Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol). MATERIALS AND METHODS: This retrospective multicenter study was conducted between 2000 and 2020 at all nine breast centers across Tyrol, Austria. Using the cancer registry, the total Tyrolean population was screened for all patients with breast cancer. All patients with breast cancer and bone metastases receiving antiresorptive therapy were finally included in the study. RESULTS: From 8,860 patients initially screened, 639 individuals were eligible and included in our study. Patients received antiresorptive therapy once per month without de-escalation of therapy. MRONJ was diagnosed in 56 (8.8%, 95% CI, 6.6 to 11.0) patients. The incidence of MRONJ was 11.6% (95% CI, 8.0 to 15.3) in individuals treated with denosumab only, 2.8% (95% CI, 0.7 to 4.8) in those treated with bisphosphonates only, and 16.3% (95% CI, 8.8 to 23.9) in the group receiving bisphosphonates followed by denosumab. Individuals developed MRONJ significantly earlier when treated with denosumab. Time to MRONJ after treatment initiation was 4.6 years for individuals treated with denosumab only, 5.1 years for individuals treated with bisphosphonates only, and 8.4 years for individuals treated with both consecutively. CONCLUSION: MRONJ incidence in breast cancer patients with bone metastases was found to be considerably higher, especially for patients receiving denosumab, when compared with available data in the literature. Additionally, patients treated with denosumab developed MRONJ significantly earlier.

A success story: how a single targeted-therapy molecule impacted on treatment and outcome of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a rather aggressive disease and the natural course of this lymphoma is very dismal. However, first the introduction of anthracycline-containing chemotherapy regimens and then the addition of rituximab were important steps forward. Since no complete real-life analyses have yet been published, we analyzed all patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in the whole region of Tyrol and compared the results to a historical CHOP(-like)-treated cohort. Two hundred and nineteen consecutive patients underwent R-CHOP and 72% achieved a complete remission (CR); 20% suffered a relapse and 31% died. 5-Year progression-free survival (PFS) and overall survival (OS) were 56% and 69%, respectively. We identified several parameters influencing PFS and OS significantly in univariate analysis, but only stage III/IV and hemoglobin <13 g/dl were independent prognosticators for PFS and age >60 years for OS. In comparison to the CHOP(-like)-treated group, the CR rate was similar, while the percentage of relapse was nearly twice in the historical cohort, namely 44%. This translated into a dramatically improved PFS and OS for the R-CHOP group. In conclusion, in a real-life setting R-CHOP results in high percentages of response and long-term remission. Moreover we showed that in the rituximab era, factors other than the single parameters of the international prognostic index significantly influence PFS and OS. Finally, we confirm the independent impact of rituximab on the outcome of an unselected population with DLBCL.

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals.

BACKGROUND: The objective was to demonstrate feasibility and therapeutic efficacy of routine clinical use of the bendamustine/rituximab combination in lymphoproliferative diseases. PATIENTS AND METHODS: Data were collected retrospectively from 71 patients treated with bendamustine/rituximab combination in Tyrol/Austria. Toxicities, therapeutic response, and survival outcome in the various lymphoma entities were analyzed. RESULTS: There was considerable hematotoxicity, with neutropenia and thrombocytopenia of grade 3 or 4 in 33% and 18%, respectively. Interestingly, severe infection of grade 3 or 4 was observed in a remarkable percentage of patients with aggressive lymphoma and CLL (21% and 28%, respectively) but not in indolent lymphoma (p = 0.027). Overall, the therapeutic efficacy of bendamustine/rituximab was encouraging. In CLL, an overall response rate (ORR) of 65% was achieved. Notably, in the seven previously untreated CLL patients, ORR was 86%. The therapy was effective across all FISH-cytogenetic subgroups, except for the five patients harboring 17p deletion with unfavorable prognosis (PFS 2.7 months, OS 9.3 months). In indolent lymphoma (n = 25), the bendamustine-rituximab combination induced a remarkable therapeutic effect (ORR 96%, median PFS and OS not reached). In aggressive lymphoma (n = 20), ORR was 50%; in International Prognostic Index high-risk patients (4 or 5 risk factors, n = 10), ORR was only 20%, significantly inferior than in low/intermediate risk patients (ORR 70%; p = 0.025). CONCLUSIONS: In the routine setting aside clinical studies, bendamustine/rituximab therapy resulted in marked clinical responses, especially in CLL and indolent lymphoma. In aggressive lymphoma, the combination of bendamustine and rituximab was effective in favorable risk patients.