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Challenges and Opportunities in Multiple Myeloma

Challenges and Opportunities in Multiple Myeloma

Multiple Myeloma, a cancer of the plasma cells, remains a formidable adversary in the realm of oncology. This special theme issue is dedicated to unraveling the complexities of Multiple Myeloma, presenting the latest research on its pathophysiology, treatment breakthroughs, and patient care strategies. It aims to shed light on the challenges faced by patients and healthcare providers, while also showcasing the innovative approaches that offer new hope. From cutting-edge therapies to discussions on improving quality of life, this issue encapsulates the dynamic landscape of Multiple Myeloma, offering insights and fostering discussions that could pave the way for future advancements in the field.

Poy Theprungsirikul, MD
Clinical Fellow, Yale School of Medicine, Yale University, New Haven, CT, USA

Natalia Neparidze, MD
Associate Professor of Internal Medicine (Hematology); Research Leader, Myeloma Program, Hematology, Yale School of Medicine, Yale University, New Haven, CT, USA

Abstract

Cancer has been recognized as one of the major comorbidities associated with severe outcomes in the novel coronavirus disease 19 (COVID-19) patients. Compared to those with solid tumors and those without cancer, patients with hematologic malignancies appear to have more severe clinical outcomes and higher rate of mortality from COVID-19. This was particularly demonstrated during the early pandemic period. The COVID-19 pandemic has posed additional challenges in the management of hematologic malignancies, including establishing prompt diagnoses, providing optimal treatment while minimizing the risk and sequela of COVID-19 infection. Given these challenges, clinical practice guidelines and recommendations on management of hematologic malignancies during the COVID-19 pandemic were developed and proposed based on expert panels and individual expert opinions. Multiple myeloma is the second most common hematologic malignancy. The management of patients with multiple myeloma during the COVID-19 pandemic is extremely challenging as patients with multiple myeloma are particularly vulnerable to infections due to underlying humoral and cellular immune dysfunction, cytotoxic chemotherapy, immunotherapy, cellular therapy and steroid regimens, advanced age, and the presence of other comorbidities. In this paper, we attempt to provide a general review of clinical practice management patterns during and after the COVID-19 pandemic in patients with multiple myeloma and demonstrate how changes evolved as more knowledge was gained over time. Specifically, we review the impact of the pandemic on treatment approaches, supportive care, and vaccinations for patients with newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, patients with stable disease, and those with precursor states like monoclonal gammopathy and smoldering multiple myeloma. During early pandemic several changes were noted in myeloma care including minor delay in time to treatment initiation and tendency to defer autologous stem cell transplant. However, after 2022, with the advent of effective vaccines and treatment strategies the severity of COVID-19 infection decreased and care of myeloma returned to usual management, incorporating transplant, CART and multiple novel immune therapy approaches. Finally, we highlight the importance of meticulous vaccination schedule for patients with myeloma for all common viral, bacterial pathogens and vaccination against COVID-19.

José M. Larios
Ascension Providence Hospital, Department of Internal Medicine, Division of Hematology/Oncology. Southfield Michigan ; Michigan State University, Clinical Lecturer. East Lansing, Michigan.

Howard Terebelo
Ascension Providence Hospital, Department of Internal Medicine, Division of Hematology/Oncology. Southfield Michigan ; Michigan State University, Associate Professor. East Lansing, Michigan.

Abstract

Since the year 2000, we have seen unprecedented improvement in newly diagnosed multiple myeloma in terms of progression-free survival and a doubling of overall survival in 2009 from 2.5 years to 5 years. Patients treated now expect a median survival of 7.5 years, while those receiving quadruplet therapy, stem cell transplant, and consolidation and maintenance therapy have an expected survival up to 11 years.

Factors contributing to these improved outcomes include novel agents, antibodies, B-cell Maturation Agent-directed therapy, chimeric antigen receptor T-cells, bispecific antibodies, selective use of stem cell transplant, and supportive care measures such as bisphosphonates, prophylactic antimicrobials, cytokines, and intravenous immunoglobulins. Incorporation of these novel therapies in conjunction with increasing understanding of the genomic landscape of multiple myeloma and the evolving use of minimal residual disease negativity should persuade the oncology community to treat patients with high-risk smoldering multiple myeloma and guide treatment of early relapse in patients with newly diagnosed multiple myeloma. Here, we review early interventions within the context of genomic changes, minimal residual disease status, and strategies for treating high-risk smoldering multiple myeloma and standard and high-risk newly diagnosed multiple myeloma to improve progression-free survival, overall survival, and provide context for which patients may be considered cured.

Marta Domínguez-Bernaus
Department of Ophthalmology, University Hospital Arnau de Vilanova, Lleida, Spain

Pau Cid-Bertomeu
Department of Ophthalmology, University Hospital Arnau de Vilanova, Lleida, Spain

Felip Vilardell
Department of Pathology and Histology, University Hospital Arnau de Vilanova, Lleida, Spain.

Valentin Huerva
Department of Ophthalmology, University Hospital Arnau de Vilanova, Lleida, SpaiN; School of Medicine, University of Lleida, Lleida, Spain.

Abstract

Conjunctival plasmacytomas are rare tumours that may be solitary or related with multiple myeloma (MM), a malignant systemic plasma cell neoplasm that tends to metastasize. Plasma cell infiltration of bone marrow and presence of immunoglobulin is characteristic of MM. It may cause extraskeletal spread being the ocular tissue involvement very rare.

We report a case of a 57-year-old male patient affected of a caruncular mass that has increased of volume in the past two months. The patient was previously diagnosed of extramedullar affection of MM and he had no treatment in that moment. An excisional biopsy confirmed the diagnostic of a conjunctival plasmacytoma secondary to MM Immunoglobulin D (IgD). Second line systemic chemotherapy treatment produced total regression.

Ocular surface plasmacytoma is an uncommon entity that has to be suspected in a known myeloma patient with a conjunctival mass growth, including the caruncle. The presence of conjunctival plasmacytoma may be a sign of recurrence and insufficient chemotherapy as showed our case. Therefore, regular ophthalmological examinations should be done to the myeloma patients without any treatment.

Natalia Neparidze, MD
Yale University School of Medicine New Haven, CT

Krystal W. Lau, PhD
Flatiron Health, New York, NY

Xiaoliang Wang, PhD
Flatiron Health, New York, NY

Scott Huntington, MD, MPH
Yale University School of Medicine New Haven, CT

Omer Jamy, MD
University of Alabama at Birmingham, Birmingham, AL

Gregory S. Calip, PharmD, MPH, PhD
Flatiron Health, New York, NY

Harsh Shah, DO
University of Utah, Huntsman Cancer Center, Salt Lake City, UT

Deborah M. Stephens, DO
University of Utah, Huntsman Cancer Center, Salt Lake City, UT

Rebecca Miksad, MD, MPH
Flatiron Health, New York, NY

Ravi B. Parikh, MD, MPP
University of Pennsylvania, Philadelphia, PA

Samuel Takvorian, MD, MSHP
University of Pennsylvania, Philadelphia, PA

Gaurav Goyal, MD
University of Alabama at Birmingham, Birmingham, AL

Erlene Seymour, MD
Flatiron Health, New York, NY

Abstract

Background: The COVID-19 pandemic impacted healthcare visit trends, transitioning care to utilize telemedicine. We aimed to investigate if the uptake in telemedicine during pandemic was equitable across racial groups for patients with hematologic malignancies.

Methods: Using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database we analyzed patients with diagnosis of acute myelogenous leukemia (AML), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) or multiple myeloma (MM). Patients were categorized into treatment types within lines of therapy: outpatient (oral therapy and outpatient infusions combined with oral therapy) vs. inpatient treatments (chemotherapy, cellular therapy). Monthly visit rates were calculated as the number of visits (telemedicine or in-person [in-clinic treatment administration, vitals, and/or labs]) per active patient per 30-day standardized month. We used time-series forecasting methods on pre-pandemic monthly visit rate data (March 2016 – February 2020) to estimate projected counterfactual monthly visit rates between March 2020 – February 2021.Telemedicine uptake was descriptively analyzed over time (t).

Results: We included 18,924 active patients (2,394 Black and 16,530 White) and 884,504 visits (117,673 Black and 766,831 White). 4,053 AML, 3,468 diffuse large B cell lymphoma, 1,943 follicular lymphoma, 2,151 mantle cell lymphoma, 5,926 chronic lymphocytic leukemia and 7,752 myeloma patients. Black patients had no significant reductions in in-person visit rates throughout the pandemic period compared to the projected rates. Conversely, White patients experienced an 18% (95% PI 9.9% – 25%) lower rate of in-person visits for outpatient therapy during the early pandemic (March – May 2020) (actual monthly visit rate 1.61; projected visit rate 2.0 [95% CI 1.8-2.2]). Telemedicine uptake was significantly higher for White patients compared with Black patients for all diseases and treatment categories between March 2020-February 2021 (t = 9.5, p < 0.01), AML inpatient (t = 2.4, p = 0.04), MM outpatient (Figure 3C) (t = 6.0, p < 0.01) and MM inpatient treatment categories (Figure 3D) (t = 2.3, p = 0.04). 

Conclusions: White patients had significantly higher telemedicine uptake compared with Black patients for all treatment categories. These findings challenge healthcare systems to direct efforts toward reducing the gap in healthcare access.

Jan S. Moreb
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Amanda Edwards
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Savannah Perry
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

James Dugan
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Raymond Thertulien
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Kathleen Elliott
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Alan P Skarbnik
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Kimberly Ward
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, NC

Abhishek R. Chilkulwar
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Patricia L Kropf
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Franklin Chen
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Abstract

COVID 19 infection had significant impact, including high mortality rate, in immunosuppressed patients including patients with hematological malignancies undergoing hematopoietic stem cell transplantation. This retrospective study describes the characteristics and outcomes of COVID 19 infection in autologous stem cell transplantation (ASCT) recipients. The time period for the study was Feb 2020 to Feb 2022. During that time 29 patients (28%) out of 102 ASCT recipients became infected with COVID 19 diagnosed by PCR test. 22 and 7 were multiple myeloma (MM) and lymphoma (Ly) patients, respectively.  Infection rate was 30.5% among MM patients and 23% among Ly patients. Median age was 59 years, 16 were females, 45% were Caucasians. Eight patients had infection prior to first ASCT, and one prior to second ASCT. Nine developed the infection within 12 months post ASCT. 6 patients had 2nd episode of infection within 8-20 months from 1st episode, only one patient required hospitalization. One MM patient contracted the infection from his relatives while in the hospital undergoing ASCT. He was one of total of 3 deaths from COVID infection. All 3 patients had significant comorbidities including 2 on dialysis and the 3rd had chronic kidney failure stage 3B, all were MM patients within < 1 year from ASCT. Two of them were vaccinated with the primary shots but no boosters. Overall, 8 patients were hospitalized due to COVID infection, 7 had multiple comorbidities and 6 had low absolute lymphocyte counts (ALC). Sixteen patients were noted to have low ALC around the time of infection, 5 were Ly patients. Seven patients had no symptoms, only 3 of them were vaccinated. Overall, 12 were vaccinated at the time of infection. 10 patients received monoclonal antibodies after they became positive for COVID. Evusheld was given to 2 patients. Other treatments used mainly in hospitalized patients include dexamethasone, remdesivir, and fresh frozen plasma. In conclusion, our patient population seems to have done better than published reports with about 10% mortality from COVID infection. Comorbidities, especially advanced renal failure, and low ALC may have contributed to worse morbidity and mortality outcomes.