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Shaji K. Kumar

Multiple myeloma (MM) is a complex disease characterized by considerable genetic heterogeneity. The updated NCCN Guidelines for MM have added new “preferred” regimens for transplant and nontransplant candidates, and have moved some formerly “preferred” regimens to the “other” category. Supportive care has improved outcomes for patients, and new treatments in combination have extended survival for patients with MM. Novel agents on the horizon are poised to raise the bar even further.

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Shaji K. Kumar

The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as “preferred,” “other,” and “useful in certain circumstances.” For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy. Double (tandem) ASCT may benefit patients with high-risk cytogenetics, such as 17p deletion. Lenalidomide maintenance is the standard posttransplant approach and results in improved progression-free and overall survivals. For relapsed disease, a host of new agents have been shown to improve outcomes, mostly in combination with bortezomib or lenalidomide, but their selection depends largely on response and tolerability to prior therapies.

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Presenter: Shaji K. Kumar

For patients with newly diagnosed multiple myeloma (MM), treatment with 4-drug regimens produce deep responses and should be considered for those with high-risk features. Daratumumab + lenalidomide and dexamethasone is standard treatment for newly diagnosed patients not eligible for autologous stem cell transplantation (ASCT). Although lenalidomide remains standard maintenance therapy, in some instances more intensive regimens can be considered. ASCT is more effective when given up-front rather than delayed, but delaying transplantation until disease progression is acceptable. CAR T-cell therapy can provide durable responses, and 2 agents are now FDA-approved for use in multiple myeloma. Bispecific T-cell engagers are also effective for relapsed myeloma, as is the BCL2 inhibitor venetoclax, especially for patients with t(11;14) disease. An emerging novel class of drugs, the CELMoDs (cereblon E3 ligase modulator), target cereblon.

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Presenter: Shaji K. Kumar

The treatment of multiple myeloma (MM) has evolved over the past decade, yet it remains a chronic disease. Several trials of 4-drug induction regimens have resulted in deepening of disease response. With the emergence of multidrug regimens, questions have arisen regarding the role of autologous stem cell transplant (ASCT) in MM therapy and available treatment options after ASCT. Clinicians have also continued to improve the efficacy of maintenance therapies. In transplant-ineligible patients, the phases of treatment are less distinct; however, several regimens have demonstrated efficacy in this clinical setting. Future research should focus on individualizing treatment approaches.

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Presenter: Shaji K. Kumar

The treatment of multiple myeloma is marked by many recent advances, but for newly diagnosed patients the standard of care for induction remains the combination of a proteasome inhibitor, immunomodulatory drug, and dexamethasone. The role of a 4-drug induction regimen is still being defined, but can be considered for patients with high-risk disease. For patients who are eligible to undergo stem cell transplant, this approach remains the preferred option, but transplant can be delayed until relapse if patients prefer. In those who are not eligible for transplant, based on impressive data with daratumumab/lenalidomide/dexamethasone, this triplet should be considered as initial therapy. In patients with relapsed disease, it is important to switch treatment to new drug classes; for this, multiple combinations can be recommended. Updated guidelines now include new drugs for refractory disease: selinexor and belantamab mafodotin, both listed as “other regimens” in the NCCN Guidelines, can be considered.

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Presenter: Shaji K. Kumar

Although recent advances in the treatment of multiple myeloma have improved survival, it remains a chronic disease that requires a long-term treatment strategy. The key to achieving the best outcomes for patients is delivering the best “package” of treatment at a given stage. This means using optimal combinations that maximize benefit based on what patients have received previously and minimize treatment-related toxicity. Sequencing of regimens also plays an important role. As new agents and new classes of drugs continue to be approved for multiple myeloma, future strategies will use more individualized approaches to treatment.

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Muhamed Baljevic, Douglas W. Sborov, Ming Y. Lim, Jens Hillengass, Thomas Martin, Jorge J. Castillo, Michael B. Streiff, Shaji K. Kumar, and Natalie S. Callander

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.

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Shaji K. Kumar, Natalie S. Callander, Melissa Alsina, Djordje Atanackovic, J. Sybil Biermann, Jason C. Chandler, Caitlin Costello, Matthew Faiman, Henry C. Fung, Cristina Gasparetto, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Adetola Kassim, Michaela Liedtke, Thomas Martin, James Omel, Noopur Raje, Frederic J. Reu, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Steven P. Treon, Donna Weber, Joachim Yahalom, Dorothy A. Shead, and Rashmi Kumar

Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia. The recommendations specific to the diagnosis and treatment of patients with newly diagnosed MM are discussed in this article.

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Kenneth C. Anderson, Melissa Alsina, Djordje Atanackovic, J. Sybil Biermann, Jason C. Chandler, Caitlin Costello, Benjamin Djulbegovic, Henry C. Fung, Cristina Gasparetto, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Adetola Kassim, Amrita Y. Krishnan, Shaji K. Kumar, Michaela Liedtke, Matthew Lunning, Noopur Raje, Seema Singhal, Clayton Smith, George Somlo, Keith Stockerl-Goldstein, Steven P. Treon, Donna Weber, Joachim Yahalom, Dorothy A. Shead, and Rashmi Kumar

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM.

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Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry Anderson, Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Jason C. Chandler, Caitlin Costello, Yvonne Efebera, Matthew Faiman, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Yubin Kang, Malin Hultcrantz, Sarah Larson, Michaela Liedtke, Thomas Martin, James Omel, Kenneth Shain, Douglas Sborov, Keith Stockerl-Goldstein, Donna Weber, Jennifer Keller, and Rashmi Kumar

Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. This manuscript discusses the management of patients with solitary plasmacytoma, smoldering multiple myeloma, and newly diagnosed multiple myeloma.