The Path Forward in Multiple Myeloma: 2021 Jan Waldenstrom Award Lecture (2023)

Section snippets

Lessons from Key Publications

There are specific insights that I have gained through my work with esteemed colleagues on key papers that have been invaluable and worth reflection. At the top of the list are studies on the prevalence and prognosis of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).1, 2, 3, 4, 5, 6 These studies provide a roadmap for how specific disease entities are defined and characterized. In order to establish a disease entity, these studies illustrate the

The Path Forward

Clearly, we have made remarkable progress in the field. We have updated disease definition,10 staging,15 and response assessment.16 A number of new drugs including exciting immunotherapy interventions hold a lot of promise. Supportive care measures have lowered the impact of bone disease and renal failure. But we can have a bigger impact if we tackle some additional areas of research that we now have the opportunities and tools to address. I will conclude by listing some of these things we need

Authorship Contribution Statement

SVR conceived of the paper, researched the literature, and wrote the manuscript.


SVR declares no conflict of interest.


Supported in part by grants CA 168762, and CA186781 from the National Cancer Institute, Rockville, MD, USA, and the Marvin Family Grant.

  • Research article

    PD-1 Blockade After Avelumab in Relapsed/Refractory Classical Hodgkin Lymphoma

    Clinical Lymphoma Myeloma and Leukemia, Volume 22, Issue 10, 2022, pp. e893-e897

    Anti-PD-1 directed therapy is safe and effective in patients with relapsed/refractory (r/r) cHL and is currently being studied in the frontline setting. There are currently little data regarding the safety and efficacy of PD-1 blockade after prior PD-L1 blockade with agents such as avelumab.

    This is a retrospective case series evaluating r/r cHL patients treated with avelumab who subsequently received at least 1 dose of PD-1 blockade. Primary objective is efficacy as measured by overall response rate. Secondary objectives include duration of response and time to progression on PD-1 blockade as well as safety as evaluated by incidence and severity of immune-related adverse events (irAE) with PD-1 blockade.

    There were 7 patients treated with PD-1 blockade after avelumab, of whom 4 were re-treated. The median follow-up was 46.8 months. At the time of PD-1 blockade initiation median age was 36.6 years, all patients had advanced stage, 1 patient had B symptoms, and 4 patients had extranodal disease. Patients received median 7 prior lines of therapy including avelumab. Median duration on anti-PD-1 treatment was 15.9 months. A response was observed in 86% of patients with median duration of response of 26.4 months and median time to progression of 22.2 months. Only 1 patient experienced an irAE (grade 2 pneumonitis).

    Our study suggests that PD-1 blockade after PD-L1 blockade in r/r cHL appears safe and may be effective with durable responses observed in a subset of patients.

  • Research article

    “Diffuse Large B-Cell Lymphoma in the Elderly: Real-World Outcomes From a Developing Country”

    Clinical Lymphoma Myeloma and Leukemia, Volume 22, Issue 10, 2022, pp. e898-e906

    Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) in the elderly aims to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in the elderly is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients with cardiac contraindications or anticipated severe toxicities to anthracyclines.

    We retrospectively analyzed the treatment outcomes of patients, aged 60 years and above, newly diagnosed with DLBCL at our center. Of a total of 218 patients, 71 patients received the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) and 137 received R-CE (Etoposide) OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the performance status, cardiac comorbidities and frailty as well as available resources for supportive care.

    The 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, P-value < .001) and this superiority of R-CHOP was seen in both early and advanced disease. The incidence of febrile neutropenia and grade III/IV hematological toxicities was significantly higher in the R-CHOP group in the age group of 60 to 65 years’. ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for 2-year PFS rate by multivariate analysis.

    Anthracycline-based regimen should be used in elderly fit patients without absolute cardiac contraindications wherever feasible with adequate access to supportive care.

  • Research article

    Tumor Infiltrating Lymphocytes Predict Survival in Solid Organ Transplant Recipients With Monomorphic Post-transplant Lymphoproliferative Disorders

    Clinical Lymphoma Myeloma and Leukemia, Volume 22, Issue 10, 2022, pp. 744-752

    The tumor microenvironment (TME) in post-transplant lymphoproliferative disorders (PTLDs) remains unexplored. Tumor infiltrating lymphocytes (TILs) are prognostic in other lymphomas. We assessed the prognostic impact of TILs in monomorphic B-cell PTLD.

    TIL density (CD3+ cells/mm2) was determined by CD3 immunohistochemistry in archived diagnostic biopsies from patients diagnosed with monomorphic B-cell PTLD.

    Amongst monomorphic PTLDs (N=107), low TIL-count was associated with inferior 2-year progression-free survival (PFS) (41% versus 86%, P=.003) and 2-year overall survival (OS) (52% versus 93%, P=.003) by Kaplan-Meier analysis. Low TIL-count was significant on Cox univariate regression for inferior PFS (HR 4.5, 95% CI 2.0-9.9, P < .001) and OS (HR 4.6, 95% CI 1.8-11.8, P < .001). Multivariate analysis with clinical variables (age ≥60 years, high LDH, stage III/IV, CNS involvement) and TIL-count showed significance for PFS (HR 3.3, 95% CI 1.3-8.3, P=.010) and a non-significant trend for OS (HR 2.6, 95% CI 0.9-7.3, P=.064). A composite score including TILs and clinical variables (age ≥60 years, high LDH, stage III/IV, CNS involvement) effectively stratified monomorphic PTLD patients by PFS and OS (2-year OS: low-risk 93%, intermediate-risk 61%, high-risk 23%, P < .001).

    The TME and TILs are prognostically relevant in monomorphic PTLD. Prognostic models including measures of the TME may improve risk stratification for patients with monomorphic PTLDs.

  • Research article

    SOHO State of the Art Updates and Next Questions | Beyond BCL-2 Inhibition in Acute Myeloid Leukemia: Other Approaches to Leverage the Apoptotic Pathway

    Clinical Lymphoma Myeloma and Leukemia, Volume 22, Issue 9, 2022, pp. 652-658

    BCL-2 inhibition has transformed the therapeutic landscape of acute myeloid leukemia (AML) but is not curative for the majority of patients. Consequently, there has been growing interest in targeting other facets of the apoptotic machinery to improve outcomes. These approaches include targeting the intrinsic and extrinsic apoptotic pathway, inducing apoptosis via p53 activation, and others. Targeting the intrinsic apoptotic pathway includes MCL-1 antagonism and BCL-xL inhibition. MCL-1 can be targeted via direct inhibitors as well as via indirect mechanisms to downregulate MCL-1 including inhibition of cyclin dependent kinases and Nedd8 activating enzyme. The extrinsic apoptotic pathway could be harnessed via inhibition of inhibitor of apoptosis proteins, agonism of the TNF-related apoptosis-inducing ligand receptors and inhibiting FLICE-like inhibitor protein. Approaches inducing p53-mediated apoptosis are being evaluated using inhibitors of MDM2, dual inhibitor of MDM2/X in TP53 wild-type AML and p53 reactivators in TP53-mutant myeloid disorders. Several such agents are in early clinical development and rationale combinations of these agents may help improving outcomes for patients with AML.

  • Research article

    Long-Term Complete Clinical and Hematological Response With Bortezomib: The Report of a Case With TEM(P)I Syndrome and a Review of the Literature

    Clinical Lymphoma Myeloma and Leukemia, Volume 22, Issue 9, 2022, pp. 702-707

    TEMPI syndrome was first defined in 2011 and classified as a plasma cell neoplasm with associated paraneoplastic syndrome in 2016. The pathogenesis of the syndrome is not well understood. Recognition of a combination of telangiectasia, erythrocytosis with a high erythropoietin level, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunt is the first step in managing the disease. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other dermatological, renal, and pulmonary disorders. Without early diagnosis significant disability results from the pulmonary damage. The article we present here describes a clinical case of TEMPI-syndrome in a 58-year-old woman, which illustrates the difficulties associated with the timely recognition of this unusual disease. Here, we also review the clinical features of TEMPI syndrome, differential diagnosis and available treatment options, based on current literature. Although limited in number, with the addition of new patients to the literature, TEMPI syndrome is evolving into a well characterized multisystem syndrome. This rare disorder should not be missed, especially if the patient has a putative diagnosis of essential telangiectasia with a monoclonal gammopathy and polistemia. Increasing the awareness of clinicians about the disease and adding new patient data to the literature may contribute to a better understanding of the pathophysiology of the disease and standardization of treatment.

  • Research article

    SOHO State of the Art Updates and Next Questions | Myeloid/Lymphoid Neoplasms with Eosinophilia and Gene Rearrangements: Diagnostic Pearls and Pitfalls

    Clinical Lymphoma Myeloma and Leukemia, Volume 22, Issue 9, 2022, pp. 643-651

    The myeloid and/or lymphoid neoplasms with eosinophilia and gene rearrangement (MLN-Eos) are a rare group of hematopoietic neoplasms with diverse and often perplexing presentations that can cause challenges, and even potential pitfalls, for the diagnostic pathologist. However, accurate diagnosis of this group of disorders is of the utmost importance, since the presence of specific gene rearrangements dictates targeted patient therapy. The goal of this review is to discuss the current literature, including emergence of novel molecular data, and equip pathologists and clinicians with morphologic and immunophenotypic clues for diagnosing this challenging group of hematopoietic neoplasms.

© 2022 Elsevier Inc. All rights reserved.

Top Articles
Latest Posts
Article information

Author: Roderick King

Last Updated: 02/04/2023

Views: 6134

Rating: 4 / 5 (71 voted)

Reviews: 86% of readers found this page helpful

Author information

Name: Roderick King

Birthday: 1997-10-09

Address: 3782 Madge Knoll, East Dudley, MA 63913

Phone: +2521695290067

Job: Customer Sales Coordinator

Hobby: Gunsmithing, Embroidery, Parkour, Kitesurfing, Rock climbing, Sand art, Beekeeping

Introduction: My name is Roderick King, I am a cute, splendid, excited, perfect, gentle, funny, vivacious person who loves writing and wants to share my knowledge and understanding with you.