PURPOSE: Initial reports indicate that access to contemporary therapies currently used in North America for the treatment of multiple myeloma (MM) varies internationally. No studies have quantitatively reported the extent of disparities in the access to MM therapies worldwide, with a goal to investigate access to MM therapies and barriers globally. METHODS: From June 18 to July 15, 2023, an electronic survey was distributed to 176 oncologists treating MM outside the United States. MM drugs were categorized by accessibility, with the cutoff for adequate access set at 60% of respondents affirming easy/moderate access. RESULTS: Ninety-five (54%) respondents from 33 countries completed the survey. Fifty-one percent of the respondents were from university-based academic programs, and 17% of the responders treated only plasma cell disorders. Most respondents had adequate access to noncellular MM therapies, except for isatuximab, ixazomib, selinexor, and elotuzumab. Among the cellular therapies, 17% had access to Chimeric Antigen Receptor T-cell therapy, whereas 23% had access to approved T-cell engagers (TCEs). Financial stress on patients and health care systems has emerged as a primary barrier to global inaccessibility of treatment drugs. CONCLUSION: Global access to novel MM therapies remains challenging, and we have identified barriers and suggested strategies to bridge this gap.

Background: Despite recent advances in the treatment of multiple myeloma (MM), the disease remains incurable. Agents targeting the programmed death-1 (PD-1) axis have become key treatments for many cancers; however, monotherapies with PD-1/PD-L-1 inhibitors (PD-1i) have shown a limited efficacy in MM patients. We conducted a meta-analysis to evaluate the safety and efficacy of PD-1i in combination with standard of care (SOC) therapies for MM. Methods: A systematic search identified phase II and III randomized clinical trials involving MM patients treated with PD-1i, using terms such as “Relapsed Multiple Myeloma” and “PD-1 inhibitors.” The search included trials published in English after 2016 using the PubMed, CINAHL, and Cochrane databases. Data were analyzed using RStudio v4.4.2, with survival data assessed using Kaplan–Meier methods and Cox proportional hazards analysis. Results: Our search yielded 19 total trials, of which 5 (representing 889 unique patients) met the criteria for inclusion. A total of 488 patients received PD-1i + SOC, and 401 received SOC alone. The median progression-free survival (PFS) was 6.26 months for the PD-1i + SOC group and 7.34 months for the SOC alone group (HR, 1.2; 95% CI: 0.95–1.41; p = 0.14). The median overall survival (OS) was 22.49 months for PD-1i + SOC compared to 24.38 months for SOC alone (HR, 1.11; 95% CI: 0.87–1.42, p = 0.36). The PD-1i group showed a higher incidence of all-grade pneumonia (RR = 1.44, 95% CI: 1.03–2.02, p = 0.03), grade ≥ 3 neutropenia (RR = 1.36, 95% CI: 1.00–1.85, p = 0.05), immune-mediated adverse events (RR = 10.1, 95% CI: 0.38–271.1, p = 0.17), and grade ≥ 3 irAEs (RR = 9.59, 95% CI: 0.62–148.8, p = 0.11). Conclusion: This analysis highlights the limited efficacy and increased toxicity of adding PD-1i to SOC in MM patients. Further research is needed to explore whether targeting the PD-1/PD-L1 axis in combination with novel therapies can safely enhance the therapeutic efficacy in MM patients.

Background: Primary plasma cell leukemia (pPCL) represents the most aggressive plasma cell dyscrasia with a poor prognosis and survival of <3 years. The International Myeloma Working Group (IMWG) adopted more inclusive diagnostic criteria for pPCL in 2021, including patients with 5% or more circulating plasma cells (down from 20%). Most published studies of pPCL do not include patients who meet the criteria for pPCL based on the newer diagnostic guidelines, and the data on the optimal treatment of pPCL is scarce. In our multi-center retrospective analysis, we report data on treatment regimens used in 67 pPCL patients to characterize outcomes in this population. Methods: We included patients with newly diagnosed pPCL between 2010 and 2023 based on the 2021 IMWG definition at one of three academic centers. Results: Our results suggest significant improvement in overall response rate (ORR) and progression-free survival (PFS) with the use of autologous stem cell transplant, but without additional benefit for a tandem transplant. The presence of high-risk cytogenetics was an independent risk factor for progression in the cohort. Conclusions: Our dataset represents one of the largest cohorts to date using the expanded definition of pPCL adopted by the IMWG in 2021 and stresses the importance of taking pPCL patients to transplant. Unfortunately, our study was not powered to determine the efficacy of individual induction and maintenance regimens, and many patients diagnosed with pPCL are ineligible for transplant based on end-organ damage at diagnosis or from disease that is refractory to induction therapy, underscoring the need for early diagnosis and treatment in hopes of preserving transplant eligibility.

Healing after transmetatarsal amputation (TMA) depends on adequate tissue perfusion. Revascularization prior to minor amputation improves amputation-free survival, limb preservation, and wound healing in patients with ischemic wounds. However, the optimal interval between revascularization and amputation remains unclear. The TriNetX real-world clinical data platform was used to identify patients with chronic limb-threatening ischemia (CLTI) who underwent endovascular revascularization followed by TMA. Patients were categorized into early TMA (≤7 days after revascularization) and late TMA (8-30 days). Propensity score matching was performed using demographics, comorbidities, laboratory values, and concurrent therapies. Major amputation and all-cause mortality at 6 months and 1 year were evaluated using Cox proportional hazards models. Kaplan-Meier curves and log-rank tests were used for time-to-event analyses. Among 700 patients with CLTI treated with revascularization before TMA, 508 underwent early TMA and 192 underwent late TMA. After matching, 185 patients remained in each group (96.3% match rate). The mean age was 66.9 ± 10.9 years, 78.1% were male, and mean follow-up was 237.2 days. At 6 months, major amputation (hazard ratio [HR], 0.87; 95% CI, 0.51-1.46; P =.597) and all-cause mortality (HR, 0.74; 95% CI, 0.45-1.20; P = .220) did not differ between groups. At 1-year, major amputation (HR, 0.87; 95% CI, 0.52-1.45; P = .599) and mortality (HR, 0.73; 95% CI, 0.46-1.14; P = .164) also remained similar. A composite endpoint of major amputation or all-cause mortality was also similar between groups (HR, 0.995; 95% CI, 0.694-1.425; P = .978). Among patients with CLTI undergoing endovascular therapy and subsequent TMA, early (≤7 days) vs late (8-30 days) amputation timing did not significantly affect major amputation or survival outcomes.