Considerations for treatment sequencing in B-ALL

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Published: 23 Jan 2020
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Prof Nicola Gökbuget - Universitätsklinikum Frankfurt, Frankfurt, Germany

Prof Nicola Gökbuget speaks to ecancer at the 2020 ALL Assembly meeting in Frankfurt about the considerations for treatment sequencing in patients with B-cell acute lymphoblastic leukaemia (B-ALL) when treated with immunotherapy.

She describes the various immunotherapeutic options that are available for this disease type, including blinatumomab and inotuzumab - which both lead to better response rates compared to standard chemotherapy and should be the treatment of choice for early relapse/refractory patients.

However, Prof Gökbuget states that for patients who relapse later, there is currently a lack of data for both agents.

She discusses the challenge of choosing between blinatumomab and inotuzumab and which patient populations will benefit the most.

 

The topic of my talk was treatment selection with the new immunotherapies and antibody therapies, sequencing and combination. In some countries we have now the opportunity to choose between three options, which is blinatumomab, inotuzumab and the CAR T-cells, CAR T-cells but only in patients up to the age of 25. The question is now how we decide on the sequencing, particularly in relapsed refractory ALL.

I spoke about the results for the different compounds because this gives us some arguments for decision making. For example, one important thing is that both inotuzumab and blinatumomab lead to better response rates compared to standard chemotherapy so the treatment of choice, at least in early and refractory relapses of ALL with B-precursor subtype would be either inotuzumab or blinatumomab. For later relapses we don’t have data for both compounds and also we don’t have enough data for extramedullary relapses.

Then if we have this type of relapse, early relapse, the question is now how to decide between inotuzumab and blinatumomab. There is one important thing that blinatumomab has a lower response rate if it is used in patients with high leukaemia burden. The cut level was around 50% so this is not a safe cut level but at least gives the indication. For inotuzumab we only know that the data were generated in patients who did not have a peripheral blast count above 10,000. So if we have a patient with a high leukaemia burden probably inotuzumab would be preferable compared to blinatumomab or any way to reduce the tumour load before blinatumomab, for example by giving a prephase treatment to reduce the leukaemia load. Or maybe in the future something which has not been done so far but can be done in clinical trials is to combine both approaches, give inotuzumab to reduce the tumour load and then blinatumomab to completely eradicate the ALL which would also have the advantage that there’s a longer interval between inotuzumab and the often subsequent stem cell transplantation and thereby maybe avoid some of the inotuzumab toxicities.

The key message is that the treatment therapy has changed so at the time-point of relapse you have to immediately consider the best option for the patient, not try some chemotherapy and maybe bring the patient in a poor condition acquiring, for example, fungal infections or something like this. First think about the strategy and, if possible, a really experienced centre should be consulted in order to plan the treatment. You should not forget that even with the new compounds the median survival of relapsed ALL is 7.7 months and we need to improve that. Therefore we should not just try something but to have a clear-cut strategy.

Another issue which occurs in the centres who have a luxury situation, in that they have CAR T-cells and blinatumomab available, the question is then how to decide. Of course the advantage of blinatumomab is the readily available compound which works very well also in patients with low tumour burdens, this is the ideal situation for blinatumomab. The advantage of CAR T-cells would be that it works apparently also in the extramedullary setting and that it could be an option for long-term outcome in patients who have a relapse after transplant. Because a second transplant usually has rather poor results and therefore many colleagues say at least a relapse after transplant should be an indication to consider CAR T-cells, either those with marketing authorisation or also to refer the patient to a clinical trial because in all countries clinical trials are ongoing. Also academic CAR T-cells and I think we should take that into account.