the positive effect of late treatment intensification on clinical outcomes in transplant-eligible patients. However, the clinical value of maximising response during induction has not been extensively explored. The Myeloma XI trial reported in The Lancet Haematology by Graham H Jackson and colleagues6
has helped to fill this knowledge gap.
The Myeloma XI trial is a large, national study done in the UK including 3894 patients with newly diagnosed multiple myeloma. Jackson and colleagues6
report one of the three randomisation stages evaluating the clinical value of a response-adapted approach to induction therapy in this setting. The authors show a significant improvement of progression-free survival in patients who achieved partial or minimal response after first-line treatment with cyclophosphamide, lenalidomide or thalidomide, and dexamethasone and were then switched to an intensified induction with bortezomib, cyclophosphamide, and dexamethasone. This improvement in progression-free survival was observed in both, transplantation-eligible and ineligible patients. After bortezomib, cyclophosphamide, and dexamethasone, 123 (43%) of 289 patients improved depth of response, with 10 (3%) achieving complete response and 113 (39%) achieving very good partial response. Unfortunately, remission was evaluated only by standard serological criteria, and minimal residual disease data reporting is postponed by the authors to a subsequent publication. The benefit of bortezomib, cyclophosphamide, and dexamethasone was independent on age, International Staging System stage, and cytogenetic risk group and was persistent after ASCT in transplant-eligible patients. Toxicity was mainly haematological and manageable in all patients. No advantage in overall survival was observed 3 years after randomisation in the intensified induction group, probably due to the efficacious subsequent treatments patients received (eg, maintenance or salvage at relapse).
The Lancet Haematology , commentaire en libre accès, 2018