A panel of expert hematologic-oncologists offer insights on how they treat patients with multiple myeloma at early relapse.

Treatment of Multiple Myeloma at Early Relapse

 featuring Krina K. Patel, MD, MSc; Amrita Krishnan, MD; Caitlin Costello, MD; Saad Z. Usmani, MD, MBA, FACP; and Rafat Abonour, MD.

The discussion focuses on treatment selection in early relapse multiple myeloma after initial therapy. Key factors include patient comorbidities, pace of relapse, high-risk features, prior toxicity, and duration of benefit from prior lines. Refractoriness to lenalidomide maintenance is increasingly common and complicates choices.

For standard-risk relapsed patients, triplet regimens like carfilzomib-cyclophosphamide-dexamethasone (KCd) or carfilzomib-daratumumab-dexamethasone (DKd) are recommended based on efficacy data from the phase 3 CANDOR and IKEMA trials vs doublets. However, in frail, older patients, combinations like daratumumab-pomalidomide-dexamethasone (DPd) or isatuximab-pomalidomide-dexamethasone (IPd) may be better tolerated while still improving outcomes over pomalidomide-dexamethasone.

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The expert panel discusses how the standard of care for transplant-ineligible NDMM has evolved and reviews recent updates in this space.

The Evolving Treatment Paradigm for Transplant Ineligible MM

The discussion focuses on initial treatment approaches for transplant-ineligible multiple myeloma patients. Historically, doublet regimens were used, but data now supports triplet regimens like lenalidomide-bortezomib-dexamethasone (RVd) and daratumumab (dara) plus RVd as superior for progression-free and overall survival, with manageable toxicity. The phase 3 SWOG trial is comparing Dara-lenalidomide-dexamethasone and RVd triplets. Adding anti-CD38 monoclonal antibodies to lenalidomide-based triplets as quadruplet regimens further improves responses.

Results from the phase 3 IsKia trial adding isatuximab to RVd were recently announced, demonstrating improved progression-free survival vs RVd alone. Balancing efficacy, toxicity, quality of life, and goals of care is still needed, especially in frailer patients where depth of response may not correlate with clinical benefit. Ongoing studies are evaluating quadruplet safety and efficacy specifically in frail, elderly transplant-ineligible populations.

Safety and Clinical Experience of XPO1 Inhibitors in R/R MM Patients

Dr. Usmani, MD, MBA, FACP provides insights into Selinexor's safety profile in Relapsed/Refractory Multiple Myeloma (R/R MM), comparing it with other treatments and delve into the ongoing challenges and unmet needs in R/R MM patient care.

Treatment Strategies in Triple Class Refractory MM Patients 

An expert explores factors influencing the selection of treatment regimens in relapsed, triple class refractory multiple myeloma (MM) patients, with a focus on prophylactic measures for managing adverse events associated with novel agents like Selinexor, bispecific, and CAR-T therapies. 

Treatment Strategies in Triple Class Refractory MM Patients

Amrita Krishnan, MD, and Saad Usmani, MD, MBA, FACP, offer their perspectives on the role of stem cell transplant and MRD testing in patients with NDMM.

Role of Transplant and MRD in Newly Diagnosed MM

The discussion focuses on determining which newly diagnosed multiple myeloma patients should proceed to autologous stem cell transplant (ASCT) vs an induction-maintenance approach without ASCT. For high-risk patients, ASCT remains standard, but for standard-risk patients who achieve minimal residual disease (MRD) negativity with quadruplet induction, omitting transplant with prolonged maintenance therapy is reasonable. However, attaining MRD negativity from induction alone may not be enough, and sustained MRD negativity over time is ideal. There is also concern about declining health and stem cell collection feasibility with increasing patient age.

While historically ASCT with high-dose melphalan was considered the best antimyeloma therapy, novel agents now appear equally if not more efficacious. Still, ASCT improves initial progression-free survival.

Amrita Krishnan, MD, and Saad Z. Usmani, MD, MBA, FACP, offer their perspectives on the role of stem cell transplant and MRD testing in patients with newly diagnosed multiple myeloma.

Clinical insights on the definition of high-risk multiple myeloma and the treatment of patients with high risk disease.

Advances in the Treatment of High-Risk MM

The group discusses early results from the IsKia trial presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition evaluating isatuximab plus carfilzomib, lenalidomide, and dexamethasone (KRd) vs KRd alone in newly diagnosed, transplant-eligible multiple myeloma patients. Similar to prior studies with daratumumab, the quadruplet regimen including isatuximab showed high minimal residual disease negativity rates, suggesting deep and durable responses can be achieved by adding CD38 antibodies to triplet regimens pre- and post-transplant.

The discussion then shifts to defining high-risk multiple myeloma, which is associated with worse progression-free and overall survival outcomes. High-risk disease is defined by the International Myeloma Working Group as having certain cytogenetic abnormalities like 1q amplification, 17p deletions, or other translocations. Ultrahigh-risk disease is present when patients have 2 or more high-risk cytogenetics. With aggressive quadruplet induction and consolidation, remission rates can improve even in high-risk patients, but sustaining minimal residual disease negativity remains challenging. Ongoing trials are evaluating whether tandem autologous stem cell transplantation may further improve durable responses.

Clinical insights on the definition of high-risk multiple myeloma and the treatment of patients with high risk disease, including how the results from the IsKia trial might impact practice.

Experts in multiple myeloma discuss highlights from the ASH 2023 meeting around transplant-eligible NDMM.

Highlights from ASH 2023 in Transplant-Eligible NDMM

The experts discuss recent study results presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition regarding adding daratumumab to standard triplet induction, transplant consolidation, and maintenance therapy for newly diagnosed, transplant-eligible multiple myeloma patients.

The GRIFFIN trial showed improved stringent complete response rates with quadruplet induction including daratumumab vs triplet induction. The PERSEUS trial confirmed these findings in a larger phase 3 study, demonstrating improved progression-free survival at 4 years (84% vs 67%) and higher complete response and minimal residual disease negativity rates with quadruplet induction and maintenance including daratumumab. However, it is unclear if the benefit is from induction alone or requires continuous daratumumab therapy.

In real-world practice, consolidation post transplant and doublet maintenance is not universally used. The question remains if quadruplet induction alone is sufficient or if daratumumab should be incorporated into maintenance as well, especially for high-risk patients who may derive more benefit. Ongoing studies like the SWOG S1803 trial will provide more evidence regarding optimal maintenance strategies.

Experts in multiple myeloma discuss highlights from the ASH 2023 meeting around transplant-eligible NDMM with particular focus on the PERSEUS and GRIFFIN trials and the clinical implications of the results of these studies.

Evolving Role of XPO1 Inhibitors in Multiple Myeloma

Saad Usmani, MD, MBA, FACP, discusses the updates of XPO1 inhibitors in relapsed/refractory multiple myeloma patients.

Role of XPO1 Inhibitors in the Treatment of Relapsed/Refractory Multiple Myeloma 

A panel of experts discuss the evolving landscape of newly diagnosed multiple myeloma.

The Evolving Landscape of Newly Diagnosed Multiple Myeloma

Patel provides an overview of recent developments in treating newly diagnosed multiple myeloma patients. The distinction between transplant-eligible vs ineligible is blurring, with some fit patients choosing to defer transplant. Triplet regimens have shifted to quadruplet regimens incorporating anti-CD38 monoclonal antibodies like daratumumab or isatuximab. Studies like GRIFFIN and PERSEUS show quadruplet regimens improve responses over triplets for both standard-risk and high-risk transplant-eligible patients.

For transplant-ineligible/frail patients, lenalidomide-bortezomib-dexamethasone (RVd) remains an option, but daratumumab-lenalidomide-dexamethasone (DRd) based on the MAIA trial may provide an even longer treatment-free interval. For high-risk transplant-ineligible patients, a quadruplet approach with RVd plus daratumumab is also being studied.

A key goal of therapy has become attaining minimal residual disease (MRD) negativity, which is associated with improved progression-free and overall survival. The depth of response seen with quadruplet regimens may help support regulatory approval of MRD as a biomarker for novel agents.

Saad Usmani, MD, MBA, FACP, FASCO

Articles

Treatment of Multiple Myeloma at Early Relapse

The Evolving Treatment Paradigm for Transplant Ineligible MM

Safety and Clinical Experience of XPO1 Inhibitors in R/R MM Patients

Treatment Strategies in Triple Class Refractory MM Patients

Role of Transplant and MRD in Newly Diagnosed MM

Advances in the Treatment of High-Risk MM

Highlights from ASH 2023 in Transplant-Eligible NDMM

Role of XPO1 Inhibitors in the Treatment of Relapsed/Refractory Multiple Myeloma

The Evolving Landscape of Newly Diagnosed Multiple Myeloma