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SummaryIbrutinib‐related data in Waldenström macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n = 67 (84%), treatment‐naïve, n = 13 (16%)] with WM, evaluated consecutively at Mayo Clinic, who received ibrutinib off‐study after its approval in 2015 for WM. Overall response rate (ORR) was 91%; major‐response rate (MRR) was 78%. The median time to first response and best response was 2·9 [95% confidence interval (CI): 2–4] and 5·7 (95% CI: 4–12) months, respectively. The median follow‐up was 19 (95% CI: 14–21) months; 18‐month progression‐free survival (PFS) was 82%. The median time on therapy was 12·5 (95% CI: 9·3–16·7) months, and the median duration‐of‐response was 32 (range: 23–32) months. Twenty‐five patients (31%) had discontinued therapy at last follow‐up (68% due to treatment‐related toxicities) and 18% of patients required dose reduction. Fatigue (12%) and atrial‐fibrillation (11%) were common non‐haematological toxicities. IgM rebound occurred in 36% of patients who abruptly discontinued ibrutinib. Following ibrutinib discontinuation, 84% of patients received subsequent treatment, achieving an ORR of 57% and MRR of 50%. The median PFS from commencement of subsequent salvage therapy was 18 months. Ibrutinib therapy, outside of clinical trials, is effective in WM, but is associated with toxicities and challenges, including IgM rebound and a high drug discontinuation rate for reasons other than disease progression.

Abstract Background A better understanding of social determinants of health and psychosocial and economic sequelae of cancer for an ethnoculturally diverse population is needed. A Patient-Reported Outcomes Quality of Life (PROQOL) instrument has been developed to capture less commonly discussed patient concerns. We sought to adapt this instrument and pilot it in underserved, ethnic minority cancer patients at Maricopa Integrated Health System (MIHS) in Phoenix, AZ. Methods Two focus groups (FG) were conducted to understand patient perspectives of an adapted Spanish version of PROQOL. A revised version based on FG data was then piloted among patients on active cancer treatment. Patients also completed a Linear Analog Scale Assessment (from 1-10) for quality of life (QOL) and its domains. Results All participants in both FG (11/12 female) were Hispanic, with a median age of 53 years. Participants agreed that the domains covered in the PROQOL represented the most important psychosocial needs in their cancer continuum. No difficulty in understanding the individual domains or questions for delving deeper into each domain was noted. Median age of 34 pilot study participants (74% female, 79% Hispanic) was 48 years. 28/34 completed the Spanish version. The most common concerns were ‘Money’ (32%) and ‘Cancer Diagnosis, Treatment and Survivorship’ (32%). Median overall QOL was 8 (range 3-10). Conclusions PROQOL is feasible for systematic capture of patient concerns in underserved, ethnic minority cancer patients. A better understanding of these concerns can help design interventions to improve psychosocial outcomes for the vulnerable groups and decrease disparities in care delivery.

Summary Improvement in survival in Light chain (AL) amyloidosis has been seen over recent decades, enabling more patients to achieve long‐term survival. Patients with AL amyloidosis who survived ≥10 years from time of diagnosis ( n = 186) were the subject of this study. Ten‐year survivors represented 22% of the total population. These patients were characterized by favourable patient, organ and plasma cell features. Of note, trisomies were less common among 10‐year survivors compared to those who did not survive to 10 years. All‐time best haematological response was complete response in 67%, very good partial response in 30%, partial response in 2% and no response in 1%, with 11% having received a consolidative strategy for inadequate response to first line therapy. The overall organ response rate to first‐line therapy was 76%, which increased to 86% when considering subsequent line(s) of therapy. Forty‐seven percent of the 10‐year survivors did not require a second‐line therapy. The median treatment‐free survival (TFS) among the 10‐year survivors was 10·5 years (interquartile range 7·4‐12·2). On multivariate analysis independent predictors for TFS were the achievement of complete haematological response and lack of cardiac involvement. Long‐term survivors are increasingly seen in AL amyloidosis and present distinct patient, organ and clonal disease features.

AbstractThe role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post‐transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression‐free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression‐free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression‐free survival for patients who achieve less than very good partial response.

Abstract In appropriately selected patients with AL amyloidosis, autologous stem cell transplant (ASCT) is an established treatment modality with excellent outcomes and decreasing transplant related mortality (TRM) over time. We report on 15‐year overall survival (OS) in 159 patients undergoing ASCT from 1996 to 2003, with median follow up of 17.1 years. Day 100 TRM was 13.2% (n = 21). The OS of ≥15 years was observed in 30% (47/159) of patients. Patients surviving ≥15 years were younger (53 vs 56 years, P = .02), less likely to have lambda as the involved light chain (62% vs 78%, P = .03) and were less likely to have heart involvement (32% vs 56%, P = .005). Median OS of patients with heart involvement vs not was 4.0 vs 11.1 years, P = .006 and actuarial 15‐year OS was 23% vs 43%, respectively. A higher proportion of patients with OS ≥15 years received full‐dose melphalan conditioning (81% vs 61%, P = .01), and achieved day 100 complete response (CR) (64% vs 24%, P < .001). Median OS amongst patients who achieved CR vs not was 19.3 vs 5.4 years, P < .001. Heart involvement, receiving full‐dose melphalan and achieving CR remained independent predictors of OS. AL amyloidosis and related complications were the cause of death in 52% of patients overall (1‐5 years post‐transplant: 81%; 5‐10 years: 62% and 10‐15 years: 55%). These results reinforce the key role of ASCT in AL amyloidosis. With improvements in TRM and more options for relapsed disease, we expect the long‐term survival post‐transplant to improve significantly in the future.

BackgroundThere exist insufficient data characterizing patients with multiple myeloma (MM) who experienced prolonged survival. A population‐based analysis of long‐term survivors was conducted to investigate the roles of sociodemographic factors and upfront stem cell transplantation (SCT).MethodsThe National Cancer Data Base is a US cancer database of approximately 34 million patients from >1500 cancer centers. Patients with MM were identified using the International Classification of Diseases for Oncology (ICD‐O) code 9732 from January 2004 to December 2006 and were divided into 4 groups based on overall survival (OS). Sociodemographic characteristics, treatment facility, and use of SCT were recorded. The univariate and multivariate analyses were performed using multiple logistic regression and Pearson chi‐square tests.ResultsA total of 26,986 patients with MM were identified. The median OS was 2.74 years. The majority of patients were male (54%), white (77%), insured (93%) and otherwise healthy (78%), lived in a metropolitan area (82%), were of high income (66%) and educational (58%) levels, and received treatment at nonacademic facilities (63%). Upfront SCT was used in 10% of patients. One in 6 patients (16%) were long‐term survivors (group 4). When comparing group 4 (OS of ≥8.22 years) with the other groups (OS of <8.22 years), young age, female sex, high income and educational levels, residence in a rural area, insured status, no comorbidity, receipt of upfront SCT, and treatment at high‐volume facilities were associated with long‐term survival.ConclusionsKey differences in sociodemographic characteristics, patient volume at treatment facilities, and upfront SCT were associated with long‐term survival. Improvements in health care access and health literacy, upfront SCT, and treatment at high‐volume facilities might prolong patient survival.

Abstract The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P &lt; .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.

Background:Venetoclax is a B cell lymphoma 2 (BCL‐2) inhibitor that has shown activity as a single agent and in combination with other therapies in patients with multiple myeloma, particularly those harboring t(11;14) associated with high BCL‐2 expression. Although early clinical trial data is encouraging (monotherapy response rate of 21% and 40% amongst t(11;14) and a response rate of 97% when used in combination with bortezomib and dexamethasone), data on outcomes in patients treated outside of clinical trial setting are sparse.Aims:We aimed to identify the efficacy of venetoclax in patients with multiple myeloma treated outside clinical trial.Methods:We conducted a retrospective review of all patients with multiple myeloma treated with venetoclax between December 2016 and February of 2019 at the Mayo Clinic outside of a clinical trial setting.Results:A total of 29 patients that were treated with venetoclax for relapsed or refractory multiple myeloma were identified. Characteristics of the cohort are reported in Table 1. Two thirds of the cohort had t(11;14) detected on cytogenetic studies and 48% (n = 14) had presence of high risk abnormalities. Median number of prior therapies was 6 (range 1–15) and 21% (n = 6) of patients had received ≥10 prior lines of therapy. Eighty three percent (n = 24) of patients had received prior autologous transplant and 76% (n = 22) were penta refractory or exposed. Median time from diagnosis of myeloma to initiation of venetoclax therapy was 5.3 years (range 0.8–23.6 years).Venetoclax used as monotherapy or a doublet in combination with dexamethasone in 59% (n = 17) of patients and a triplet or quadruplet in 41% (n = 12) given at 800 mg (55%) or 400 mg (35%) daily. Triplet and quadruplet regimens combined venetoclax with a variety of proteasome inhibitors or daratumumab. One patient had a quadruplet of venetoclax, carfilzomib, pomalidomide and dexamethasone. 93% (n = 27) patients were refractory to at least on proteasome inhibitor and immunomodulatory drug. Dose titration and escalation was used in 31% (n = 9) of patients. None of the patients experienced tumor lysis syndrome. At last follow‐up 55% (n = 16) of patients remain on venetoclax therapy. Overall response rate in the 24 patients evaluable for response was 46% (21% CR, 8% VGPR, 17% PR). Patients with t(11;14) had a numerically higher response rate than those without (50% vs 33%, p = 0.64). Patients with high risk cytogenetic abnormalities were less likely to respond (ORR 69% for standard risk vs 18% for high risk, p = 0.019). Median time to response was 2.6 months (range 1.1–6.9 months). Median duration of response was 5.2 months (range 2.2–12.9 months). After a median follow‐up time of 7.2 months for the cohort, the median PFS and OS are 5.8 and 14.6 months, respectively, Figure 1A/B. High risk cytogenetic abnormalities were associated with a shorter PFS (median PFS 3 months vs 14 months for standard risk, p = 0.002). The outcomes with venetoclax monotherapy and combination therapies are reported separately in the Table.Summary/Conclusion:Venetoclax is an effective oral agent in relapsed and/or refractory myeloma and can produce deep and durable responses in heavily pretreated patients. Further studies are needed to elucidate its role earlier in the disease and its effectiveness in combination with other anti‐myeloma therapies.image

Background:Previous literature has established “long‐term survivors” as patients who survive greater than 10 years from diagnosis of active multiple myeloma (MM). With the rapid discovery and evolving use of novel therapeutic agents, a greater proportion of patients are reaching this milestone. Although these patients share in their extended survival, they also constitute a heterogeneous group in terms of treatments and outcomes.Aims:The aim of this study is to examine a large cohort of long‐term survivors with protracted follow‐up as an attempt to identify a subset of patients within ten‐year survivors who have longstanding disease remission, and examine the predictors of their especially exceptional prognosis.Methods:All patients with active MM evaluated at Mayo Clinic, Rochester between January 1, 1999 and July 1, 2008 were included in the study. Patients with MGUS, smoldering MM, and solitary plasmacytoma were excluded. The overall survival (OS) was calculated from time of symptomatic disease requiring treatment. Patients with greater than 10 year survival from diagnosis were then divided into three cohorts based upon treatment and remission status: Cohort 1 included patients off therapy ≥ 5 years and in sustained remission, Cohort 2 included patients on maintenance therapy ≥ 5 years and in sustained remission, and Cohort 3 included patients who had relapsed within the past 5 years. Differences between the groups were compared using Wilcoxon, Chi‐square, and Fisher's exact test as applicable. “Early” stem cell transplant was defined as patients who received a stem cell transplant within one year of diagnosis.Results:During the time frame of the study, 2,125 patients were identified who fulfilled the diagnostic criteria for active MM. Three‐hundred ninety nine (19%) had survived at least 10 years from diagnosis. Among these patients, based on the available data regarding remission and ongoing treatment status, 332 patients were categorized into three cohorts, seen in Table 1. Sixty patients (18% of long‐term survivors) comprised Cohort 1, 48 patients (14% of long‐term survivors) comprised Cohort 2, and 224 patients (68% of long‐term survivors) comprised Cohort 3. Sex difference was statistically significant between the groups, with more females constituting Cohorts 1 and 2 (p = 0.03). Within Cohort 1, 77% of patients underwent an autologous stem cell transplant (ASCT). The median progression free survival following ASCT in this cohort was not reached (95% CI 15–NR, p < 0.001). In addition, patients in Cohort 1 and Cohort 2 were more likely to undergo an early ASCT as compared to patients in Cohort 3 (p = 0.002). There were no significant differences in high or intermediate risk FISH/cytogenetics at diagnosis, ISS at diagnosis, or induction therapies used at diagnosis among the three groups.Summary/Conclusion:Our study identified a small subset (3% of all patients diagnosed with active MM) of long‐term survivors who are off of therapy and remain in sustained longstanding remission. Female sex, progression free survival following ASCT, and receiving an early ASCT were factors that portended a positive prognosis amongst long term survivors.image