PURPOSE The globalization of clinical trials has accelerated recent advances in multiple myeloma (MM). However, it is unclear whether trial enrollment locations are reflective of the global burden of MM and whether access to novel therapies is timely and equitable for countries that participate in those trials. METHODS To assess this, we characterized where MM trials that led to US Food and Drug Administration (FDA) approvals were conducted and determined how often and quickly these drug regimens received approval in their participating trial countries on the basis of country income level and geographic region. RESULTS A systematic review was conducted to identify all MM clinical trials that met their primary endpoint, enrolled patients outside the United States, and resulted in FDA approval from 2005 to 2019. A total of 18 pivotal MM clinical trials were identified. High-income countries enrolled patients in 100% (18/18) of the trials identified, whereas upper-middle and lower-middle-income countries were represented in 61% (11/18) and 28% (5/18) of trials, respectively. No patients from low-income countries were enrolled. One trial enrolled patients in sub-Saharan Africa, and no trials enrolled patients in South Asia/Caribbean. For drugs/regimens that were approved in their participating countries, the median time from FDA approval to approval was 10.9 months. There were no drugs approved in lower-middle-income trial countries. MM trials leading to FDA approval are generally run in high-income, European, and Central Asian countries. CONCLUSION There are substantial disparities in where novel therapies are evaluated and where they are ultimately approved for use on the basis of income level and geography.

e20012 Background: Several US studies have evaluated ethnic differences in patients with multiple myeloma (MM), but few have focused on populations other than non-Hispanic Whites and Blacks. We examined ethnic differences in a contemporary cohort of MM patients and their presenting laboratory findings in a large, insured, community-based population, including findings across Asian American subgroups. Methods: Using the Kaiser Permanente Northern California (KPNC) Cancer Registry, we identified all new cases of MM from 2010-2018 and obtained data on age, sex, race/ethnicity, Asian subgroup, and presenting hemoglobin, calcium, and estimated renal function (eGFR derived from serum creatinine) from health plan databases. Moderate to severe anemia was defined by hemoglobin <10 g/dL, hypercalcemia by calcium >11 mg/dL, and chronic kidney disease (CKD) by eGFR: stage 3 (eGFR 30-59) and stages 4-5 (eGFR <30). MM incidence was estimated using membership denominators. Results: There were 2224 new MM cases (mean age 68y, 60% male) in 2010-2018, with an annual MM incidence of 7.9-9.8/100,000. Table 1 compares presentation by race/ethnicity. Non-Whites (45%) were more likely to present at age <65 than non-Hispanic Whites (30%, p<0.01). Black (43%) and Asian (39%) adults were more likely to present with hemoglobin <10 g/dL than non-Hispanic Whites (27%, p<0.01); Black adults were more likely to present with hemoglobin <10 g/dL than Hispanic adults (31%, p=0.02). Among the primary Asian subgroups, proportions with hemoglobin <10 g/dL were 38% (East Asian), 43% (Filipino), and 45% (South Asian). Blacks were more likely to present with CKD stage 4-5 (19.5%) than other races/ethnicities (p=0.04); differences between White vs non-White or Asian vs non-Asian were not significant. In Asians, 12.7% (South Asian) and 19.0% (Filipino, East Asian) presented with CKD 4-5. Asians were least likely to present with hypercalcemia (6.7%, p=0.03), and this was similar for Asian subgroups. Conclusions: We observed ethnic differences in MM presentation in a large integrated healthcare system. Blacks were more likely to have CKD stage 4-5 and hemoglobin <10 g/dL than non-Hispanic Whites. Asians were more likely to have CKD stage 4-5 than non-Hispanic Whites but least likely to have hypercalcemia. This is one of the first studies to identify Asian subgroups and examine variation across East Asians, Filipinos, and South Asians. Analyses examining ethnic differences in survival among MM patients are in progress.[Table: see text]

BACKGROUND: Osteoporosis is traditionally associated with post-menopausal women, but up to up to one-third of osteoporosis-related fractures occur in elderly men. The International Society for Clinical Densitometry (ISCD), the World Health Organization, and the Fracture Risk Assessment Tool (FRAX) all recommend using a white female reference for BMD T-score for men. However, in clinical practice and previous clinical trials, a sex-specific white male reference T-score is used. This report examines the implications of using a female versus male reference for T-score calculation in men. METHODS: We reviewed BMD findings in 703 men (age 70-85y) who experienced a proximal femur, humerus, or distal radius/ulna fracture. For this cohort, femoral neck BMD was used to calculate a BMD T-score using either the young adult male and young adult female peak values (mean BMD 0.930 ± 0.136 and 0.849 ± 0.111 g/cm2, respectively). Osteoporosis was defined by BMD T-score ≤ -2.5, and osteopenia by BMD T-score &lt; -1.0 and &gt; -2.5. We also calculated FRAX-estimated fracture risk for hypothetical men ages 60-85y, with and without prior fracture. We used the National Osteoporosis Foundation (NOF) recommendations for treatment based on BMD (osteoporosis by BMD, or osteopenia by BMD with a 10-year risk of hip fracture ≥ 3% or 10-year risk of major osteoporotic fracture ≥ 20%). RESULTS: The mean BMD for this cohort was 0.670 g/cm2 and the median T scores were -2.0 (male reference) and -1.7 (female reference). Using the male T-score, 29% of men were classified as having osteoporosis, while using the female T-score, only 21% were so classified. 36% of men age 70-79y and 19% of men age 80-85y with osteoporosis (using the male T-score) would be reclassified from osteoporosis to osteopenia when a female T-score is used. Hypothetical cases of men age 60-85y (height 170 cm, weight 70 kg, BMD 0.590 g/cm2 equivalent to a male T -2.5 or female T -2.2) were used to calculate 10-year hip fracture risk using FRAX. For these hypothetical cases, the calculated 10-year risk of hip fracture exceeded the NOF treatment threshold of 3% (10-year hip fracture risk) for all cases, with or without prior fracture. CONCLUSION: For elderly men with fracture with male-T osteoporosis and female-T osteopenia, the T-score reference population used does not alter treatment recommendations because the calculated hip fracture risk is already above the treatment threshold of 3%. This is also true for men age ≥70 without a prior fracture. Hence the debate pertaining to the appropriate T-score reference population for men has limited relevance for men age ≥ 70 years who are being screened for osteoporosis.

e20015 Background: Few studies have characterized patients with smoldering multiple myeloma (SMM) in ethnically diverse settings and data regarding progression to multiple myeloma (MM) in real-world clinical populations is limited. Using data from a large healthcare system, we examined a contemporary cohort of adults with confirmed SMM and their progression to MM. Methods: We conducted a retrospective cohort study of SMM cases from 2010-2017 in Kaiser Permanente Northern California (KPNC). We used the KPNC SEER-based Cancer Registry to identify potential SMM cases by ascertaining MM cases with either: 1) “asymptomatic, evolving, or smoldering myeloma” status in the Cancer Registry or 2) mention of “smoldering” in clinical records. Chart review was conducted for potential SMM cases and confirmed SMM status was assigned using the 2014 IMWG criteria. SMM cases were followed for progression to MM and myeloma-directed therapy, excluding those with KPNC membership <1 year after diagnosis. Time to MM progression (or treatment) was examined. SMM cases were classified during follow-up as: a) SMM, no progression to MM (and no receipt of myeloma-directed therapy); b) SMM, progression to MM (and receipt of myeloma-directed therapy); and c) SMM, receipt of myeloma-directed therapy without frank progression to MM (follow-up was censored at treatment). Results: During 2010-2017, we identified 152 adults with confirmed SMM. The median age at diagnosis was 71 years (IQR, 62-78), 56% were male, and 55% were non-Hispanic White, 17% Black, 9% Hispanic, and 18% Asian. During follow-up, 28% of patients progressed to MM, with a median time to progression of 1.2 years (IQR 0.8-2.0). Over half (58%) did not progress during a median follow-up time of 3.4 years, and an additional 14% received treatment before a MM-defining event. Progression data by demographic group is shown in Table. Conclusions: This is one of the first studies to examine SMM progression in an ethnically diverse cohort using the 2014 IMWG criteria. Although follow-up time was limited, we found that over half of the identified SMM cases did not progress to MM. However, patients who did progress to MM generally required treatment within 2 years of SMM diagnosis. These findings support efforts to identify high-risk patients with SMM who may benefit from early initiation of therapy. [Table: see text]

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