Drug-induced pneumonitis risk in diffuse large B-cell/follicular lymphoma patients treated with R-CHOP-like regimen is associated with the use of granulocyte colony-stimulating growth factors.

BACKGROUND: Rituximab-based combinations are the standard of care in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug-induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony-stimulating factors (G-CSF) are supportive agents commonly used to prevent neutropenic infections. G-CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. METHODS: In this retrospective study, we reported the G-CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R-CHOP-type immunochemotherapy. RESULTS: In 72% of patients, the treatment included a G-CSF support. The overall incidence of treatment-induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G-CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3-4) also increased the risk of DIP. CONCLUSIONS: These findings suggest that the use of G-CSF increases the risk of DIP, when used in combination with rituximab-containing regimen.

Interim and end-of-treatment PET-CT suffers from high false-positive rates in DLBCL: Biopsy is needed prior to treatment decisions.

The application of positron emission tomography (PET)-computed tomography (CT) in treatment response evaluation has increased in diffuse large B-cell lymphoma (DLBCL), although its predictive value is controversial. We retrospectively analyzed the rate of false-positive PET-CTs performed as interim (n = 94) and end-of-treatment (n = 8) assessments among 102 DLBCL patients treated during 2010-2017 at Oulu University Hospital. In PET-CT Deauville score ≥4 was regarded as positive. A biopsy was performed on 35 patients, and vital lymphoma tissue was detected from nine patients. Positive biopsy findings were associated with poor disease outcomes in this study. This difference was statistically significant: 2-year failure-free survival (FFS) was 44% in patients with a positive biopsy versus 83% for those with a negative biopsy (p = 0.003). The corresponding overall survival (OS) rates were 53% versus 95% (p = 0.010). In the multivariate analyses, a negative biopsy was an independent protective factor in FFS (Hazard Ratio (HR) 0.093 (95% confidence interval [CI] 0.017-0.511); p = 0.006) unrelated to the International Prognostic Index (IPI) (HR 1.139 [95% CI 0.237-5.474] p = 0.871) or stage (HR 1.365 [95% CI 0.138-13.470]; p = 0.790). There was no statistically significant difference in OS according to the PET results, but the FFS rate was significantly higher in patients with a negative PET. The value of PET-CT as an evaluation method suffers from a high false-positive rate, and it is inadequate alone for the justification of treatment decisions. Biopsy results provide more reliable prognostic information for the evaluation of treatment response and outcome and should be used to assess patients with positive PET-CT scans.

Significance of bulky mass and residual tumor-Treated with or without consolidative radiotherapy-To the risk of relapse in DLBCL patients.

Bulky and residual tumor are considered to increase the risk of relapse in diffuse large B-cell lymphoma (DLBCL) patients. Radiotherapy is conventionally used to reduce the risk, but the evidence is controversial. We performed a retrospective analysis to evaluate the significance of bulky and residual tumor treated with or without radiotherapy in DLBCL patients. We analyzed 312 DLBCL patients treated from 2010-2017 in Oulu University Hospital. A bulky tumor was detected in 123 patients and 55 of these patients (44.3%) received consolidative radiation therapy (RT) to the bulky tumor. Residual tumor meeting the required criteria was found in 138 (39.3%) patients, and 65 (45.5%) of these patients received consolidative RT to the site of residual tumor. iPET-CT scans were performed in 102 patients. In multivariate analyses, bulky was an independent risk factor in limited stage patients in progression free survival (HR 6.43 [95%CI 1.609-25.710]; P = .008) not related to International prognostic index (HR 1.35 [95% CI 0.256-7.124]; P = .724) or age (HR 1.62 [95% CI 0.468-5.638]; P = .445). This was not seen in advanced stage patients or in patients with residual tumor. Radiotherapy to the bulky or residual tumor was not able to improve the long-term PFS of patients. In this study, it appears that performing iPET is the most convincing method in improving evaluation and in finding patients with increased risk of relapse. Evidently, patients with negative iPET will not benefit from including RT in the treatment after metabolic complete response (CR), and patients with primary refractory disease are most likely in the group of positive iPET.

Promising treatment results with blood brain barrier disruption (BBBD) based immunochemotherapy combined with autologous stem cell transplantation (ASCT) in patients with primary central nervous system lymphoma (PCNSL).

Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation. We analysed 25 patients (age range: 40-71 years) who were treated in first or second line with BBBD therapy. When we started BBBD treatment, patients had relapsed or refractory PCNSL or they did not tolerate Bonn-like therapy. In recent years, some of the patients were treated in first line. We found promising response rates. Altogether 19 (76 %) of the patients achieved a complete response (CR). Two-year progression-free survival (PFS) and overall survival (OS) rates were 61 and 57 % respectively and the five-year OS was 47 %. Patients who were treated with a five-drug therapy had a very promising prognosis. The CR rate was 100 % in first-line therapy and 60 % in relapsed cases. These findings suggest that BBBD is a promising therapy for PCNSL, especially for patients in first line, but also for patients with relapsed or refractory disease after conventional chemotherapy, who commonly have a very poor prognosis. Treatment-related toxicity was generally manageable. Thus, BBBD followed by ASCT could be a treatment of choice in transplant-eligible patients with PCNSL.