Citations

Abstract Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially the underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity as well and the issue should be addressed in conjunction with each other. Methods: Food and Drug Administration (FDA) drug approvals from 7/2007-6/2019 were reviewed to identify oncology approvals, and trials with age details were selected. The primary outcome was the weighted mean difference in age between the clinical trial population and realworld population for various cancers. The secondary outcomes were the prevalence of race reporting and association of age and race reporting with each other. Group comparisons for proportions were performed using the χ2 test while continuous variables were compared using multiple analysis of variance (MANOVA) test or students t-test as appropriate. P values < .05 were considered significant. Results: Of the 261 trials, the race was reported in 223 (85.4%) of the trials while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time – 29 (85.3%) in 2007-2010 vs. 49 (80.3%) in 2011-2014 vs. 145 (85.4%) during 2015-2019 (p-value=0.41). No significant association between type of cancer and race reporting was noted – 147 (86.5%) of solid cancer trials vs. 76 (83.5%) of hematological cancer trials reported race (p-value=0.52). Age discrepancy between the clinical trial population and the real-world population was present for several cancer types. The discrepancy was higher for studies that did not report race, mean difference - 8.8 years 4 (95% CI -12.6 to -5.0 years) vs. studies that did report the race, mean difference -5.1 years, (95% CI -6.4 to -3.7 years), p-value=0.04. Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations. In the meantime, reporting these characteristics for these crucial trials should be mandated. Citation Format: Thejus Jayakrishnan, Sonikpreet Aulakh, Mizba Baksh, Kianna Nguyen, Meghna Ailawadhi, Ayesha Samreen, Ricardo Parrondo, Taimur Sher, Vivek Roy, Rami Manochakian, Aneel Paulus, Asher Chanan-Khan, Sikander Ailawadhi. Disparity in race and age reporting in landmark cancer clinical trials: Underrepresentation of the traditionally underserved U.S. population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-104.

AbstractWaldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1 % of cases and can be differentiated from infectious etiologies based on fluid cytology.

Abstract Background: trALL is an important secondary primary malignancy (SPM) that has recently been appreciated. While patients (pts) with MM have an 8%-17% risk of developing an SPM while on lenalidomide (R) maintenance following autologous stem cell transplant (ASCT), trALL has been rarely observed. Little is known about the characteristics of trALL in pts with MM compared to pts who had other malignancies prior to the development of trALL. We define tALL as any prior exposure to cytotoxic chemotherapy and/or radiation for another malignancy, and herein, we report a comparative analysis of characteristics and outcomes of pts with trALL with and without MM from the Mayo Clinic Cancer Center (MCCC). Methods: We performed a systematic search in the 3-site MCCC registry and included all pts diagnosed and received at least 1 cycle of ALL-directed therapy and/or underwent allogeneic transplantation (AlloHCT) for ALL between 2007-2020. All cases of trALL in this series are B-ALL. Comparisons of characteristics between trALL patients with and without MM were made using a Wilcoxon rank sum test (continuous variables) or Fisher's exact test (categorical variables). Time-to-event variables were compared using unadjusted Cox proportional hazards regression models. Results: 70 trALL pts (14 MM [20%], 56 non-MM [80%]) were identified during the study period. The median age at trALL diagnosis was 63.9 (range 47-71) for MM pts and 63.1 (range 18.2-84) for non-MM pts. Median follow-up from trALL diagnosis was 1.42 years (range 0.02-10.6 years). The most common prior non-MM malignancies among tALL pts were breast (28.6%), lymphoma (17.9%), myeloid (17.9%), and GU/GYN (14.3%). Amongst the 14 MM pts, 100% (n=10) had ISS-I disease, 8 (57%) had IgG K MM, 1 (n=10) had high risk cytogenetics, 8 (57.1%) received R-based induction , 4 (28.6%) received CyBorD induction, 4(28.6%) received VRD induction, 3 (21.4%) received RD induction. 10 (71.4%) pts were actively on R when they developed trALL, 8 (57.1%) pts received prior ASCT. The median time to develop trALL following ASCT for MM was 46.3 months (m), (95% CI 20.4-67.6), 12 (85.7%) pts received R maintenance with a median duration of 53m (95% CI 16.9-121). The median time to develop trALL after initiation of R maintenance was 61.2m (95% CI 16.9-123.4). The most common trALL induction regimen received was HyperCVAD which was used in 71.4% of MM pts and 51.8% of non-MM pts. In comparison to non-MM pts, MM patients had a significantly lower WBC at diagnosis (Median: 2.0 vs. 5.8, P=0.005),no t(9;22) BCR/ABL1 cytogenetics (0.0% vs. 35.7%, P=0.008), a higher frequency of hypodiploid/near-triploid (Ho-Tri) cytogenetics (42.9% vs. 12.5%, P=0.009), and a lower frequency of prior radiation therapy (7.1% vs. 44.6%, P=0.012). MM pts had a higher frequency of AlloHCT for trALL (71.4% vs. 42.9%, P=0.075) and were more commonly in complete response (CR) at transplant (100.0% vs. 70.8%, P=0.078). No trALL in MM pts were Ph-like ALL. There was a statistically significant difference in time to development of trALL between previous malignancy locations (P=0.018), with GU/GYN (Median: 9 years) having the longest time and myeloid (Median: 3 years) having the shortest time; MM was 6 years. In the overall pt cohort, 56 (80%) pts achieved a complete response after induction and 60% (n=25) were minimal residual disease (MRD)+ after induction. Pts with MM had a significantly lower likelihood of being MRD+ after induction (OR=0.09, P=0.015). Overall, 24.3% of pts relapsed after induction therapy for trALL; 39 (55.5%) died after trALL diagnosis including 43% (n=35) who died after AlloHCT. Although pts with MM tended to have better outcomes compared to non-MM trALL pts in terms of overall survival after trALL diagnosis (Figure 1A), survival after AlloHCT (Figure 1B), relapse rate after trALL diagnosis and non-relapse mortality after AlloHCT, none of these findings were statistically significant in this small cohort (Figure 1C). Conclusion: trALL is a unique SPM that can occur in pts with MM. It is associated with Ho-Tri cytogenetics and is BCR/ABL1 negative. The majority of MM pts that developed trALL had undergone prior ASCT and were on R maintenance when they developed trALL. Despite being more likely to have adverse cytogenetics features, MM-associated trALL has similar survival compared to non-MM-associated trALL which speaks to the poor survival outcomes of this SPM. Further research on trALL in MM pts is merited. Figure 1 Figure 1. Disclosures Litzow: Amgen: Research Funding; Pluristem: Research Funding; AbbVie: Research Funding; Actinium: Research Funding; Astellas: Research Funding; Omeros: Other: Advisory Board; Jazz: Other: Advisory Board; Biosight: Other: Data monitoring committee. Bergsagel: Janssen: Consultancy. Fonseca: Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; Bayer: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; BMS: Consultancy; Mayo Clinic in Arizona: Current Employment; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; Novartis: Consultancy; Merck: Consultancy; Sanofi: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Murthy: CRISPR Therapeutics: Research Funding. Ailawadhi: GSK: Consultancy, Research Funding; Sanofi: Consultancy; Pharmacyclics: Consultancy, Research Funding; Takeda: Consultancy; Medimmune: Research Funding; Xencor: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cellectar: Research Funding; Beigene: Consultancy; BMS: Consultancy, Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy; Ascentage: Research Funding. Foran: actinium: Research Funding; taiho: Honoraria; bms: Honoraria; servier: Honoraria; pfizer: Honoraria; novartis: Honoraria; OncLive: Honoraria; abbvie: Research Funding; boehringer ingelheim: Research Funding; takeda: Research Funding; trillium: Research Funding; aptose: Research Funding; revolution medicine: Honoraria; syros: Honoraria; sanofi aventis: Honoraria; certara: Honoraria; gamida: Honoraria; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding.

Abstract Background: AHCT is a standard of care treatment for eligible patients (pts) with MM. Most consensus guidelines recommend that at the time of first AHCT, enough APBHC should be collected to perform two AHCT. However, recent studies have shown that with each decade after 1990, the use of cryopreserved APBHC for a salvage AHCT has declined and is now in the range of 4.6-15% in the decade between 2010-2018. The collection and storage of APBHC for two AHCT incurs additional costs and a prior single center cost analysis revealed that having had collected for just one AHCT in a cohort of 726 MM pts would have saved 3.8 million USD between 1993 and 2011. 1 Most centers that perform AHCT for MM pts continue to collect and store PBAHC for 2 AHCT. Herein we evaluate utilization trends and costs associated with cryopreserved APBHC in patients with MM. Methods: We retrospectively evaluated the clinicopathologic data from 440 patients with MM who underwent APBHC mobilization and collection at Mayo Clinic Florida between 2010 and 2019. The number of apheresis/collection sessions and APBHC product collection yields were determined for patients who were mobilized by any method. We estimated the costs involved in PBSC collection (apheresis) and cryopreservation storage based on our institution-specific charges as of May 2021. The cost of 1 session of APBHC collection/apheresis was $4,680 and the cost of 1 year of APBHC cryopreservation was $4,790 per patient. Statistical analysis was performed using JMP Pro 15 (SAS). Chi-square and Fischer exact tests were used to carry out univariate analysis for categorical variables and Wilcoxon rank sum/Kruskal Wallis for continuous variables. Results: Patient demographics are shown in Table 1. 440 pts underwent at least one collection session and 347 underwent at least 1 AHCT. The median number of mobilization sessions was 1 (95% CI 1.0-1.03), the median number of collection/apheresis sessions was 2.0 (95% CI 2.39-2.59), 84.3% (n=371) required ≥1 collection session. The median number of CD34 stem cells collected was 7.6 x10 6 (95% CI 7.76-8.19 x10 6), and the median number of infused CD34 cells was 4 x10 6(95% CI 4.13-4.37x10 6). The median cost of total collection sessions (defined as # of apheresis/collection sessions x $4,680) was $9,360 per pt (95% CI $11,181-$12,100). The median cost of cryopreservation (defined as # of years of storage x $4,790) was $19,160 per pt (95% CI $9,682-$22,252). The median number of years of storage was 4 (95% CI 4.11-4.65). 77(17.5%) pts have had APBHC in storage for <2 years, 218 (49.5%) have had APBHC in storage for 2-5 years, and 145 (33%) had have APBHC in storage for >5 years. The median time from MM diagnosis to AHCT was 9.0 months (range 13.8-18.5). 82% of patients collected enough APBHC (≥6x10 6, at least 3x10 6 per AHCT)for 2 AHCT. 8% of patients had all APBHC infused during their first AHCT, 83.5% had half of their APBHC infused during their first AHCT, and 8.1% had a different amount of APBHC infused during their first AHCT thus 91.6% of patients who collected APBHC had cells in storage. The median OS for the entire cohort after AHCT was 94.7 months (95% CI 88.6-100). Out of 347 patients who had stem cells in cryopreservation, 5 (1.4%) underwent a salvage AHCT and 3 (0.9%) underwent a tandem AHCT. 61% percent of patients had ≥1 excess collection sessions for APBHC that ultimately went unused. The median cost of excess collection sessions was $4,680 per pt (range, $4,680-$32,760) and the median total cost for excess collection sessions plus costs for storage was $23,840 per pt (range, $4,680-$85,450). The sum of costs of excess collection sessions was $2,077,920 and the sum of costs of cryopreservation was $5,812,665. Conclusion: The results of this single center analysis show that only 1.4% of patients underwent a salvage AHCT between 2010 and 2019 while 91.6% had APBHC left in storage which confirms the increase in storage of cryopreserved APBHC and declining trend in the use of stored APBHC for salvage AHCT in pts with MM. This is likely due to the advent of next generation novel therapies such as monoclonal antibodies, proteasome inhibitors and immunomodulatory agents. Excess collections, and cryopreservation of unused APBHC incur a cost of nearly $8 million. Institutional policies regarding universal APBHC collection and long-term storage should be reevaluated. 1Phipps C, et al. Bone Marrow Transplantation 2015:50;663-667. Figure 1 Figure 1. Disclosures Murthy: CRISPR Therapeutics: Research Funding. Ailawadhi: Sanofi: Consultancy; Medimmune: Research Funding; Genentech: Consultancy; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Xencor: Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy; Beigene: Consultancy; GSK: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy; Cellectar: Research Funding; Karyopharm: Consultancy.

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

SummaryWe report a comparative analysis of patients with therapy‐related acute lymphoblastic leukaemia (tr‐ALL) vs de novo ALL. We identified 331 patients with B‐ALL; 69 (21%) were classified as tr‐ALL. The most common prior malignancies were breast (23·2%) and plasma cell disorders (20·3%). Patients with tr‐ALL were older (median 63·2 vs. 46·2 years, P < 0.001), more often female (66·7% vs. 43·5%, P < 0·001), and more likely to have hypodiploid cytogenetics (18·8% vs. 5·0%, P < 0·001). In multivariable analysis, patients with tr‐ALL were less likely to achieve complete remission [odds ratio (OR) = 0·16, P < 0·001] and more likely to be minimal residual disease‐positive (OR = 4·86, P = 0·01) but had similar OS after diagnosis and allo‐haematopoietic cell transplantation.

Waldenström Macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL and management is poorly understood. We describe a case of an 81-year-old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Introduction: Daratumumab (D) is an anti-CD38 monoclonal antibody, used frequently in combination with immunomodulatory drugs (IMiDs), lenalidomide (Len) and pomalidomide (Pom). There are no studies comparing DRd to DPd in Len-exposed or refractory multiple myeloma (MM). We present the Mayo Clinic experience of DPd and DRd utilization and outcomes. Methods: We identified consecutive MM pts who received D, between 1/2015 and 4/2019 at Mayo Clinic. We included pts who were exposed (at least one full cycle, 21/28 days) or refractory (progression on full dose or maintenance Len during treatment or within 60 days of stopping Len) to Len prior to D and received 1 to 4 prior lines of therapy. Only Pts who received DRd and DPd were included. Results: Out of 411 evaluable pts 162 met the inclusion criteria; 67 were Len exposed, but not refractory and 95 were Len refractory. Pts' characteristics are shown in Table 1. DRd was used in 76 (47%) and DPd in 86 (53%) pts. Majority of pts (105; 65%) received DPd or DRd in the 2nd or 3rd line and 104 pts (64%) are still alive. In Len refractory pts, the median time from last dose of Len to D initiation was 1 mths (interquartile range 0-6.5). Seventy pts (43%) had high-risk cytogenetics (HR). Only 11 pts (7%) underwent autologous hematopoietic cell transplant after DPd or DRd regimen. There was no significant difference between pts who received DRd and DPd in terms of age (&gt;65 years), gender, race, proportion exposed or refractory to Bortezomib, number of prior lines of treatment (&gt;2), or HR status (p&gt;0.05 for all). Pts who received DPd were 4 times more likely to be Len refractory compared to pts who received DRd, p=0.0008. Median follow up time for the whole cohort from initial diagnosis was 92 mths (CI 95%; 79.5-107), while from D start date was 30 mths (CI 95%; 27-34). Median PFS for the whole cohort was 21 mths (CI 95%; 15-25) and median OS was 138 mths (CI 95%; 111-193). In Len exposed but not refractory pts, n=67, the overall response rate (ORR) was 82% in the DRd group compared to 68% in the DPd group, p=0.2. There was no difference in median PFS; 25.5 mths (CI 95%; 23-NR) for DRd compared to 25 mths (CI 95%; 5-NR) for DPd, p=0.37. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 138-NR) and 145.5 mths (CI 95%; 70-NR), respectively, p=0.06. In the 48 Len exposed but refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 39 mths (CI 95%; 23-NR) for DRd compared to 21 mths (CI 95%; 3-NR) for DPd, p=0.11. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; NR-NR) and 145.5 mths (CI 95%; 36-NR), respectively, p=0.13. In Len refractory pts only, n=95, the ORR was 84% in the DRd group compared to 58% in the DPd group, p=0.009. There was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 9 mths (CI 95%; 5-15) for DPd, p=0.18. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 78-NR) and 106 mths (CI 95%; 66-183), respectively, p=0.5. In the 57 Len refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 13 mths (CI 95%; 5-NR) for DPd, p=08. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 69-NR) and 105 mths (CI 95%; 47-NR), respectively, p=0.35. In the 16 Len exposed but not refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, the median PFS was better in the DRd group; 24.4 mths (CI 95%; 12-NR) compared to 3.3 mths (CI 95%; 1.9-27.5) for DPd, p=0.0093. However, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 51-NR) and NR mths (CI 95%; 18-NR), respectively, p=0.13. In the 29 Len refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, there was no statistically significant difference in median PFS; 18 mths (CI 95%; 6-43) for DRd compared to 6 mths (CI 95%; 4-13) for DPd, p=0.22.Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 47-NR) and 53 mths (CI 95%; 26-105), respectively, p=0.2. Conclusions: D+IMiD regimens after prior Len exposure/refractoriness are commonly used in real-world, despite the lack of data from prospective clinical trials. Combining D with IMiDs in Len exposed or refractory pts is efficacious, whether the IMiD is Len or Pom. Our study shows that regardless of prior Len use, DRd is at least equivalent to DPd. Prospective studies should be done to confirm these observations. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding. Fonseca:Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Dingli:Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding.