Improvement in the outcomes of mantle cell lymphoma in the last decade: a real-life non interventional study of the Croatian Cooperative Group for Hematologic Diseases.

AIM: To compare the outcomes of Croatian patients with mantle cell lymphoma (MCL) who started treatment in 2007 and 2008 (historical cohort) and of those who started treatment between 2015 and 2017 (recent cohort). METHODS: The historical cohort consisted of 40 patients who started treatment with rituximab in 2007 and 2008. Data on the recent cohort, consisting of 89 patients, were collected retrospectively from the electronic databases of Croatian hospitals with hematology units. Demographic characteristics and data on induction regimens, autologous stem cell transplantation (ASCT), and rituximab maintenance in the first remission, event-free survival (EFS), and overall survival (OS) were available for both cohorts, and data on cell morphology, mantle cell international prognostic index (MIPI), and Ki67 expression only for the recent cohort. RESULTS: The recent cohort had significantly better two-year EFS and OS (EFS 58% vs 40%, P=0.014; OS 80% vs 56%, P=0.009), especially in patients below 65. In univariate analysis, induction regimen, ASCT, and maintenance were significant prognostic factors for EFS and the former two for OS. In the multivariate analysis, only ASCT remained significant. Bendamustine+rituximab (BR) induction improved the outcomes of non-transplantable patients over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, steroid). Blastoid morphology and high MIPI were adverse prognostic factors for EFS and OS. CONCLUSION: In the last decade, the outcome of newly diagnosed MCL patients improved. ASCT in the first remission was the main contributor in transplantable patients and BR in non-transplantable. Regularly updated national guidelines may help in a timely adoption of new treatments, thus improving the results.

FDA's and EMA's approval of brentuximab vedotin for advanced Hodgkin lymphoma: Another player in the town?

ECHELON-1 study is a randomized open-labeled controlled trial investigating whether addition of brentuximab vedotin to chemotherapy offers benefit over the standard chemotherapy regimen in advanced Hodgkin lymphoma. After a median follow-up of 24.6 months, it has met its primary endpoint the reduction of modified progression-free survival being 23 percent. However, the beneficial effects have not been seen across all subgroups leading to further questions. The main aim of this review is to tackle these questions to provide the reader with in-depth insight of pros and cons of this novel, promising but ultimately controversial regimen.

BENDAMUSTINE: AN OLD DRUG IN THE NEW ERA FOR PATIENTS WITH NON-HODGKIN LYMPHOMAS AND CHRONIC LYMPHOCYTIC LEUKEMIA.

- The aim of this review is to present data on bendamustine, a non-cross resistant alkylating agent, alone or in combination for treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Bendamustine is currently approved for rituximab-resistant indolent NHL and CLL in patients not fit for conventional chemotherapy. Recent studies have shown superiority of bendamustine combination with rituximab (B-R) in first line treatment of indolent NHLs and mantle cell lymphoma, suggesting a shift of the standard of care in this setting. B-R regimen has also shown efficacy in relapsed setting suggesting the possible treatment option for patients failing conventional chemotherapy. In rituximab-resistant NHL, the recent GADOLIN study exploring the addition of obinutuzumab to bendamustine has yielded impressive result changing the standard of care in this hard-to-treat population. Concerning CLL, despite inferiority to the standard of care in young fit patients, as defined in CLL10 study, B-R has yielded a more beneficial toxicity profile and its use in first line treatment should be decided individually. In relapsed setting, the addition of ibrutinib to B-R has shown superior results compared to B-R alone, possibly changing the paradigm of treatment of relapsed CLL. In conclusion, bendamustine as a single agent or in combinations has shown activity with acceptable toxic profile in the treatment of patients with indolent NHLs or CLL without del(17p) mutation.

The fading star of obinutuzumab-chlorambucil regimen in patients with comorbidities with chronic lymphocytic leukemia - are we ready for chemo-free immunotherapy approach?

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries occurring typically in elderly patients. These patients often present with comorbidities limiting treatment options. During the last decade, the treatment paradigm has rapidly changed with the introduction of novel oral targeted agents and monoclonal antibodies. AREAS COVERED: The review focuses on the combination of type II antiCD20 antibody obinutuzumab in combination with chemotherapy or oral targeted agents in patients not suited for fludarabine-based therapy because of comorbidities or age. The main focus of the review is whether classical immunochemotherapy with obinutuzumab-chlorambucil is still a valid therapeutic option or whether the combination of obinutuzumab and ibrutinib or venetoclax presents novel standard of care. EXPERT OPINION: Both pivotal and registrational studies iLLLUMINATE study testing the combination of ibrutinib and obinutuzumab and CLL14 study testing the fixed combination of venetoclax and obinutuzumab have shown major benefit over chemoimmunotherapy approach in this population. Furthermore, they have excellent activity in high-risk subgroups of CLL paving the road toward a chemo-free immunotherapy approach in this setting. However, there are some pitfalls in these strategies warranting further research.