ASH 2021 | The impact of COVID-19 on ALL

We, in this last year and a half, in Italy, we’ve carried out a number of studies on COVID, on the impact of the pandemic on the management of hematological malignancies. And this has been done in Italy through networks that we set up years ago that are called campus, campus on given disease.

And in fact, the first one that we activated some six years ago is a campus on ALL involving, more or less, all centers in Italy dealing with ALL. But then there was a campus on CLL, a campus on CML, and in the framework of these campuses we did studies on the impact of COVID.

Now, in Italy the pandemic hit very heavily at the beginning of 2020, and in fact, we had the first lockdown was started on March 8th, 2020. So we did a number of surveys over this period to see how COVID, how the pandemic, had impacted on the management of hematological malignancies, and we published a number of papers on this. So at ASH we have an oral session, in fact, and Sabina Chiaretti presented data on the last survey that we carried out throughout this campus, LL network, on ALL.

We did already one study, and in fact we published the first report in Blood last year, and that was in Philadelphia-positive ALL, but there was a very low incidence of COVID in Philadelphia-positive patients. Now we extended this over more than a one year effect of the pandemic, which I told you started in February last year, and we put the data together on a large number of ALL sub-cases followed in different countries. And we showed, to summarize, that overall the incidence of COVID positivity of patients, and developing COVID infection was, how can I say, not that high. In fact, I would say the incident was not higher than the general population. Which is of interest this, because obviously you’re talking about disease where there is… Obviously the treatment has impact on immune system.

But if I expand this towards the data on CLL and CML, we didn’t see a very high incidence of positivity within diseases. Now that opens some interesting considerations. And one could be that in hematology centers we’ve been used to using measures that have been advocated for in a pandemic, so all patients and families are well aware that they should be using masks, that’s even before the pandemic, for years, they use masks, that they should repeatedly wash their hands, patients and family members, and that you don’t have to stay in a crowded area.

So all these measures that have been implemented for COVID pandemic, are measures we routinely have implemented in hematological patients, and centers, for years and years, so it’s nothing that we had to change. So I think that is something that has helped to reduce, or contain, the infection, and that I think is of some interest.

Now, going back to the ALL, that is the matter of this presentation, what can I add? I can add that the mortality rate that was obviously there, I think it was 11%, remembering off by heart, which is acceptable in a given setting. And I think one piece of information that is valuable to say, is that the subset of ALL, which was less affected in the sense of management… because in all the studies we did we tried to see how the COVID not only had an impact on infecting patients, but also in the management disease. Did you delay treatment? Did you stop treatment? And many other considerations which I don’t have time to cover. And this has been observed, obviously, to some extent.

Now in ALL where, as you can imagine, stringency of treatment is a key point, we’re talking about acute leukemia, if we want to try to cure disease we have to try to be stringent on the timing of treatment, no delays as much as possible.

Now in doing sub-analysis in ALL we found of interest, although not unexpected, but the subgroup patients that was less affected by COVID was patients that were Philadelphia-positive, so the Ph+ ALL, which in adults is the most frequent genetic subgroup. Now this is particular interesting because Ph+ ALL are managed with tyrosine kinase inhibitors. And in fact, us, as in Italy, for the last 15, 18 years, we’ve been treating Ph+ ALL in adults without systemic chemotherapy and induction. So patients are identified as Philadelphia-positive or negative within one week of diagnosis, that’s when they take steroid for one week. And the patients who are positive, as I said, for between 15 and 20 years, they’ve been getting a tyrosine kinase inhibitor and steroids alone, no chemotherapy and induction, first hematin, then dasatinib, and ponatinib, whatever.

Now, at the time of the pandemic we had opened our last protocol, which then closed, which were based not only in induction with a TKI which dasatinib plus steroids, but it was also based on a consolidation without chemotherapy, again, with immunotherapy, with a bispecific monoclonal blinatumomab, which targets CD19 on lymphoblastic cells, but also activates via CD3 the T-cells of the patient, so a form of immunotherapy.

So this means that the patients in protocol were receiving 84 days of dasatinib, plus two to five cycles of blinatumomab, which means between four and six months without systemic chemo. And part of the treatment can be done at home. So this was extremely valuable, even at a pandemic phase, because this reduced the number of days in hospital, and no chemotherapy during the induction consolidation. And in fact, if we tailor this to the results observed, the subset, as I mentioned, that was less affected by COVID, was exactly the Philadelphia-positive ALL. That underlying now again, the validity of not using chemotherapy in induction, and maybe even in consolidation.

And the data, I mean, we are not updating them at ASH this year, the data on the protocol was published in the New England Journal exactly one year ago, but we update them at DHA in July, and they look very consistent so far. So that has been valuable, even for managing patient during the pandemic.