Report of consensus panel 1 from the 11th International Workshop on Waldenstrom's Macroglobulinemia on management of symptomatic, treatment-naïve patients.

Consensus Panel 1 (CP1) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with updating guidelines for the management of symptomatic, treatment-naïve patients with WM. The panel reiterated that watchful waiting remains the gold standard for asymptomatic patients without critically elevated IgM or compromised hematopoietic function. For first-line treatment, chemoimmunotherapy (CIT) regimens such as dexamethasone, cyclophosphamide, rituximab (DRC), or bendamustine, rituximab (Benda-R) continue to play a central role in managing WM, as they are effective, of fixed duration, generally well-tolerated, and affordable. Covalent BTK inhibitors (cBTKi) offer a continuous, generally well-tolerated alternative for the primary treatment of WM patients, particularly those unsuitable for CIT. In a Phase III randomized trial updated at IWWM-11, the second-generation cBTKi, zanubrutinib, was less toxic than ibrutinib and induced deeper remissions, thus categorizing zanubrutinib as a suitable treatment option in WM. While the overall findings of a prospective, randomized trial updated at IWWM-11 did not show superiority of fixed duration rituximab maintenance over observation following attainment of a major response to Benda-R induction, a subset analysis showed benefit in patients >65 years and those with a high IPPSWM score. Whenever possible, the mutational status of MYD88 and CXCR4 should be determined before treatment initiation, as alterations in these 2 genes predict sensitivity towards cBTKi activity. Treatment approaches for WM-associated cryoglobulins, cold agglutinins, AL amyloidosis, Bing-Neel syndrome (BNS), peripheral neuropathy, and hyperviscosity syndrome follow the common principle of reducing tumor and abnormal protein burden rapidly and deeply to improve symptoms. In BNS, ibrutinib can be highly active and produce durable responses. In contrast, cBTKi are not recommended for treating AL amyloidosis. The panel emphasized that continuous improvement of treatment options for symptomatic, treatment-naïve WM patients critically depends on the participation of patients in clinical trials, whenever possible.

Novel Treatment Strategies in the Management of Waldenström Macroglobulinemia.

PURPOSE OF REVIEW: Recent advances the genomic profiling of patients with Waldenström macroglobulinemia (WM) have led to the identification of novel therapeutic targets in these patients. In this review, we cover the current standard of care and the recently evaluated novel approaches with high potential to be incorporated in the therapeutic armamentarium against WM. RECENT FINDINGS: The MYD88L265P mutation is the most common genomic abnormality in WM, and is encountered in 80-95% of patients, making it an important target for drug development. The success of the first-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has generated tremendous interest in the study of more selective and potent BTK inhibitors. Additionally, the identification of CXCR4WHIM mutations in up to approximately 40% of patients with WM has fueled research regarding their implication on systemic therapy in WM. In a rapidly advancing field of targeted therapies, the treatment options for patients with WM are expanding as researchers continue to uncover and harness the survival pathways active in this hematologic malignancy.

Challenges and Strategies in the Management of Multiple Myeloma in the Elderly Population.

PURPOSE OF REVIEW: Approximately one half of the patient-population in multiple myeloma (MM) is > 70 years at diagnosis. Despite notable strides in the management and improved survival, MM remains incurable, with an increasing proportion of elderly patients comprising the relapsed-refractory cohort. RECENT FINDINGS: The arbitrary age cutoff at 65 years to define the elderly patient-population has evolved to a more nuanced categorization, incorporating a comprehensive assessment for determining frailty prior to commencing treatment. This step is critical in determining the therapy-intensity, including transplant-eligibility, to minimize toxicity. Dose-modifications are crucial, as the merits of continuous therapy are becoming evident in this patient-population. Bortezomib, lenalidomide, and dexamethasone (VRd) combination has emerged as standard of care for newly diagnosed MM. Fixed-duration Rd followed by reduced-dosed continuous R may be considered in select frail patients with standard-risk MM. Herein, we review the unique challenges encountered in elderly MM and discuss strategies for optimal management.

Ixazomib: a novel drug for multiple myeloma.

INTRODUCTION: Proteasome inhibitors (PIs) have been an integral part of treatment for multiple myeloma (MM) over the past decade. Many newer PIs are being evaluated in pre-clinical and clinical setting, with an aim to improve the safety, efficacy and resistance profile of this class of drugs. Ixazomib is the first oral PI with a robust efficacy and favorable safety profile in MM. Areas covered: This review provides an overview of the (i) pharmacology and dosing of ixazomib, (ii) the efficacy and safety data from clinical studies, (iii) highlight the various novel combinations that have been reported, and (iv) give an overview of the ongoing studies with ixazomib. The review aims to provide a broad overview of the drug and compare and contrast it with the currently available alternatives. Expert commentary: The oral formulation of ixazomib makes it unique in the sense that it is an integral part of the only currently approved oral triplet for relapsed/refractory MM that incorporates both a PI and an immunomodulatory agent. The clinical efficacy, ease of administration, tolerability and synergy with other drug classes make ixazomib a valuable arsenal in the increasingly widening therapeutic armamentarium against MM.

The Effect of Implementing Gene Expression Classifier on Outcomes of Thyroid Nodules with Indeterminate Cytology.

Thyroid nodules are classified into six cytological categories under the Bethesda classification system. Two of these categories, atypical of undetermined significance (AUS) and suspicious for a follicular neoplasm (SFN), are further labeled as "indeterminate" diagnosis. Starting in June, 2012, Kansas University-Wichita Endocrine clinic implemented Afirma® Gene Expression Classifier (AGEC) to evaluate the need for surgical resection of thyroid nodules in patients with an indeterminate diagnosis. Electronic medical records of patients who underwent thyroid nodule fine-needle aspiration from 2004-2014 were reviewed. The aim of this study was to find whether implementing AGEC was associated with decreased surgical recommendation rate, decreased cost, and increased incidence of thyroid malignancy diagnosed by surgery in patients with indeterminate diagnosis. A total of 299 consecutive patients' charts were screened. Sixty-one (20 %) patients had an indeterminate diagnosis. Out of these, 27 (44 %) patients underwent evaluation before and 34 (56 %) patients underwent evaluation after AGEC implementation, respectively. Surgical recommendation for patients with indeterminate finding decreased from 81.5 to 50 % (p = 0.01) after AGEC implementation. Surgical pathology was read as malignant in 20 and 85.7 % (p < 0.01) of patients before and after AGEC implementation, respectively. Primary cost-benefit estimate showed implementing AGEC has saved $1048/patient in medical evaluation and initial management of patients with indeterminate diagnosis. AGEC implementation has decreased the number of surgical recommendations, has lowered financial burden, and has increased incidence of thyroid malignancy diagnosed by surgical pathology in patients with indeterminate diagnosis of thyroid nodules.