Advancements in the Management of Follicular Lymphoma: A Comprehensive Review

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma in Western countries. While FL is generally incurable, standard initial therapies are associated with high response rates and durable remissions for most patients. In addition, novel targeted agents and immunotherapies are changing the treatment algorithm for patients with relapsed or refractory disease. This review discusses the initial staging, prognosis, and treatment options for newly diagnosed and relapsed/refractory FL. Initial treatment options for FL include active surveillance, radiotherapy, rituximab monotherapy, and chemoimmunotherapy. Staging with positron emission tomography/computed tomography and bone marrow biopsy is crucial for identifying early-stage patients. Most patients with FL will receive chemoimmunotherapy as the initial treatment with options including rituximab or obinutuzumab plus cyclophosphamide, vincristine, and prednisone; cyclophosphamide, doxorubicin, vincristine, and prednisone; bendamustine; or lenalidomide. No significant differences in overall survival have been observed in randomized studies comparing these regimens. Maintenance therapy with rituximab or obinutuzumab in responders to initial chemoimmunotherapy improves progression-free survival. For relapsed/refractory FL, treatment options include chemoimmunotherapy, lenalidomide-based regimens, tazemetostat, chimeric antigen receptor (CAR)-T cell therapy (axicabtagene ciloleucel and tisagenlecleucel), and CD3/CD20 bispecific antibodies (BsAbs). Given the encouraging outcomes obtained with CAR-T cell therapy and BsAbs, multiple trials are testing these highly active agents in earlier lines of therapy and among high-risk patients with early relapse after frontline chemoimmunotherapy. Additional studies and follow-up are needed to understand how these novel agents may further change treatment algorithms for FL.

Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.

Do Alarmins Have a Role in Multiple Myeloma?

Objective: Calprotectin (CLP), S100A6, and high mobility group nucleosome-binding protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to investigate the relationships of serum CLP, S100A6, and HMGN1 levels with the clinical and laboratory findings of patients with multiple myeloma (MM) and their roles in the pathogenesis of MM. Materials and Methods: We measured the serum CLP, S100A6, and HMGN1 levels of 55 newly diagnosed patients and 32 healthy controls using the sandwich enzyme-linked immunosorbent assay method. The medical records of the patients were also reviewed. Results: Serum CLP, S100A6, and HMGN1 levels were significantly decreased in MM patients compared to the control group (p=0.012, p=0.001, and p=0.030, respectively). Receiver operating characteristic analysis was used to determine diagnostic cut-off values for serum CLP, S100A6, and HMGN1 of <98 ng/mL (area under the curve [AUC]: 0.663, 95% confidence interval [CI]: 0.554-0.761, p=0.009), <1174.5 pg/mL (AUC: 0.706, 95% CI: 0.598-0.799, p=0.001), and <440.18 pg/mL (AUC: 0.640, 95% CI: 0.530-0.740, p=0.03), respectively. CLP levels were found to be statistically significantly higher in patients with light chain MM (91.58±22.57 ng/mL) compared to heavy chain MM (79.42±15.83 ng/mL) (p=0.03). A negative correlation was observed between CLP and M protein, immunoglobulin G, globulin, and beta-2 microglobulin (correlation coefficients: -0.361, -0.370, -0.279, -0.300, respectively; p=0.024, p=0.06, p=0.04, p=0.0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in patients with newly diagnosed MM compared to the control group. These results suggest that CLP may bind to the paraprotein produced by heavy chain MM in the blood, causing its blood levels to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in cases of MM.