Reply to V. Procházka et al

Abstract

In their letter, Prochazka et al raise several issues as to the validity of our conclusion that in patients with relapsed or refractory follicular lymphoma, the presence of tumor cells in blood or bone marrow—as detected by BCL2/IgH major break point region polymerase chain reaction (PCR) at the end of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone induction therapy—is not predictive of progression-free survival (PFS). First, they suggest that we should have analyzed separately patients with clinical complete (CR) and partial remission (PR). We agree that this would have been a relevant subgroup analysis. Unfortunately, the four subgroups (PCRpositive CR, PCR-negative CR, PCR-positive PR, and PCR-negative PR) were too small to allow for a meaningful statistical comparison. However, as mentioned in our report, there was no difference between patients in clinical CR or PR with regard to the proportion of bone marrow (BM) or peripheral blood PCR negativity at the end of induction treatment (50% v 55%). This is clearly indicative of the compartmentalization effect and at least partly explains the lack of prognostic value of PCR status post induction treatment. Second, the authors state that our finding that PFS was not different between patients who converted to PCR negativity and those who did not is in contrast with previous publications by others. We agree and consider this to be an important message of our report. Prochazka et al mention two observations in our article that they consider to be supportive of the predictive value of PCR status. Their first consideration is based on our finding that there was highly significant improved PFS by rituximab maintenance in patients with postinduction PCR-negative BM, whereas the improvement was not significant in patients with PCR-positive BM (Figs 4A, 4B). In fact, there was a clear difference in the PCR-positive BM group, but this did not reach statistical significance because of limited numbers. However, highly significant improvement in PFS by rituximab maintenance was observed in both patients with postinduction PCR-negative blood and those with postinduction PCR-positive blood (Figs 4C, 4D). These observations do not change our conclusion that benefit from rituximab maintenance is independent of postinduction PCR status. Second, they mention our observation that patients who were still PCR positive at the end of maintenance treatment progressed rapidly after stopping maintenance therapy. In our opinion, this observation is not indicative of the predictive value of postinduction PCR status, but it is a strong argument for prolonging maintenance treatment.