Vaccination response to pneumococcal antigen as novel predictor for successful tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia.

Achieving treatment-free remission (TFR) is a new goal in the management of
chronic phase chronic myeloid leukemia (CML). Several studies have demonstrated
that approximately 40 to 50% of patients in sustained molecular remission can
discontinue their tyrosine kinase inhibitor (TKI) medication without leukemic
relapse (Mahon et al. STIM-trial; Saussele et al. EUROSKI-trial). Further
investigation is needed to better predict which patients will achieve a
sustained TFR in order to select the right patients and the right time for a
TKI discontinuation attempt.

Although cellular immune responses against cancer-associated antigens have
clearly been established, the humoral immune system also contributes to tumor
immune surveillance and therefore may contribute to sustained TFR in CML.
Patients with CML under TKI treatment have reduced responses to pneumococcal
vaccination in approximately 60% of cases (De Lavallade et al; Rajala et al).
This percentage corresponds to the percentage of patients who relapse after TKI
discontinuation. Although this may be a coincidence, in view of the lack of
clear cellular immune parameters predicting successful discontinuation, the
humoral immune system may indeed play an important role in maintaining
remission after TKI discontinuation.

To assess whether an adequate response to pneumococcal antigen, as a marker of
overall humoral immune system reactivity, predicts sustained TFR.

An adequate response to pneumococcal antigen will be defined as achieving
anti-pneumococcal IgG levels of > 1,0 ug/ml for >10 included serotypes.
Sustained TFR will be defined as major molecular response (MMR; BCR-ABL1 <
0.1%IS) at 12 and 24 months.

Multicenter, prospective, open-label, uncontrolled observational study

The vaccine itself has proven to be effective and safe, although, like almost
every vaccine, it may cause pain during injection and it may induce local
reactions at the injection site and mild fever (>10%), with more serious
reactions e.g. anaphylaxis being rare (<<0.01%).

To monitor the immune response a blood sample will be taken at two different
time points (approximately 50ml per taking), during which the subject may
experience some pain. It can induces a local (usually mild) hemorrhage with
soreness at puncture site.

Finally, the subject may experience some burden of the extra time lost to two
extra visits planned for the study.

In view of the safety profile of the vaccine, and the importance of better
prediction of success of stopping in the CML patient population in general, the
possible side-effects of administration are deemed acceptable risks.