Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non-Hodgkin lymphomas: A retrospective cohort study

• SH after chemo-immunotherapy is a risk factor for iNHL patients.
• Our study investigated incidence and risk factors for SH, infective complications.
• Incidence of SH was 2.2 × 1000 person-years.
• Exposure to Fbs ± R and ASCT was statistically associated with SH incidence.
• Exposure to CHOP ± R or CVP ± R was not a risk factor as well as Rituximab exposure.

The occurrence of secondary hypogammaglobulinemia (SH) after chemo-immunotherapy represents a potential side effect in patients with indolent non-Hodgkin lymphomas (iNHL). Few data are available on SH occurring after chemotherapy and/or Rituximab (R). We retrospectively investigated the incidence and the risk factors for SH and infectious complications in patients with iNHL after chemo-immunotherapy. Two hundred and sixty six patients treated between 1993 and 2011 were studied. Patients with a basal hypogammaglobulinemia or a monoclonal component were excluded. The incidence of SH was 2.2 × 1000 person-years (95% CI 1.6–2.9). Exposure to Fludarabine-based schedules (Fbs) ± R was associated with a hazard ratio (HR) of 18.1 (95% CI: 4.3–77.0). Conversely, exposure to CHOP ± R or CVP ± R was not a risk factor (HR 0.3, 95% CI: 0.1–0.8; HR 0.3, 95% CI: 0.08–1.4, respectively). The role of R was studied comparing cohorts differing only for R; no differences were found comparing R-CHOP/R-CVP versus CHOP/CVP (HR 1.07, 95% CI: 0.38–3.05) and R–Fbs versus Fbs (HR 2.07, 95% CI: 0.62–6.99). Autologous stem cell transplantation (ASCT) is also a risk factor (HR: 5.2, 95% CI 2.1–13.0). SH patients presented a high risk for pneumonia development (HR 7.07 95% CI: 2.68–18.44). We recommend monitoring of serum immunoglobulins in an attempt to reduce the probability of infection after Fbs or ASCT.