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. 2024 Dec;103(12):5861-5870.
doi: 10.1007/s00277-024-06130-y. Epub 2024 Dec 12.

In patients with follicular lymphoma, delayed-onset neutropenia induced by anti-CD20 monoclonal antibodies frequently occurs during maintenance therapy and is preferentially associated with obinutuzumab

Nashwa Fadaos  1 , Yossi Ben Dor  1 , Tehila Azoulay  2 , Ronit Leiba  3 , Nurit Sharon-Horesh  4 , Tsofia Levi  4 , Netanel A Horowitz  1   4 , Inna Tzoran  1   4 , Noa Lavi  1   4 , Ofrat Beyar-Katz  1   4 , Eldad J Dann  1   4 , Tsila Zuckerman  1   4 , Shimrit Ringelstein-Harlev  5   6
Affiliations

In patients with follicular lymphoma, delayed-onset neutropenia induced by anti-CD20 monoclonal antibodies frequently occurs during maintenance therapy and is preferentially associated with obinutuzumab

Nashwa Fadaos et al. Ann Hematol. 2024 Dec.

Abstract

The prevalence of anti-CD20 monoclonal antibody (MoAb)-associated delayed-onset neutropenia (DON) varies between 8 and 27%. Despite the wide use of MoAbs as maintenance in follicular lymphoma (FL), data regarding DON occurrence and clinical consequences are limited. This study assessed DON prevalence, severity and risk factors in FL patients during maintenance. Data were retrieved from electronic medical records of FL patients treated at Rambam between 2006 and 2021. The maintenance cohort included 155 patients receiving 165 treatment courses; the non-maintenance cohort included 58 patients receiving 67 courses. Median time on maintenance was 1.81 ± 0.28 years. During maintenance, 23.2% of patients developed DON, with 13.8% experiencing at least one recurrent event. In the non-maintenance cohort, 29.3% developed DON, with 38.8% recurrence. Median time from maintenance initiation to the first neutropenic episode was 5 (1.25-12) months, whereas in the non-maintenance cohort, DON occurred earlier [1.9 (0.97-3.71) months; p = 0.06]. The only DON risk factors in patients on maintenance were induction with the obinutuzumab/bendamustine combination [odds ratio (OR): 4.546 (95%CI = 1.419-14.563); p = 0.011] or obinutuzumab maintenance [OR: 3.138 (95%CI = 1.23-7.94); p = 0.016]. In the non-maintenance cohort, such factors included ≥ 1 line of therapy [OR: 3.93 (95%CI = 1.00-15.38); p = 0.04] and a lower absolute neutrophil count at induction completion. Differences in the likelihood of DON development between patients receiving maintenance with obinutuzumab or rituximab possibly reflect mechanistic dissimilarities between type I and type II MoAbs. Regardless, prolonged MoAb use bears a mitigatory effect, reducing recurrence of DON. The findings obtained could assist in predicting the risk of DON in individual FL patients, optimizing informed treatment choices.

Keywords: Anti-CD20 monoclonal antibodies; Delayed-onset neutropenia; Follicular lymphoma; Maintenance therapy; Obinutuzumab.

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Conflict of interest statement

Declarations. Ethics Statement: All the procedures involved in this study were in accordance with the ethical standards of the. Institutional Review Board of the Rambam Health Care Campus (Approval # RMB-D-0227-21) and with the 1964 Helsinki Declaration and its later amendments. All the participants signed the Informed Consent Form. Conflict of interest: The authors declare no competing interests.

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