Purpose of Review
Given the median age at diagnosis of 69, multiple myeloma (MM) is commonly identified among elderly individuals. Over-treatment of the frail may lead to unnecessary morbidity, while ...under-treatment of fit elderly patients may prevent improvement in organ function; both instances reducing quality of life. Here, we summarize assessments of frailty and include considerations in managing newly diagnosed elderly MM patients.
Recent Findings
Eligibility criteria for studies of anti-myeloma agents have traditionally relied on performance status and comorbidities; however, geriatric and myeloma-specific frailty assessments are beginning to be incorporated for more accurate stratification of patients for treatment. The IMWG and R-MCI scores are validated metrics that predict survival in elderly MM patients. In addition, dose-attenuated induction regimens and conditioning before autologous transplant may decrease morbidity in elderly MM patients.
Summary
Although MM remains incurable, multi-drug regimens have the ability to prolong survival of both untreated and relapsed elderly patients. Older patients require a highly individualized approach since they may have preexisting organ dysfunction, worse frailty scores, and variable goals of care.
Introduction: Multiple Myeloma (MM) presents at a median age of 69. Patients age 50 or younger represent only 10% of diagnoses and are less well-characterized. Some studies have suggested that ...younger MM patients are more likely to present with lytic lesions, be IgD subtype, have high-risk cytogenetics, and have relatively improved survival. We aimed to characterize this understudied population in the modern era. Methods: We conducted a retrospective chart review of patients age <50 meeting IMWG criteria for symptomatic MM treated across our institution's cancer center network between 2010 and 2023. Overall survival was defined as time in months from diagnosis to last follow-up or death. Time to relapse after transplant was captured. Results: We identified 97 younger MM patients, with a median age of 44 (range 26-50). Males and females represented 50.5% and 49.5% of cases respectively. Complete demographics are listed in the table. The most common MM subtype was IgG Kappa (40%), and 23% had light chain-only disease. Incidentally found cases, defined as abnormalities on imaging or labs ordered for another reason, represented 11% of cases. 61% of patients presented with a skeletal issue such as bone pain and/or pathologic fracture. Presenting features are described in the table. At time of diagnosis, 77% of patients were found to have lytic lesions. Few patients had previously identified MGUS (3%) or smoldering MM (5%). Regarding cytogenetics, 18% had one or more high-risk features. The most common frontline treatment was VRD. As shown in the table, 66% and 29% received 3 and 4 drug induction regimens respectively. Of note, 91% were referred for autologous stem cell transplant (ASCT), and 72% proceeded. 4 patients were deceased at the time of analysis. Survival for the entire population was 95.9% at a median follow up time of 65.5 months. In the patients who underwent ASCT, 41.2% relapsed with median progression-free survival of 57 (44-71) months. Conclusions: MM patients age <50 were found to be distinct from the known characteristics of the general population in several notable ways. There was equipoise among demographic features, with a nearly equivalent prevalence in males and females, and similar median ages across racial groups. We found a greater enrichment of light chain disease than expected, but less renal dysfunction at presentation. IgD subtype does not appear increased in this population. Younger patients do not appear more likely to have high risk cytogenetics. Lastly, survival for younger patients was higher compared to the reported 5-year survival of MM, which may be explained by the finding that these patients were treated primarily with triplet or quadruplet anti-myeloma regimens and often proceeded to ASCT.
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Background: Most ambulatory oncology practices utilize an on-call service that is essential for continuity of cancer care after office hours, yet there is limited literature about ...the dynamics of this care delivery model and how to improve it from a quality standpoint. We hypothesize that patients with more advanced cancers are more likely to require the on-call service due to acute symptoms arising during their treatment, and that this information can be used to create a risk model to predict subsequent hospitalization. Methods: We performed a single-center, retrospective review of sequential overnight and weekend calls received by an oncology practice with 16 physicians over a 20-week period from January-May 2020. Calls were classified as being either urgent, requiring immediate attention, or non-urgent, which could be addressed during office hours. Data were summarized using descriptive statistics, continuous and categorical variables were compared using Wilcoxon rank-sum test and Fisher’s exact test, respectively. Multivariate analyses were estimated by logistic regression using the penalized maximum likelihood estimation method. Results: The data set included 236 consecutive calls among 176 patients, with 65% females and median age of 68 (range: 25-87). Of these, 185 calls (78.4%) were deemed urgent, among which 139 (75%) were symptom-related. Among the 202 calls (85%) from patients with cancer, 164 (81%) of them were urgent, mostly due to symptoms (82%). Of these urgent calls, 44 (27%) resulted in admission within 24 hours (P < 0.0001), primarily related to treatment toxicity or disease progression (81%). Patients with stage 4 cancers (42%) or hematologic malignancies (28%) were more likely to use the on-call service. There was no significant difference between call urgency and treatment regimen (P = 0.06). In a multivariable model, advanced age OR = 1.03(1.0-1.07) and urgent calls OR = 33.1(2.7-401.0) were independently associated with risk of hospitalization. Of note, there were no differences in admissions before or after the peak of the COVID-19 pandemic in New York City (P = 0.49). Conclusions: We identified an association between after-hours calls and more advanced malignancy, which was independent of treatment regimen. The majority of on-call issues were urgent and symptom-related, with advanced age and urgent calls being most likely to result in hospital admission. These results suggest that strategies can be developed to prevent hospitalizations in patients at higher-risk for adverse events based on a multivariable risk model.
Survival in multiple myeloma (MM) has improved due to the ongoing revolution of therapeutic approaches. Nevertheless, many patients relapse, and additional novel approaches are required to prolong ...remissions and prevent disease progression.
Considering the success of monoclonal antibodies (mAbs) against CD38 and SLAMF7 in relapsed/refractory MM (R/R MM), additional antigens expressed on malignant plasma cells are being investigated as treatment targets. Among these, many trials are focusing on B cell maturation antigen (BCMA), using either antibody-drug conjugates (ADCs), bispecific T cell engagers (TCE), or chimeric antigen receptor T cells (CAR-T). Other potential targets include the myeloma markers CD138, GPRC5D, FcRH5, the plasma cell differentiating factors APRIL, TACI and BAFF, and the immune checkpoint proteins CD47 and TIGIT. Additionally, novel immunomodulatory Cereblon E3 Ligase Modulators (CELMoDs) offer the potential to overcome resistance to conventional immunomodulatory agents. Based upon PubMed and abstract searches primarily from the past 4 years, here we review the data supporting novel immunotherapies for R/R MM.
Overcoming disease resistance remains a challenge in R/R MM. Novel therapeutic approaches targeting MM antigens and/or enhancing immune cell function offer the potential to prolong survival and are actively being investigated in clinical trials.
Background: Superficial vein thrombosis (SVT) has been historically considered to have a low risk of distal embolization and mortality, typically not warranting anticoagulation in the absence of ...underlying risk factors for thrombosis. However, recent studies of outcomes of SVT in patients without malignancy revealed significantly increased incidence of deep venous involvement at the time of presentation, as well as higher than expected rates of complications, reported in up to 10% of patients (Decousus et al. Ann Int Med(152)2010:218-224). However, outcomes of SVT in patients with cancer have not been well studied, despite the known increased risk of malignancy-associated thrombosis. In this study, we examined the rate of complications in patients who developed SVT in the setting of active malignancy.
Methods: A retrospective single-center chart review of electronic medical records along with a corresponding database of radiology reports from NYU Winthrop Hospital from 2013 to 2019 was performed to identify patients with cancer who also had image-confirmed SVT. Patients were included if they had a synchronous or subsequent deep vein thrombosis (DVT) or pulmonary embolism (PE) during treatment, but excluded if they had a history of thrombosis prior to their cancer diagnosis, primary hypercoagulable disorder, or on therapeutic anticoagulation at the time of SVT diagnosis. Descriptive statistics for the overall sample, as well as a subgroup of subjects who were not treated at SVT diagnosis, were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).
Results: 490 patients were noted to have a diagnosis of SVT and cancer, and of these, 40 met the enrollment criteria. Demographic data are shown in the table below. Among the 40, 21 patients had upper extremity, and 19 had lower extremity SVT. As shown in the table, 15 patients (37.5%) had a concurrent thromboembolism at the time of SVT diagnosis. An intervention was provided in 26 (69% full dose and 11% prophylactic dose anticoagulation, 15.3% antiplatelet therapy, and 3.8% vena cava filter placement). Of these 26 patients, one who received prophylactic anticoagulation developed a subsequent DVT. This patient had stage IV colon cancer and recent surgical resection, and developed SVT associated with intravenous access. Among the 14 patients with SVT who were not treated, 6 (43%) developed subsequent complications including one with DVT at the same extremity, 2 with DVT at a different location, and 3 with recurrence of the underlying SVT. Five of these were stage IV gastrointestinal cancers (including 3 patients with pancreatic cancer, 1 with gastric, and 1 with cholangiocarcinoma), and one had stage IV ovarian cancer. Considering the 8 patients who were not treated and did not develop complications, there was no dominant cancer type (3 were stage IV breast cancer, 1 had stage I pancreatic cancer, 1 had stage III hepatocellular carcinoma, and one had chronic lymphocytic leukemia).
Conclusions: This study reveals a greater degree of concurrent SVT complications in the setting of malignancy compared to prior reports in patients without cancer. The rate of complications were higher in those patients who did not receive treatment (either prophylactic or therapeutic) for their SVT or who had metastatic disease. Although the overall incidence of SVT in cancer patients is low, data presented here suggest a higher than expected rate of complications within a 3 month span following SVT diagnosis in the setting of malignancy compared to prior reports of patients without malignancy. Prospective studies are needed to assess the benefit of anticoagulation in decreasing the risk for SVT complications in patient with active cancer.
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Braunstein:Celgene: Consultancy, Other: Advisory boards; Takeda: Consultancy, Other: Advisory Board; Amgen: Consultancy, Other: Advisory Board; AstraZeneca: Consultancy, Other: Advisory Board; Janssen: Consultancy, Other: Advisory Board, Research Funding; Verastem: Consultancy, Other: Advisory Board.
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Background: Studies on cancer patients during the COVID-19 pandemic have shown a decrease in new diagnoses, delays in care, and a shift to later stage disease presentations. Considering that ...NY has been an epicenter for COVID-19 in the U.S., we investigated its impact on new cancer diagnoses at the two campuses of NYU’s Perlmutter Cancer Center and hypothesized that there would be a decrease in presentations during the peak outbreaks in NY. Methods: We conducted a single center, retrospective analysis of new cancer diagnoses before, during, and after the peak of the pandemic between Dec 1, 2019, and Aug 31, 2020. Following IRB approval, subjects were identified using our cancer center database, which includes both inpatient and outpatient visits. Subjects were included regardless of their treatment plan. New diagnoses before COVID-19 (Dec to Feb), at first peak (March to May), and during the initial recovery phase (June-Aug) were assessed. No COVID-19 vaccines were available during this time. Results: As summarized in Table, during the initial COVID-19 peak, there was a substantial decrease in new patient visits with statistically significant differences seen by age and certain cancer types including breast, skin, and hematologic malignancies. In all cancers, there was a decrease in the proportion of new patient visits among those over age 75 during the peak. When confining analyses to breast, skin, and hematologic cancers, we saw a significant increase in the proportion of younger new patients at the peak period. We also observed an association between age and stage, with an increase in new stage I diagnoses in the younger (age 18-54) population at peak. Telemedicine was most utilized by the younger population during both peak and recovery periods. Conclusions: In this retrospective analysis, we found that during the initial COVID-19 peak, prior to vaccine availability, outpatient visits for hematologic and solid malignancies decreased at our cancer center in NY. The decrease in the proportion of all cancer types in elderly patients during the peak was likely related to hesitancy among this vulnerable population to seek care. The widespread use of telemedicine also likely contributed to the increased incidence in new patient visits in younger patients. Lessons learned from this experience can help guide outreach to vulnerable populations during future outbreaks, particularly by fostering telemedicine use among the elderly.Table: see text
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Background: Targeting CD38 in multiple myeloma (MM) using daratumumab-based regimens can prolong remission in both the newly diagnosed and relapsed settings. However clinical trials have ...excluded patients with creatinine clearances (CrCl) <30 mL/min, warranting real-world analysis of daratumumab use in MM patients with renal insufficiency. Methods: Following IRB approval, we performed a retrospective chart review of relapsed MM patients at our institution who had reduced CrCl and received at least one dose of either daratumumab between October 2018 and January 2022. All subjects received IV daratumumab, 52% went on to receive SQ. Outcomes included change in CrCl during treatment, adverse events, and survival. Survival was estimated using product-limit estimates. CrCl groups at daratumumab initiation of more or less than 30 were compared using the chi-square test or Fisher’s exact test, as deemed appropriate, for categorical variables and the two-sample t-test or Mann-Whitney test for continuous data (SAS Institute Inc., Cary, NC). Results: 101 MM patients were included, with median age of 74 (54-92); 46 (45.5%) were female. 14% were on hemodialysis. Patients had a median of 2 prior lines of therapy. Distribution of R-ISS stages were I (20%), II (35%), and III (45%). High-risk cytogenetics were present in 20%. A median of 23 daratumumab infusions (1-60) were delivered over a median of 18 months (median IV=16, SQ=10). Daratumumab regimens included DRD (32%), DPD (35%), DKD (13%), and DVD (35%). Median CrCl at MM diagnosis and at daratumumab initiation was 45 (7.3-101) and 40 (5.3-107), respectively, with 33% having CrCl <30. Following 3, 6, and 12 months (n = 95, 89, 69) on daratumumab-based regimens, median CrCl were 45, 43, and 41, respectively. There were no differences in renal function in patients who went on to receive SQ daratumumab. 16 patients had died at the time of data collection, and the median survival was 63 months. Of the 101 patients, 16 subjects were deceased at the time of data collection, and 23% of subjects had gone on to subsequent treatments. Analysis showed that there was a progression-free survival of 54% at 5 years. The most common adverse events reported were anemia (37%) and neutropenia (15%). Infusion-related reactions were reported in 19% of patients. Conclusions: This is the largest real-world assessment of outcome for MM patients treated with daratumumab-containing regimens in the setting of renal insufficiency. There was no significant impact of the treatment on renal function at 12 months. Compared to published data on patients treated with CrCl>30, there does not appear to be a detriment to survival or an increase in adverse events when using daratumumab regimens in patients with more advanced renal insufficiency.
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Background: Admission to a physical rehabilitation facility (RF) can improve mobility and quality of life metrics in cancer patients, however, limited data exist on how these ...admissions impact cancer-related outcomes. We hypothesized that admissions to a RF following hospitalization delays cancer-directed treatment and increases mortality compared to those who are discharged home. Methods: A retrospective chart review identified oncology patients who were being treated with either intravenous or subcutaneous cancer-directed therapy between 2010-2020 and admitted to either a RF or home following hospitalization. Exclusion criteria were patients not on active cancer-directed treatment or going to hospice. Comparisons of RF vs. home were made using a chi-square test or Fisher’s exact test for categorical outcomes. Median days to next chemotherapy for each group were assessed with Kaplan-Meier/Product-Limit Estimates with a corresponding 95% confidence interval. Results: Of 189 patients, 24 were admitted to a RF and 165 went home. The median age of the study population was 65.6 years, with more males (66.7%) admitted to a RF vs. discharged home (49.7%), and both groups having >50% advanced stage cancer; primarily GI malignancies (25.9%) (Table). There was a statistically significant increase in the percent of patients who experienced delays in the time to their next anticipated chemotherapy date in the RF group vs. home (70.8% vs. 30.3%, P<0.0001), as well as median days to next chemotherapy (38.5 vs. 22, P<0.007). 30-day readmission rates were higher in patients at a RF vs. home (50% vs 29%, P<0.04). There were no significant differences in mortality comparing RF vs. home at 3, 6, or 12 months from the index inpatient hospitalization. Conclusions: Hospitalized oncology patients who were admitted to a RF had significant delays in cancer-directed therapy. Despite the smaller sample size of patients in a RF, their 30-day readmission rates were higher, suggesting a need to carefully select patients who can afford delays in cancer treatment.Table: see text
Introduction:
In multiple myeloma (MM), chromosomal abnormalities (CAs) are valuable in risk stratifying patients and predicting disease free survival. While immunoglobulin isotypes have historically ...contributed to MM staging, more recently established classifications of CAs have allowed for a revised staging system that better predicts disease behavior. In this retrospective study, we hypothesized that CAs correlate with disease characteristics including immunoglobulin heavy chain isotype, degree of bone marrow infiltration (PC%), and end-organ damage.
Methods:
MM patients diagnosed between 2013 to 2019 were included in this retrospective chart review using electronic records from two distinct sources: (1) 442 patients from an independent pathology database and (2) a validation cohort composed of 110 patients from our institution. CAs were stratified by Mayo mSMART 2.0 criteria into standard, intermediate, and high-risk groups (Mikhael et al. Mayo Clin Proc 2013). End-organ damage was defined as the presence of lytic bone lesions, anemia, hypercalcemia, or renal failure on clinical presentation. Within each cohort, associations between categorical variables were made using the chi-squared test or Fisher’s exact test, as deemed appropriate. The Mann-Whitney test was used to compare between groups for continuous variables. A result was considered statistically significant at the p<0.05 level of significance. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).
Results:
552 MM patients were included in the study. Multi-variate analysis revealed that del(13q14), dup(1q21), t(4;14), trisomy (11q13), del(16q23), and hypodiploidy were associated with a significantly higher PC%, whereas kappa light chain only (LCO) disease was associated with a lower PC%. Higher median PC% was found when comparing the intermediate to standard CA risk group. IgA isotype was associated with intermediate risk CAs including del(13q) and standard risk CAs including t(11;14), while IgG isotype was associated with dup(1q21), and kappa LCO disease correlated with a higher rate of higher risk CAs including deletion of p53 at 17p13 and dup(1q21). With regard to clinical presentation, lytic lesions were more frequent in patients with normal cytogenetics and trisomy 11 and less frequent in IgA isotype, whereas the presence of anemia on presentation correlated with IgA isotype. Renal failure was associated with MAF translocations including t(14;16), a high-risk CA.
Conclusions:
We demonstrate that a relationship exists between specific CAs, immunoglobulin isotypes, and clinical presentations in MM. Our data indicate that IgA isotype is significantly associated with intermediate-risk cytogenetics including del(13q) and anemia on presentation, and that light chain disease and renal failure correlate with high risk CAs including del(17p13). These associations between biological and clinical features further support the concept of divergent cytogenetic evolution in MM as being an underlying factor leading to distinctive disease presentations.
Braunstein:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.
Introduction: Supportive oncology provided by palliative care consultation has proven to prolong survival in randomized studies of patients with advanced cancers, particularly in those with solid ...tumors. However, the impact of palliative care consultation is less well characterized in patients with hematologic malignancies. We hypothesize that patients with hematologic malignancies are less likely to receive inpatient palliative care consultation. In this study, outcomes of patients with hematologic malignancies who received inpatient palliative care consultation were compared to a control group of disease-matched controls who were not seen by palliative care.
Methods: A retrospective chart review of patients with hematologic malignancies admitted to our inpatient oncology service between 2013-2019 was performed. Data were summarized in SAS v9.4 (SAS, Cary, NC) using descriptive statistics for patients who received palliative care consultation and controls who did not, and these groups were also compared using Wilcoxon rank-sum, chi-square, and Fisher's exact tests as appropriate based on the type and distribution of the data. Multiple logistic regression models with stepwise variable selection methods were used to find predictors of outcomes.
Results: Over the 7-year study period, there were 3,654 admissions to the oncology service, among which 370 hematologic malignancy patients who were actively on treatment were included. Of these, 102 (27%) received palliative care consultation, and the 268 who were not seen by palliative care served as a comparator group. Demographics, disease subgroups, and outcomes are summarized in the table. Groups were similar in terms of comorbidities, as shown in the table. Palliative care consults were greater for patients with acute leukemia and myelodysplasia (38% in each group), and least for those with chronic leukemias (15%) and myeloproliferative diseases (18%). Median length of stay was longer for patients seen by palliative care (11.5 vs. 6 days, P=.001), and these patients were more likely to be admitted to the intensive care (27.5 vs. 8.6%, P<.0001). Readmissions within 30 days of discharge were significantly lower among patients receiving palliative care consultation (15.7 vs 26.9%, P=.024), and 6-month morality was higher (66.7 vs 14.6%, P<.0001). Among all the patients who died within 6-months of admission, 36% did not receive palliative care consultation.
Discussion: Patients with hematologic malignancies who received palliative care consultation had a lower 30-day readmission rate and higher 6-month mortality, despite lack of differences in the time from their cancer diagnosis compared to the control group not seen by palliative care. More than two thirds of all patients did not receive a palliative care consultation, nor did over a third of patients who expired within 6 months of admission. Further research is required to investigate other factors that might warranted palliative care consultation, such as the severity of illness at the time of hospitalization. Results of this study suggest that inpatient palliative care consultation is associated with decreased readmission rate, yet these services are underutilized in patients with hematologic malignancies who are projected to have shorter overall survival.
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Braunstein:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees.
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