Sagar Lonial, MD

In light of recent clinical trial data, key opinion leaders reflect on the appropriate selection of transplant for patients with newly diagnosed multiple myeloma.

Opening discussion on the management of transplant-eligible newly diagnosed multiple myeloma, expert panelists consider the role of quadruplet therapy and transplant in this setting.

Experts muse on the unmet needs of multiple myeloma, and exciting investigational therapies on the horizon.

A look at the role of bispecifics and CAR T-cell therapies in the multiple myeloma treatment landscape.

Experts discuss the case of a woman with relapsed/refractory multiple myeloma and the available treatment options, including novel BCMA-targeted agents.

Key opinion leaders describe the role of blood-based MRD testing in the transplant-ineligible multiple myeloma treatment landscape.

Nisha Joseph, MD, presents the case of a 78-year-old man with transplant-ineligible multiple myeloma and discusses treatment strategy.

Experts discuss how they define frail and high-risk patients with multiple myeloma and their treatment approaches for these patient populations.

An overview of the study design, efficacy, and safety findings of the MAIA trial.

Dr Nisha Joseph presents the case of a woman with transplant-ineligible multiple myeloma and discusses considerations when choosing frontline treatment regimens.

Drs Ajay Nooka and Jonathan Kaufman discuss maintenance and consolidation treatment strategies for transplant eligible multiple myeloma.

Experts discuss how they select a treatment regimen for a newly diagnosed multiple myeloma patient, and how they measure a successful treatment response.

A review of the study design and results of two clinical trials researching quadruplet therapies for newly diagnosed multiple myeloma presented at ASH 2021.

An overview of the currently available frontline treatment options for transplant-eligible multiple myeloma.

After reviewing the case of a patient with transplant-eligible newly-diagnosed multiple myeloma, experts consider optimal selection of first-line treatment.

Unfortunately, while survival outcomes with novel therapies have improved, the fraction of patients with multiple myeloma who are cured of their disease remains low. Immune therapies offer the hope for further improvement in outcomes and higher rates of cure.

In this article, we elucidate the rationale for use of novel drug combinations in patients with myeloma, and review current evidence-based data supporting the use of specific combinations in various settings. We also attempt to craft a framework to guide clinicians in optimizing the use of combination therapies, to enable patients to derive maximal benefit.

We discuss some of the anticipated multiple myeloma trials with Sagar Lonial, MD, ahead of the 2015 American Society of Clinical Oncology Annual Meeting.

Numerous small series of patients suggest that the prognosis for non-secretory myeloma patients is likely no worse than the prognosis for patients with traditional secretory myeloma, and in some settings may be superior.

The use of newer methods of disease assessment that focus on minimal residual disease may facilitate the long-term evaluation of IgD and IgE myeloma patients, even if the rare Ig subtype is not identified at diagnosis.

The introduction of new therapies has led to improved survival of patients with multiple myeloma (MM), even those with relapsed and/or refractory (R/R) disease.

The management of multiple myeloma (MM) has undergone rapid change with the recent emergence of several effective novel agents that have added complexity to individualized treatment decision-making. This paper reviews the initial management of 276 patients with MM diagnosed and treated by 43 US-based community oncologists since January 1, 2008. The case survey data obtained are evaluated within the broad context of published findings from major phase III randomized trials and as such reveal potential education gaps and implications for oncology CME. Overall, the results reveal that most patients were symptomatic at diagnosis and were risk-stratified by fluorescene in situ hybridization (FISH) and/or cytogenetics. When analyzed by age, the overall symptomatology and biomarker-defined risk profiles appeared similar in the three age groups studied (

Clinical outcomes data for all of oncology include those from trial after trial demonstrating poor outcomes in older patients with cancer. Whether these are the result of limited biologic reserve, poor performance status, or inherently worse biological disease at the time of diagnosis, such age-based disparities have continued unabated for decades. However, for the first time, older patients with multiple myeloma (MM) are starting to enjoy the kinds of remission durations and overall survival (OS) seen in younger patients. In this review by Dr. Harousseau, we see that through the use of regimens such as MPV (melphalan and prednisone plus bortezomib), MPT (melphalan and prednisone plus thalidomide), MPR (melphalan and prednisone plus lenalidomide), VMPT (bortezomib, melphalan, prednisone, and thalidomide), and Rd (lenalidomide and low-dose dexamethasone), we can begin to provide older patients with MM with a median OS approaching the 4- to 5-year mark-a far cry from the median OS of 2.5 to 3 years seen with MP just 15 years ago. So what are the remaining hurdles and challenges to be addressed in the upcoming 10 years?

New treatments and an improved biologic understanding of why malignant plasma cells are able to survive have dramatically changed the natural history of multiple myeloma. Along with these new treatments, therapeutic options for patients at each stage of their disease have become a collection of confusing consonants. Combinations such as Rd,[1] CRd,[2] VD,[3] VTD,[4] VRD,[5] CyBorD,[6] PAD,[7] and BiRD[8] all produce impressive response rates in the induction therapy setting, and can be used for patients with relapsed disease as well.

Our better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM—bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM.

Treatment options for patientswith myeloma have movedfrom the relatively ineffectivecombinations of cytotoxic agents andcorticosteroids, to the widespread useof high-dose therapy and autologousbone marrow or peripheral blood stemcell transplant. Through this transition,the overall survival for patientshas nearly doubled from a previousmedian survival of 2 to 2.5 years, upto 4 to 5 years based on the transplantarms of several large randomizedclinical trials.[1-3] In this issue ofONCOLOGY, Dr. Richardson andcolleagues extensively detail the recentadvances in myeloma therapythat involve the use of more “modern”or novel agents such as thalidomide(Thalomid), lenalidomide (Revlimid),and bortezomib (Velcade). Theseagents are of monumental importance in the assault on myeloma as theyhave provided much needed advancesfor patients with relapsed and refractorymyeloma and, in doing so,have set the stage for the next majorrevolution in myeloma therapy.

The graft-vs-tumor effect is an important part of the curative potential of allogeneic transplantation. We characterized the effect of transplanted donor mononuclear cells on relapse- and event-free survival after allogeneic bone marrow transplantation (BMT). We studied 113 consecutive patients with hematologic malignancies who received non-T-cell-depleted BMT from human leukocyte antigen (HLA)-matched siblings. Most patients (n = 103) received busulfan (Myleran)-based conditioning, and all patients received standard short-course methotrexate and tacrolimus (Prograf) as graft-vs-host disease prophylaxis. Sixty-four patients had low-risk diagnoses (acute lymphoblastic leukemia/acute myeloid leukemia [first complete remission], myelodysplastic syndrome [refractory anemia/refractory anemia with ring sideroblasts], and chronic myeloid leukemia [first chronic phase]); 49 patients had high-risk diagnoses (all others). Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3-positive T cells, CD34-positive hematopoietic cells, and type 2 dendritic cells (DC2) as covariates for event-free survival, relapse, and nonrelapse mortality. Recipients of larger numbers of DC2 cells had significantly lower event-free survival, a lower incidence of chronic graft-vs-host disease, and an increased incidence of relapse. Recipients of larger numbers of CD34-positive cells had improved event-free survival; recipients of fewer CD34-positive cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, content of donor DC2 cells was associated with decreased chronic graft-vs-host disease and graft-vs-leukemia effects consistent with Th2/Tc2 polarization of donor T cells following allogeneic bone marrow transplantation. [ONCOLOGY 16(Suppl 1):19-26, 2002]