With so many recent advances in relapsed/refractory multiple myeloma, keeping abreast with current treatment recommendations can be challenging. Novel immunomodulators, proteasome inhibitors, monoclonal antibodies, histone deacetylase inhibitors, and nuclear export inhibitors have all been added to the armamentarium, and the choice of which of these drugs or drug combinations to use depends on individual disease-related and patient-related factors, previous therapies, and treatment toxicities. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Jorge J. Castillo provided an overview of the myriad treatments available for patients with relapsed/refractory multiple myeloma, as well as therapies on the horizon.
Evolution of Therapy for Relapsed/Refractory Multiple Myeloma
Jorge J. Castillo
Risk Factors for Early Death After Rituximab-Based Immunochemotherapy in Older Patients With Diffuse Large B-Cell Lymphoma
Adam J. Olszewski, Kalyan C. Mantripragada, and Jorge J. Castillo
Background: Older patients with diffuse large B-cell lymphoma (DLBCL) are at risk of severe chemotherapy-related morbidity and mortality. Our objective was to quantify the risk and identify factors associated with death during the first cycle of immunochemotherapy in this population. Patients and Methods: Using Medicare claims linked to the population-based SEER registry (SEER-Medicare), we studied patients with DLBCL aged 65 years and older who received immunochemotherapy containing rituximab, cyclophosphamide, and vincristine, in combination with doxorubicin, mitoxantrone, or etoposide in 2003–2012. Risk factors for death and hospitalization within the first 30 days of treatment were studied in multivariable logistic regression models. Results: We identified 5,530 patients with a median age of 76 years, of whom 94% received doxorubicin-containing immunochemotherapy. Granulocyte colony-stimulating factor (G-CSF) was administered to 66% of patients during the first treatment cycle. Cumulative incidence of death at day 30 was 2.2%. The risk was significantly higher in patients aged 75 years and older and those who had B symptoms, chronic kidney disease, poor functional status, use of walking aids or wheelchairs, and prior hospitalization or upper endoscopy. The group with 0 to 1 risk factors (56% of patients) had a very low (0.6%) risk of early death, whereas the group with 4 or more risk factors (6% of patients) had a risk of 8.3%. Receipt of G-CSF was associated with a lower probability of early death in the high-risk group. The incidence of hospitalization within the first 30 days was 23.5%, peaking at day 8 of the cycle. Conclusions: Among older patients with DLBCL who receive contemporary immunochemotherapy, 1 in 45 die during the first month of treatment, and 1 in 4 are hospitalized. Factors identifiable from administrative/electronic records can stratify this risk and could be incorporated into decision support tools. Prophylactic G-CSF is not administered to more than one-third of patients, indicating an opportunity for improved preventive interventions.
Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma
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.
NCCN Guidelines® Insights: Multiple Myeloma, Version 3.2022
Featured Updates to the NCCN Guidelines
Natalie S. Callander, Muhamed Baljevic, Kehinde Adekola, Larry D. Anderson Jr, Erica Campagnaro, Jorge J. Castillo, Caitlin Costello, Srinivas Devarakonda, Noura Elsedawy, Matthew Faiman, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Malin Hultcrantz, Yubin Kang, Sarah Larson, Michaela Liedtke, Thomas Martin, James Omel, Douglas Sborov, Kenneth Shain, Keith Stockerl-Goldstein, Donna Weber, Ryan A. Berardi, Rashmi Kumar, and Shaji K. Kumar
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.
NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020
Featured Updates to the NCCN Guidelines
Shaji K. Kumar, Natalie S. Callander, Jens Hillengass, Michaela Liedtke, Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Jason C. Chandler, Robert F. Cornell, Caitlin Costello, Yvonne Efebera, Matthew Faiman, Alfred Garfall, Kelly Godby, Leona Holmberg, Myo Htut, Carol Ann Huff, Yubin Kang, Ola Landgren, Ehsan Malek, Thomas Martin, James Omel, Noopur Raje, Douglas Sborov, Seema Singhal, Keith Stockerl-Goldstein, Carlyn Tan, Donna Weber, Alyse Johnson-Chilla, Jennifer Keller, and Rashmi Kumar
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1.2020 version of the NCCN Guidelines for Multiple Myeloma.
Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology
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.
Systemic Light Chain Amyloidosis, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology
Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry D. Anderson Jr., Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Caitlin Costello, Christopher D’Angelo, Srinivas Devarakonda, Noura Elsedawy, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Malin Hultcrantz, Yubin Kang, Sarah Larson, Hans C. Lee, Michaela Liedtke, Thomas Martin, James Omel, Aaron Rosenberg, Douglas Sborov, Jason Valent, Ryan Berardi, and Rashmi Kumar
Primary systemic light chain amyloidosis (SLCA) is characterized by production of light chains that get converted to amyloid fibrils with an affinity for visceral organs and causing organ dysfunction. The therapy for SLCA is directed to recovering the function of the affected organs by targeting the abnormal plasma cell clone and slowing deposition of amyloid fibrils. The NCCN Guidelines for SLCA provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated SLCA.
NCCN Guidelines Insights: Multiple Myeloma, Version 3.2018
Shaji K. Kumar, Natalie S. Callander, Melissa Alsina, Djordje Atanackovic, J. Sybil Biermann, Jorge Castillo, Jason C. Chandler, Caitlin Costello, Matthew Faiman, Henry C. Fung, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Yubin Kang, Adetola Kassim, Michaela Liedtke, Ehsan Malek, Thomas Martin, Vishala T. Neppalli, James Omel, Noopur Raje, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Donna Weber, Joachim Yahalom, Rashmi Kumar, and Dorothy A. Shead
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, evaluation, treatment, including supportive-care, and follow-up for patients with myeloma. These NCCN Guidelines Insights highlight the important updates/changes specific to the myeloma therapy options in the 2018 version of the NCCN Guidelines.