Page 286 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
AB
CD
Figure 3. Landmark progression-free survival analysis stratified by minimal residual disease evaluated at different time points.
(A) Overall minimal residual disease (MRD) at early restaging after 3 bendamustine rituximab courses (ER). (B) Overall MRD at end of treatment (EOT). (C) Overall MRD at 1-year follow-up (FU-1). (D) Peripheral blood MRD at ER. PFS: progression-free survival; overall MRD: at least 1 MRD-positive sample (either bone marrow or peripheral blood); MRD-: unmeasurable MRD.
PFS (Figure 3B), while no difference in PFS was observed between CR and PR groups (P=0.438; data not shown). Three MRD+ patients slowly converted to unmeasurable MRD- sta- tus, and seven CRu and one SD patient eventually met the criteria for CR at FU1 12 months after completion of treat- ment. None of the patients received off-protocol treatments or maintenance therapy. A speculative explanation for the spontaneous conversion to MRD- might be the gradual elim- ination of minimal subsets of residual neoplastic cells by the restored activity of the immune system after EOT. Accordingly, the MRD levels of these three patients were below 1x10-4 (namely 2, 2, and 3 copies/50,000 cells). In conclusion, the BRISMA study substantiates that BR chemoimmunotherapy accomplishes a swift and significant reduction in tumor bulk for patients with symptomatic SMZL, thereby facilitating notably high 5-year PFS and OS rates. Other retrospective studies have reported comparable PFS and OS rates with less toxic treatments.6;13 However, this phase II study with extended FU provides compelling evidence for consider- ing bendamustine-rituximab as an effective treatment for symptomatic SMZL patients.
Three other informative results come from the MRD analysis: i) our findings support the assertion that attaining MRD- af- ter just three courses of treatment is a promising indicator
of favorable long-term outcomes, even when monitored in PB.7-8,12 Though data are not yet mature enough to use MRD status in clinical decisions, it could help stratify patients in future trials. Furthermore, ii) integrating MRD results with response criteria is worth exploring due to the imaging lim- itations in detecting the disease in the spleen.14 Finally, iii) the incidence of additional cancers in this series aligns well with the cumulative incidence rate documented in existing literature.15 Consequently, we recommend conducting an SPC assessment before initiating a BR treatment and throughout the FU period, particularly in elderly patients.
Authors
Emilio Iannitto,1,2 Simone Ferrero,3 Côme Bommier,4,5 Daniela Drandi,3 Martina Ferrante,3 Krimo Bouabdallah,6 Sylvain Carras,7 Guido Gini,8 Vincent Camus,9 Salvatrice Mancuso,10 Luigi Marcheselli,11 Angela Ferrari,12 Michele Merli,13 Benoit Tessoulin,14 Caterina Stelitano,15 Kheira Beldjord,4 Giovanni Roti,16 Fabrice Jardin,8 Barbara Castagnari,17 Francesca Palombi,18 Lucile Baseggio,19 Alexandra Traverse-Glehen,20 Claudio Tripodo,2 Anna Marina Liberati,21 Margherita Parolini,22 Sara Usai,23 Caterina Patti,24 Massimo Federico,25 Maurizio Musso,1 Marco Ladetto,26 Emanuele Zucca27 and Catherine Thieblemont4,5
Haematologica | 109 July 2024
2300