This review discusses the role of the BRAF/mitogen activated protein kinase pathway in modulating antitumor immunity and how this provides a rationale for combining BRAF- targeted therapy with immunotherapy to enhance therapeutic responses. Summary points Studies have clearly demonstrated that inhibition of the BRAF/mitogen activated protein kinase (MAPK) pathway has a profound effect on antitumor immunity and the tumor microenvironment as a whole through a number of different mechanisms, including effects on dendritic cell function and natural killer cell activation. In addition to the favorable immune effects of BRAF/MAPK pathway blockade, immune mechanisms of therapeutic resistance to these agents also exist—including through the induced expression of immunomodulatory molecules within the tumor microenvironment, and through stromal-mediated immunosuppression. This provides a sound rationale for developing combination strategies with targeted therapy and immunotherapy, though problems exist regarding optimal combination regimens and associated toxicity, and the optimal timing and sequence of therapy. Ongoing trials highlight these difficulties; insights have been gained through longitudinal tissue- and blood-based analyses in patients during treatment with these agents as monotherapy, indicating that translational studies should be built into trials to better inform mechanisms of response and resistance to these regimens and to gain insight into potential mechanisms of toxicity. Treatment regimens need to be carefully studied in preclinical models if we are to understand the mechanisms behind potential treatment combinations. A personalized approach is required if optimal combination strategies are to be designed that improve therapeutic responses whilst reducing resistance to therapy. Reddy SM, Reuben A, & Wargo JA. Curr Oncol Rep 2016; 18: 42. doi:10.1007/s11912-016-0531-z

This review discusses current multiple myeloma treatment options, effective symptom management approaches, and practical strategies for supportive care. Summary points Recent therapeutic advances have significantly improved overall survival in patients with multiple myeloma (MM), with a concomitant increase in susceptibility to disease- and treatment-related symptoms. Current therapeutic regimens for relapsed/refractory MM include proteasome inhibitors (eg, bortezomib, carfilzomib) and immunomodulatory agents (eg, thalidomide, lenalidomide, pomalidomide), alone or in combination with chemotherapy or corticosteroids. Toxicities associated with agents and combination regimens used in the treatment of MM include myelosuppression, venous thromboembolism, peripheral neuropathy, infections, fatigue, gastrointestinal disorders, and/or cardiac events. Treatment-specific tools and clinical assessments can be useful for optimizing dosing and schedule adjustments to increase therapy duration, and implementing supportive care strategies (such as growth factors, transfusional support, intravenous hydration, bisphosphonates, and antiviral therapies) to manage treatment-related symptoms. Effective management of the patient with MM requires knowledge of the disease and of treatment-associated adverse events in addition to preventative measures, supportive care strategies, and management of comorbidities. Patient education and individualized survivorship plans can play a role in achieving maximal patient responses to treatment. Improved survival after MM diagnosis has led to increased patient susceptibility to other diseases and comorbidities due to advanced age, thus optimal symptom management will be important to maximize quality of life for patients in addition to disease control and survival. Colson K. Support Care Cancer 2015; 23: 1431–1445. doi:10.1007/s00520-014-2552-1

Immunomodulatory agents Lenalidomide This is a second generation thalidomide analog and immunomodulatory agent that has shown encouraging results in CLL/SLL patients with del17p [52].

More recently, the landscape of MM therapy continues to expand further with the approval of next generation proteasome inhibitors and immunomodulatory agents as well as the recent approval of new drugs with novel mechanisms of action including monoclonal antibodies and histone deacetylase inhibitors. 15, 16, 17  With the rapid changes in MM therapy, our goal with this review is to analyze the current literature and provide recommendations for maintenance therapy in MM, primarily with lenalidomide and bortezomib.

In a phase I 3 + 3 dose escalation study, chloroquine added to gemcitabine is shown to be well tolerated in patients with metastatic or unresectable pancreatic cancer, with promising effects on the clinical response to the chemotherapy. Samaras P et al. Cancer Chemother Pharmacol 2017. doi:10.1007/s00280-017-3446-y

In this review, Younes et al describe the most promising agents in clinical development for the treatment of lymphoma and provide expert opinion on new strategies that may streamline drug development. Nat Rev Clin Oncol  2017; 14: 335–346. doi:10.1038/nrclinonc.2016.205

MOA of agents approved or under development for MM.

The immunomodulatory subtype is characterized by immune cell processes and immune signaling cascades.

Like combination checkpoint blockade strategies, much enthusiasm exists for combined treatment strategies with other immunomodulatory agents 115, 116 .