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Release Date: April 30, 2019
Expiration Date: April 30, 2020
Media: Internet - based
The treatment landscape for hematologic malignancies such as multiple myeloma and non-Hodgkin lymphoma is evolving at a rapid pace. Hematopoietic stem cell transplantation (HSCT) has remained a cornerstone approach for the management of many patients with these conditions, but questions remain concerning the timing of HSCT use and how newer frontline treatment regimens may influence transplantation decisions. Furthermore, techniques for optimal stem cell mobilization are continuing to be investigated, with the goals of minimizing the burden on the patient and maximizing the likelihood of successful stem cell collection for anticipated procedures.
This continuing medical education activity will help you address these and other challenges that you may be facing with your patients. Featuring commentary from clinical experts in the field of hematopoietic stem cell transplantation, this educational initiative will help you apply the data effectively to the management of your patients who may be candidates for HSCT. Key decision points pertaining to transplantation and stem cell mobilization will be reviewed in depth.
This activity is supported by an educational grant from Sanofi Genzyme.
Instructions for This Activity and Receiving Credit
This educational program is directed toward hematologists, medical oncologists, and researchers/investigators who treat or are interested in the treatment of hematologic malignancies. Other allied healthcare professionals, including nurse practitioners, physician assistants, and nurses involved in the treatment and management of patients with hematologic malignancies, are also invited to participate.
Upon successful completion of this educational program, you should be better prepared to:
Shaji K. Kumar, MD
Professor of Medicine
Consultant, Division of Hematology, Department of Internal Medicine
Disclosures: Grant Research/Support: AbbVie, Amgen (to institution), Bristol-Myers Squibb, Celgene, Genentech, Kite, MedImmune, Merck, Novartis, Roche-Genentech, Sanofi, Takeda; Consultant: AbbVie, Celgene (with no personal payments), Genentech, Janssen, Kite, MedImmune, Merck, Takeda.
Sergio A. Giralt, MD
Professor of Medicine
Weill Cornell Medical College
Chief Attending Physician, Adult Bone Marrow Transplant Service
Melvin Berlin Family Chair in Myeloma Research
Memorial Sloan Kettering Cancer Center
New York, NY
Paul Shaughnessy, MD
Program Medical Director
Blood and Marrow Transplant
Texas Transplant Institute
San Antonio, TX
Disclosures: Consultant: Advisory Board: Amgen, Sanofi, Takeda; Speakers’ Bureau: Kite, Sanofi, Takeda.
Sergio A. Giralt; the staff of Physicians’ Education Resource®, LLC; and The Medical College of Wisconsin have no relevant financial relationships with commercial interests to disclose.
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Considerations for Successful Stem Cell Mobilization
There are several criteria for a successful stem cell collection. It should mobilize a sufficient number of cells capable of prompt and durable hematopoietic reconstitution, and achieve adequate neutrophil and platelet engraftment, with rapid recovery of hematopoietic function.1-3 Based on retrospective data, patients who receive <1 x 106 CD34+ cells/kg have a high incidence of poor platelet recovery, whereas those who receive ≥2 x 106 CD34+ cells/kg have adequate hematopoietic engraftment. The American Society for Blood and Marrow Transplantation and other guideline-issuing organizations have established the latter value as the minimum threshold for transplantation.4,5 The majority of patients receiving >2.5 x 106 CD34+ cells/kg experience durable neutrophil engraftment by day 18, and a level of 5 x 106 CD34+ cells/kg has been associated with rapid platelet engraftment.6,7
Some factors associated with poor mobilization outcomes are an elevated number of cycles/duration of prior chemotherapy, female gender, age ˃60 years, low platelet count, and exposure to such medications as fludarabine, platinum-based chemotherapy, bendamustine, or lenalidomide. Insufficient collection of stem cells may result in several poor outcomes, such as more days of apheresis, bone marrow harvesting, and ineligibility for transplantation. Use of a suboptimal apheresis product may lead to delayed, partial, or failed stem cell engraftment,8 as well as increased need for transfusions.9
Collection of an adequate number of CD34+ cells has been associated with more-rapid recovery of platelet function.10 A retrospective analysis of patients with multiple myeloma or non-Hodgkin lymphoma showed that platelet recovery was robust when the CD34+ cell dose transplant was ≥4 x 106/kg. No significant difference in benefit was shown between groups receiving 4 to 6 x 106 CD34+ cells/kg and those receiving ≥6 x 106 CD34+ cells/kg.11 Successful stem cell mobilization has also been associated with lower transplant-related costs. Patients who undergo transplantation with a quality stem cell mobilization spend less time in the hospital for their transplantations.12
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Updates on Stem Cell Mobilization and Transplant for Multiple Myeloma
The number of patients undergoing stem cell transplantation (SCT) for multiple myeloma (MM) in the United States is increasing. One recent estimation reported more than 8000 transplants for MM/plasma cell disorders, with the majority of these being autologous stem cell transplants (ASCTs).1 The role of upfront ASCT continues to evolve. New medications, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, have the potential to generate deep responses with initial therapy. Data from the IFM 2009 trial continue to support the role of transplantation. In this study, patients with MM were randomized to receive induction with 3 cycles of RVD (lenalidomide, bortezomib, dexamethasone) consolidation therapy, with either 5 more cycles of RVD or ASCT plus high-dose melphalan followed by 2 more cycles of RVD.2 Patients who underwent transplantation had a significantly greater median progression-free survival than those who did not (50 vs 36 months; HR, 0.65; P <.001). Patients receiving a transplant also had a significantly greater rate of complete response (59% vs 48%; P =.03), as well as a greater percentage of cases where minimal residual disease was not seen (79% vs 65%; P <.001).2 There was no difference in overall survival (OS).2
The introduction of plerixafor was supported by findings from initial studies that demonstrated an increased likelihood of collecting a designated target of 6 x 106 CD34+ cells/kg with a combination of plerixafor and granulocyte colony-stimulating factor (G-CSF) compared with placebo and G-CSF. This advantage was demonstrated on each day of stem cell collection.3,4 When chemotherapy was compared with the combination of growth factor and plerixafor in a retrospective analysis, patients who received cyclophosphamide had lower rates of successful mobilization and collection (78% vs 98%; P <.01); a greater incidence of complications requiring hospitalization (30% vs 2%; P <.01); and greater average cost per patient successfully completing mobilization.5 Studies have also assessed the role of salvage transplantation for patients with MM. In one randomized study of patients with relapsed/refractory MM, patients who received salvage ASCT compared with a chemotherapy-based approach had improved OS at first relapse; delay of ASCT to treatment in the third line or later may not provide the same degree of benefit.6 Repeat mobilization is possible for patients with MM. Multiple aphereses may be required, with regimens involving a combination of G-CSF and plerixafor frequently yielding a successful stem cell collection.7
Guidelines for approaches to stem cell mobilization have been established. Among the key goals are reduction of overall failure rates to below 5%, minimization of mobilization-associated complications, and optimization of resource utilization.8 Pre-apheresis peripheral blood CD34+ cell count monitoring may help to identify poor mobilizers and to trigger additional measures for mobilization enhancement. Upfront steady-state mobilization with plerixafor plus G-CSF may help to reduce the need for remobilization.8 The combination of chemomobilization plus plerixafor plus G-CSF has been studied and is the subject of ongoing clinical investigation.8 With respect to remobilization, the use of cytokine therapy alone has a high likelihood of failure, and incorporation of other options, such as plerixafor and chemomobilization, should be considered.
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Updates in Mobilization of Lymphoid Malignancies
Stem cell transplantation (SCT) may be used for a wide variety of lymphoid malignancies, including aggressive B-cell non-Hodgkin lymphoma (NHL), follicular NHL, mantle cell lymphoma (MCL) in first complete remission, peripheral T-cell lymphoma in first complete remission, and Hodgkin lymphoma (HL). Patients with these malignancies may have different treatment histories and salvage therapies that may impact timing and ability to mobilize autologous hematopoietic stem cells. Patients with recurrent diffuse large B-cell lymphoma (DLBCL) may have a poor prognosis, even with aggressive salvage and autologous stem cell transplantation (ASCT). If patients are chemosensitive to salvage therapy, survival outcomes are better than those for patients who are chemoresistant.1,2 Chimeric antigen receptor (CAR) T-cell therapy is being evaluated in the management of patients with DLBCL as an alternative to ASCT.
Currently, chemotherapy stem cell mobilization approaches for patients with NHL do not differ significantly from cytokine stem cell mobilization approaches with respect to disease-free survival (DFS) or overall survival (OS) outcomes.3-5 The choice of mobilization approaches, as with multiple myeloma (MM), often depends on patient-related and logistical factors. Center-specific capabilities are also factors, including the ability to obtain flow cytometry results of peripheral blood CD34+ cell counts, weekend staffing after chemomobilization, and familiarity of staff with tracking and planning different mobilization regimens.
Several retrospective studies have compared chemotherapy versus cytokine-based mobilization strategies. A recent study from the University of Wisconsin and the University of West Virginia retrospectively evaluated standard RICE (rituximab, ifosfamide, carboplatin, etoposide) chemotherapy mobilization versus a scheduled granulocyte colony-stimulating factor (G-CSF)/plerixafor mobilization versus an algorithm-based plerixafor mobilization for patients with HL and NHL. In this study, more stem cells were collected in the group receiving chemotherapy mobilization; however, this group was younger and less heavily treated than the other groups of patients.6 Ultimately, no differences in DFS or OS were seen in this study.6
There is concern that some chemotherapy agents may have a negative impact on stem cell mobilization for patients with lymphoid malignancies. Bendamustine has been shown to adversely affect stem cell mobilization in patients with MCL.7,8 Other agents, such as bortezomib, may actually facilitate stem cell mobilization for patients with MCL.9 Paclitaxel may be an option to consider, as well.10
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May 30, 2019
May 31, 2019
Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing Strategies
May 31, 2019
May 31, 2019