This retrospective observational study evaluated racial disparities among Black and White patients with multiple myeloma (MM). We included patients from a longitudinal de-identified EHR-derived database who had ≥2 visits recorded on or after 1/1/2011, documented treatment, and race listed as White or Black. Black patients (n = 1172) were more likely female (54.8%/42.9%) and younger (<65 years, 40.8%/30.8%) than White patients (n = 4637). Unadjusted median real-world overall survival (rwOS) indexed to first-line of therapy (LOT) was 64.6 months (95% CI: 57.8–74.0) for Blacks and 54.5 months (95% CI: 50.9–56.2) for Whites. Adjusted rwOS estimates (for sex, age at index date, and practice type) to either first- (aHR = 0.94; 95% CI: 0.84–1.06) or second-LOT (aHR = 0.90; 95% CI: 0.77–1.05) were similar. Unadjusted derived response rate (dRR) during first-LOT was 84.8% (95% CI: 80.7–88.1) for Blacks and 86.9% (95% CI: 85.0–88.5) for Whites (odds ratio [OR] = 0.78 [95% CI: 0.57–1.10]); in second-LOT, 67.2% (95% CI: 58.4–75.0) for Blacks and 72.4% (95% CI: 68.1–76.3) for Whites (OR = 0.72 [95% CI: 0.46–1.13]). High representation of Black patients enabled this robust analysis, albeit with limitations inherent to the observational data source, the retrospective design, and the analytic use of newly derived endpoints requiring further validation.
Bexarotene, a synthetic retinoid ligand for the retinoid X receptor (RXR), is a highly active agent in the treatment of relapsed or refractory CTCL with a response rate of ~45% (Arch Dermatol137: 581–93, 2001; J Clin Oncol19: 2456–71, 2001). Interferon alfa has a similar response rate although the doses and responses in the literature have varied. Promising results have been reported with combinations of retinoids and interferon alfa, including bexarotene (J Am Acad Dermatol50: 375–9, 2004). To explore this combination, a phase II trial was designed in which patients with CTCL were treated with bexarotene 300 mg/m2/day for at least 8 weeks. If less than a complete response was seen at this time, interferon alfa-2b at a dose of 3 million units escalated to 5 million units subcutaneously 3 times weekly was added for another 8 weeks. Responding patients could continue treatment beyond 16 weeks. Twenty-two patients with CTCL were enrolled in the trial: median age 58 years (22–79); 9 males, 13 females, TNM stages: IB (3), II (7), III (4), IV (8). One patient had no prior treatment; the rest had relapsed or refractory disease with a mean of 49 months from initial diagnosis to enrollment. Four patients had previously received bexarotene and 2 interferon alfa. Seventeen patients completed 16 weeks of treatment and are assessable for response, 1 has not completed 16 weeks and 4 received less than 16 weeks (1 early death, 1 non-compliant, 1 withdrawal of consent because of side effects, and 1 myocarditis, probably not treatment-related). Using reproducible objective criteria for response utilized in the single agent bexarotene trials cited above (Primary Endpoint Classification), 6 of 17 patients achieved a partial response and 1 a complete response (objective response rate 41%, 95% confidence intervals 18%–67%). Three of the 6 partial responses occurred with bexarotene alone at 8 weeks. Median duration of response was 2.7 months, range 1.1–7.6 months. Reversible grade 3 or 4 toxicities seen in more than 1 patient were hypercholesterolemia (2 pts.), hypertriglyceridemia (4 pts.), neutropenia (3 pts.), lymphopenia (2 pts.) and elevated AST in 2 patients. Lipid lowering agents were used in all patients. Six patients died, all of progressive disease from 1.6–29.9 months following initiation of treatment. The major response rate for the combination of bexarotene and interferon alfa is similar to that for bexarotene alone. Despite the wide confidence intervals that indicate that a small advantage might be missed by not increasing accrual, the clinical usefulness of this combination is limited by the inconvenience of interferon injections. Further trials in CTCL are planned combining bexarotene with other agents, including active cytotoxics.
Background International Myeloma Working Group (IMWG) consensus criteria for response in MM require reductions in both serum protein electrophoresis (SPEP) and 24-hour urine protein electrophoresis (UPEP) for patients without oligosecretory disease. Requiring both SPEP and UPEP results to assess response significantly limits evaluability in the real-world, given that 24-hour UPEP tests are not used often in routine clinical practice (Foster RB, et al. Blood. 2018;132(Suppl. 1):3536). We sought to determine if response events and response rates could be derived using data readily available in the EHR for patients with MM who received lenalidomide, bortezomib, and dexamethasone (RVD) therapy. Methods This retrospective cohort study used de-identified information from the nationwide Flatiron Health EHR-derived database; Institutional Review Board approval with a waiver of informed consent was obtained. The cohort included patients from oncology clinics across the U.S. with a confirmed MM diagnosis via chart review from 01/01/2011 to 06/30/2019. The cohort was limited to patients who received at least one line of therapy. Patients whose MM treatment start (captured through chart review) was > 30 days before start of activity in the database were excluded, as this may indicate missing therapy data. Patients were followed for response by either SPEP, UPEP, or serum free light chain (SFLC) lab tests. Patients were eligible if they had at least one measurable test (specimen type), consistent with IMWG criteria (SPEP ≥ 1 g/dL, 24-hour UPEP ≥ 200 mg, SFLC of any numeric value). Specimen type was determined using a hierarchy (SPEP > 24-hour UPEP > SFLC) when multiple test types were available. An initial baseline lab was assigned to each line of therapy: the highest lab value within 90 days of the start of the line of therapy, or the earliest lab within the line of therapy if there were only labs > 90 days after therapy start. Subsequent labs within the line were evaluated for a partial response (PR) or very good partial response or better (≥ VGPR) according to IMWG criteria based on percent change from baseline. Derived response rate (dRR) was defined as the proportion of patients who had at least one PR or better assessment during RVD therapy, among patients with a baseline lab value and a subsequent lab value during RVD ("assessable for response"). Results Out of 7,506 patients, 4,626 (61.6%) had at least one measurable SPEP test (n=4,257) or at least one measurable 24-hour UPEP test (n=788). Only 419 (9.1%) had at least one measurable test for both parameters. Patients who received first-line (1L) RVD and were assessable for response by SPEP or UPEP (n=1,379) had a dRR of 0.89. Among 1,196 patients with a response event tracked by SPEP during 1L RVD, only 102 (8.5%) had at least one of these events with a measurable 24-hour UPEP test conducted within 14 days. Those who received RVD in second-line and were assessable by SPEP or UPEP (n=222) had a dRR of 0.75. These response rates are generally consistent with results from the phase III SWOG S0777 trial investigating upfront RVD (overall response rate [ORR] 0.82) (Durie BGM, et al. Lancet. 2017;89(10068):519-527), and a phase II study of RVD in the relapsed/refractory setting (ORR 0.64) (Richardson PG, et al. Blood. 2014;123(10):1461-1469). Conclusions Strictly applying IMWG response criteria in routine practice settings may be challenging, as patients rarely have both SPEP and UPEP measured as part of routine clinical care. However, the results of this study suggest that response in real-world patients with MM can be effectively derived from the results of a single test type. Results from this single-specimen derivation are reasonably consistent with select published results across different lines of therapy. It should be noted that the real-world response rates reported are not confirmed by subsequent assessment and any formal comparison would have to account for differences in the patient characteristics between the real-world cohorts and those in clinical trials. Further studies may be warranted to investigate alternatives for defining CR in the real-world. Adherence to IMWG criteria in the real-world may be further limited by the requirement of a bone marrow biopsy for confirmation of complete response (CR), which may be performed less frequently than SPEP or UPEP lab tests. As such, discerning a VGPR from a CR may not be feasible with this real-world response approach. Disclosures Foster: Roche: Equity Ownership; Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Equity Ownership. Tromanhauser:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Equity Ownership; Roche: Equity Ownership. Gayer:Roche: Equity Ownership; Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Equity Ownership. Gonzales:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Equity Ownership; Roche: Equity Ownership. Maignan:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Equity Ownership; Roche: Equity Ownership. Opong:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding. Torres:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Equity Ownership; Roche: Equity Ownership. Carson:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding; Roche: Equity Ownership.
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