Management of Relapsed/Refractory Multiple Myeloma with Bendamustine-Bortezomib-Dexamethasone

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. It accounts for approximately 1.8% of all hematologic and solid cancers and slightly > 15% of hematologic malignancies in the United States. MM is most frequently diagnosed among people aged 65 to 74 years (median age 69 years). During 2016, the American Cancer Society estimated that 30.330 new cancer cases occurred in USA, with 12.650 deaths. Over the past decade, statistical analysis show that the rates for new MM cases have been increasing an average of 0.8% each year. However, these analysis also reveal that death rates have been declining an average of 0.8% each year (period 2004-2013) thanks to the availability of newer and more effective treatment options. MM is typically sensitive to different classes of cytotoxic drugs, both as frontline treatment and as treatment for relapsed disease. Unfortunately, even if responses are typically durable, nowadays MM is not considered curable with current approaches. However, treatment of MM has been rapidly evolving, due to the introduction of new classes of drugs, such as proteasome inhibitors, immunomodulatory drugs (IMIDs), histone deacetylase inhibitors and monoclonal antibodies and new indications for old classes of drugs, such as alkylating agents. Moreover, there is increasing understanding of MM tumor biology, creating the rational for new combinations of drugs and new therapies development. Discover of the associated cytogenetic abnormalities confirm the hypothesis that MM is a heterogeneous disease, suggesting that risk-adapted therapies and individualizing treatment will further help to improve patient management. Bendamustine is a molecule largely adopted in the past as effective chemotherapeutic agent in several types of hematological and non-hematological malignancies. Its unique mechanism of action, both as alkylating agent and antimetabolite, probably accounts for its wide efficacy profile also in the treatment of relapsing/refractory multiple myeloma. In this specific clinical setting, in which patients experience several therapy lines and have poor prognosis, bendamustine combined with bortezomib and dexamethasone, is emerging as an effective salvage therapy, also in the era of new drugs. In fact, despite the introduction of so-called novel agents, such as second generation proteasome inhibitors (carfilzomib) or third generation immunomodulatory drugs (pomalidomide), many trials have demonstrated that bendamustine in combination with other agents is also a valid therapeutic option as these mentioned above. This retrospective, observational study aimed to evaluate, in a real-life setting, a cohort of heavily pre-treated patients affected by relapsing/refractory multiple myeloma, whose salvage therapy consisted in courses of bendamustine-bortezomib-dexamethasone. Efficacy and safety data were evaluated, focusing especially on effectiveness of this regimen on previously bortezomib-refractory patients and on its tolerability. Data on efficacy and safety of our real-life experience were highly comparable to those of major trials adopting the same regimen in the same clinical setting, demonstrating how it is a feasible salvage therapeutic option, in a context of poor treatment choices. Moreover, our data revealed how bendamustine addition could overcome a previous pharmacological refractoriness to bortezomib, leading to clinical response also those patients already treated with this proteasome inhibitor

An overview of prognostic markers in patients with CLL

Chronic lymphocytic leukemia (CLL) is a low-grade B-cell lymphoproliferative disorder. It is the most prevalent type of leukemia in the western countries, with a median age at diagnosis of 70 years. In 2023, it is estimated that there will be 18,740 new cases of CLL, and an estimated 4,490 people will die of this disease. It represents 1.0% of all new cancer cases in the U.S. The rate of new cases was 4.6 per 100,000 men and women per year based on 2016–2020 cases, age-adjusted. Death rates from CLL are higher among older adults, or those 75 and older. The death rate was 1.1 per 100,000 men and women per year based on 2016–2020 deaths, age-adjusted. A common question that patients with CLL ask during their first clinic visit is: “How long will it be before I would need treatment?” Although this might seem like a simple question, the answer is not straight forward. CLL is a heterogenous disease, with a variable clinical course. Some patients may present with an aggressive disease requiring early initiation of treatment, while others have an indolent course and some, having so called smoldering CLL, may never need treatment. The variability in disease course can make predicting disease prognosis a complicated process. This brings forth the importance of establishing prognostic models that can predict disease course, time to treatment, and survival outcomes in such a heterogenous disease. The Rai and Binet staging systems were developed in the late 1970s to early 1980s. They separated patients into different stages based on clinical characteristics and laboratory findings. These simple staging systems are still in use; however, several prognostic markers need to be added for an individualized assessment and, with the recent development of genomic techniques leading to better understanding of CLL at the molecular level, newer prognostic markers have emerged

Reply to the letter to the editor “chronic disseminated candidiasis” by Kenneth Rolston

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Safety and comfort of domestic bortezomib injection in real-life experience

Despite novel agents, multiple myeloma is still an incurable disease, especially for elderly and frail patients, who are difficult to manage for concomitant comorbidities as the therapeutic options are limited and the response to chemotherapy is often short. We report our evaluations upon safety and efficacy of domestic subcutaneous bortezomib in elderly and frail patients candidate to bortezomib-melphalan-prednisone (VMP) regimen. We confirmed that overall incidence of adverse events, including peripheral neuropathy, was low, and in no case required admission to emergency service, contributing to reduce the rate of therapy discontinuation. These results confirm the effectiveness and safety of subcutaneous bortezomib, in a real-life-experience, and define a new possibility of safe auto-administration in a comfortable domestic setting. We suggest that domestic treatment can significantly improve the quality of life of the patients, avoiding unnecessary transfer to the hospital without reducing treatment efficacy

Pegfilgrastim in primary prophylaxis of febrile neutropenia following frontline bendamustine plus rituximab treatment in patients with indolent non-Hodgkin lymphoma: a single center, real-life experience

In this prospective study, the impact of granulocyte colony-stimulating factors (G-2 CSF) administered during induction treatment with bendamustine plus rituximab for indolent non- Hodgkin Llymphoma (NHL) was evaluated by comparing patients who received secondary prophylaxis with filgrastim (control group) versus. patients who received pegfilgrastim as primary prophylaxis (peg-group). The primary endpoint was the incidence rate of febrile neutropenia (FN)- related chemotherapy disruptions (regarding dose-dense and/or dose-intensity of schedule). The Ssecondary endpoint included days of hospitalization due to FN, and G-CSF-related side effects (grade ≥3 WHO toxicity criteria) in each group

A Frontline Approach With Peripherally Inserted Versus Centrally Inserted Central Venous Catheters for Remission Induction Chemotherapy Phase of Acute Myeloid Leukemia: A Randomized Comparison

BACKGROUND: The incidence of peripherally inserted central catheter (PICC)-related adverse events has been uncertain in the setting of acute myeloid leukemia (AML) compared with the incidence of centrally inserted central catheter (CICC) adverse events. PATIENTS AND METHODS: We conducted a monocentric, randomized trial of patients with previously untreated AML. Of the 93 patients, 46 had received a PICC and 47 had received a CICC as frontline intravascular device. Thereafter, all patients underwent intensive chemotherapy for hematologic remission induction. The primary endpoint was catheter-related (CR)-bloodstream infection (BSI) and venous thrombosis (VT) rate. The secondary endpoints catheter malfunction, catheter removal, and patient overall survival. RESULTS: The CR-BSI and CR-VT rate in the PICC and CICC groups was 13% and 49%, respectively, with a difference of 36 percentage points (relative risk for CR-BSI or CR-VT, 0.266; P = .0003). The CR-BSI incidence was 1.4 and 7.8 per 1000 catheters daily in the PICC and CICC groups, respectively. Among the CR thromboses, the symptomatic VT rate was 2.1% in the PICC group and 10.6% in the CICC group. In the CICC group, 16 of the 47 patients (34%) had the catheter removed for BSI (n = 5), septic thrombophlebitis (n = 4), VT (n = 2), or malfunction (n = 5) a median of 7 days after insertion. In the PICC group, only 6 of the 46 patients (13%) required catheter removal for VT (n = 2) or malfunction (n = 4). At a median follow-up of 30 days, 6 patients in the CICC group died of CR complications versus none of the patients in the PICC group (P = .012). Using PICCs, the reduction in BSI and symptomatic VT decreased mortality from CR infection and venous thromboembolism. In contrast, the CICC approach led to early catheter removal mostly for difficult-to-treat infectious pathogens. CONCLUSION: Our data have confirmed that BSI and symptomatic VT are the major complications affecting frontline central intravascular device-related morbidity in the leukemia setting. The use of a PICC is safer than that of a CICC and maintains the effectiveness for patients with AML undergoing chemotherapy, with an approximate fourfold lower combined risk of infection or thrombosis at 30 days