Josep Maria Ribera
Head of the Haematology Department at ICO Badalona
This is a multicentre, phase 2 clinical trial involving prestigious European groups with a long tradition in the treatment of childhood acute lymphoblastic leukaemia (ALL). Given the rarity of the KMT2A-rearranged ALL subtype, a phase 3 trial was not possible, so the results of this study were compared with those of previous studies in patients with the same type of ALL.
Previous evidence available in infants with LAL with KMT2A rearrangement was disappointing. In fact, this subtype is the one with the worst prognosis (50% survival) and where no treatment advances had been reported in the last 10 years. Hence the importance of the results of this clinical trial (90% survival), clearly superior to what was available until now, as is perfectly reflected in the published work. This was achieved by simply adding one cycle of blinatumomab to the classic chemotherapy treatment.
This small modification has led to a large improvement in survival, demonstrating the high efficacy of immunotherapy with the monoclonal antibody. The clinical implications of this are clear.
Limitations are cited by the authors in their study. There are mainly three. First, the small number of patients (30). Secondly, the relatively short follow-up (median 2 years). Finally, the fact that it is not a randomised study, i.e. comparing patients treated with and without blinatumomab within the same study.
These limitations are logical in the treatment of a very rare subtype of ALL. On the other hand, although the follow-up is short, it is a well-known fact that in ALL with KMT2A rearrangement, relapses, if any, occur early and would therefore be detected with the follow-up available in this study.
The results of this study apply only to a very small group of ALL occurring mainly in infants, representing 5% of all childhood ALL. The great merit in my opinion is that it places the survival of this group, characteristically with a poor prognosis, at the level of other subgroups of childhood ALL with a good or intermediate prognosis. Moreover, it demonstrates the great power of immunotherapy, with blinatumomab in this case, in the treatment of ALL. This is not unique to this subtype of ALL. The efficacy of this drug administered first line is also being demonstrated in adults.