Rate Of Second Primary Malignancies Research Articles

Australians with chronic lymphocytic leukaemia continue to have high rates of second primary malignancies in the modern era.

Population-based studies have demonstrated a high risk of second cancers, especially of the skin, among patients with chronic lymphocytic leukaemia (CLL). We describe age-standardised incidence ratios (SIRs) of second primary malignancies (SPM) in Australian patients with relapsed/refractory CLL treated with at least two lines of therapy, including ibrutinib. From December 2014 to November 2017, 156 patients were identified from 13 sites enrolled in the Australasian Lymphoma and Related Diseases Registry, and 111 had follow-up data on rates of SPM. At 38.4 months from ibrutinib therapy commencement, 25% experienced any SPM. SIR for melanoma and all cancers (excluding nonmelanomatous skin cancers) were 15.8 (95% confidence interval (CI): 7.0-35.3) and 4.6 (95% CI: 3.1-6.9) respectively. These data highlight the importance of primary preventive interventions and surveillance, particularly as survival from CLL continues to improve.

Trends in Outcomes After Upfront Autologous Transplant for Multiple Myeloma Over Three Decades

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (P < .001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (P < .001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, P < .001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, P < .001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, P = .001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, P < .001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, P < .001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM undergoing upfront auto-SCT over the past three decades, including those with high-risk disease.

Salvage Autologous Transplant and Lenalidomide Maintenance Versus Continuous Lenalidomide/Dexamethasone for Relapsed Multiple Myeloma: Long Term Follow up Results of the Randomized GMMG Phase III Multicenter Trial Relapse

Introduction The randomized, controlled, multicenter, phase III GMMG ReLApsE trial compared lenalidomide/dexamethasone (Rd) re-induction, salvage high dose chemotherapy, autologous stem cell transplantation (HDCT/ASCT) and lenalidomide (R) maintenance with standard continuous Rd. We have previously reported the absence of a significant survival benefit in the primary analysis. However, landmark analyses from salvage HDCT performed due to the fact that ~30% of patients in the HDCT arm did not receive salvage HDCT/ASCT suggested a survival benefit in patients undergoing salvage HDCT/ASCT. Here we report long term follow up results from the GMMG ReLApsE trial. Methods Between 2010 and 2016, 282 patients were randomized of whom 277 constituted the intention-to-treat (ITT) population (arm B/A n=139/138). Arm B received 3 cycles of Rd (lenalidomide 25 mg, day 1-21; dexamethasone 40 mg, day 1, 8, 15, 22; 4 week cycles) re-induction, HDCT (melphalan 200 mg/m 2), ASCT and R maintenance (10 mg daily) until progression (PD). Arm A was treated with Rd until PD. Key inclusion criteria were 1-3 prior treatment lines, age ≤ 75 years, time to PD ≥ 12 months in case of front-line HDCT/ASCT and WHO PS ≤ 2. R-refractory disease was not permitted and only 30/277 patients (11%) were previously exposed to R. The primary endpoint was progression free survival (PFS). Protocol-specified long term follow up collection included overall survival (OS), further lines of treatment and further salvage HDCT/ASCT after trial participation. ISRCTN16345835, Eudra CT-No: 2009-013856-61. Results Within the extended follow up period of 99 months, 238 PFS events (86%) and 174 deaths (63%) occurred. Median PFS in the ITT population was 20.5 months in arm B and 19.3 months in arm A without a statistically significant difference (HR 0.98; 95% CI 0.76-1.27; p=0.9). Median OS was 67.1 months in arm B vs. 62.7 months in arm A (HR 0.89; 95% CI 0.66-1.20; p=0.44). The absence of a significant PFS and OS benefit was consistent among key disease subgroups according to age, R-ISS, renal function, frontline single vs. tandem HDCT/ASCT, prior lines of treatment and prior maintenance treatment post HDCT/ASCT. Time to progression after frontline HDCT/ASCT was significantly associated with PFS in the total ITT population (p=0.001) as well as in both trial arms independently, but was not associated with a survival benefit from arm B vs. A (interaction test PFS p=1.0, OS p=0.7). Multivariate analyses revealed significant associations of survival with age (PFS: HR 0.8, p=0.045), high risk cytogenetic aberrations (PFS: HR 2.1, p&amp;lt;0.001; OS: HR 2.5, p&amp;lt;0.001), ISS stage III vs. I (OS: HR 2.0, p=0.02), elevated LDH (PFS: HR 1.5, p=0.04; OS: HR 2.1, p&amp;lt;0.001), &amp;gt;1 prior lines of treatment (PFS: HR 2.3, p=0.003), and no prior HDCT/ASCT (PFS: HR 1.8, p=0.04; OS: HR 2.2, p=0.009), but not with treatment arm B vs. A (PFS: HR 0.9, p=0.4; OS: HR 0.9, p=0.37). In landmark analyses from HDCT and the contemporaneous Rd cycle 5 in arm A (median interval from randomization to HDCT/Rd cycle 5: 117/122 days; n=103[B]/114[A]) no significant differences in PFS (23.0 vs. 20.3 months; HR 0.91; 95% CI 0.68-1.22; p=0.52) or OS (76.3 vs. 66.0 months; HR 0.8; 95% CI 0.56-1.13; p=0.2) in arm B vs. A were observed. Further lines of treatment after trial participation were reported in 88/139 (63%) and 96/138 (70%) patients in arm B and A (p=0.31). Significantly more salvage HDCT/ASCT were administered after trial participation in arm A vs. B (48/138 [35%] vs. 19/139 [14%], p&amp;lt;0.001). Immunomodulatory drug (lenalidomide, pomalidomide) based regimens were used comparably after both trial arms. The rate of second primary malignancies was comparable in arm B and A (26/139 [19%] vs. 19/138 [14%], p=0.3). Conclusions The GMMG ReLApsE trial is the only randomized, controlled trial comparing salvage HDCT/ASCT with continuous novel agent treatment. With extended follow up, no significant PFS or OS difference is observed in the overall trial population and the previously reported survival benefit in patients who actually received salvage HDCT/ASCT is not confirmed. Time to progression after frontline HDCT/ASCT which is frequently used to stratify for salvage HDCT/ASCT in clinical practice is a general prognostic parameter for PFS, but does not predict benefit from salvage HDCT/ASCT vs. continuous Rd treatment. The GMMG ReLApsE trial does not support salvage HDCT/ASCT for relapsed or refractory multiple myeloma.

First-Line Venetoclax Combinations in Fit Patients with CLL: 4-Year Follow-up and NGS-Based MRD Analysis from the Phase 3 GAIA/CLL13 Trial

Background The primary endpoint analysis of the GAIA trial showed superior progression-free survival (PFS) and undetectable MRD (uMRD) rates for venetoclax-obinutuzumab (GV) and GV + ibrutinib (GIV) compared to chemoimmunotherapy (CIT) (Eichhorst et al., NEJM 2023). With additional follow-up, outcomes of the venetoclax (ven)-containing arms were compared and NGS-based MRD results were analyzed. Methods The phase 3 GAIA trial compared 3 different time-limited ven-based combinations against CIT in fit, treatment-naïve patients (pts) with CLL without TP53 aberrations. Pts were randomized to CIT (FCR ≤65 years; BR &amp;gt;65 years), GV, GIV or ven-rituximab (RV). In addition to MRD by flow cytometry (FCM), exploratory MRD analyses were performed using the amplicon-based EuroClonality NGS assay. Reported p values have a descriptive character. Results In total 926 pts were randomized (CIT: 229, RV: 237, GV: 229, GIV: 231). After a median observation time of 50.7 months (interquartile range 44.6-57.9), all pts are now off study treatment. PFS continued to be superior for GV and GIV compared to CIT (GV: median not reached [NR] vs 59.4 months; hazard ratio [HR] 0.47 [97.5% CI 0.32-0.69], p&amp;lt;0.001; GIV: NR vs 59.4 months, HR 0.30 [97.5% CI 0.19-0.47], p&amp;lt;0.001, Figure 1A). PFS with GV and GIV was also superior compared to RV (GV: NR vs 63.2 months; HR 0.57 [97.5% CI 0.38-0.84], p=0.001; GIV: NR vs 63.2 months, HR 0.38 [97.5% CI 0.24-0.59], p&amp;lt;0.001). PFS between GIV and GV was not significantly different (both NR, HR 0.63 [97.5% CI 0.39-1.02], p&amp;gt;0.025), however, GIV was associated with longer PFS compared to GV in pts with unmutated IGHV (HR 0.58 [95% CI 0.36-0.94]) but not in pts with mutated IGHV (HR 0.87 [95% CI 0.33-2.31]). Estimated 4-year PFS rates were 62.0% (CIT), 70.1% (RV), 81.8% (GV) and 85.5% (GIV). The estimated 4-year rates for time to next treatment were 77.2% (CIT), 86.2% (RV), 90.4% (GV) and 96.0% (GIV). Of the 111 pts with subsequent therapies for CLL-type progression (excluding 12 pts with treatment for Richter's transformation as second line), 60 (54.1%) received BTKi-based therapies, 30 (27.0%) ven-based treatments, 12 (10.8%) ven + BTKi and 5 (5.4%) CIT as second-line treatments. No differences in overall survival were observed between the treatment arms (4-year OS rates, CIT 93.5%; RV 96.2%; GV 95.1%; GIV 95.0%). In a multivariate analysis, unmutated IGHV (HR 2.86 [95% CI 1.64-5.01], p&amp;lt;0.001) and bulky disease (any lymph node ≥ 5 cm, HR 1.73 [95% CI 1.11-2.69], p=0.016) were independently associated with shorter PFS in the pooled GV/GIV arms. NGS-based MRD data in PB was available for 816 pts at month 15. Of these, 22.7% (52 pts, CIT), 23.6% (56 pts, RV), 60.3% (138 pts, GV) and 66.2% (153 pts, GIV) achieved uMRD &amp;lt;10 -6 (uMRD6, Figure 1B). In all treatment arms, PFS was shorter in pts with MRD ≥10 -6 compared to those with uMRD6 (CIT: HR 9.98 [95% CI 3.64-27.38], RV: HR 6.57 [95% CI 2.72-16.77], GV: HR 3.93 [95% CI 2.18-7.09], GIV: HR 2.10 [95% CI 1.03-4.28]). Pts who achieved uMRD below the conventional cut-off of 10 -4 by FCM but still had low levels of detectable MRD (≥10 -6 &amp; &amp;lt;10 -4) by NGS had shorter PFS than pts achieving uMRD6 in the pooled GV/GIV arms (HR 2.18 [95% CI 1.32-3.61], Figure 1C). A similar correlation was seen with CIT (HR 4.49 [95% CI 1.53-13.14]) and RV (HR 3.40 [95% CI 1.29-8.98]). In pts with uMRD6 at MO15, clinical response (partial/complete response) did not influence PFS. Grade ≥3 infections were highest in GIV and CIT (CIT: 45 pts [20.8%], RV: 27 [11.4%], GV: 34 [14.9%], GIV: 51 [22.1%]) and cardiac disorders most frequent with GIV (CIT: 14 pts [6.5%], RV: 19 [8.0%], GV: 18 [7.9%], GIV: 41 [17.7%]). Fatal adverse events occurred in 16 (7.4%, CIT), 8 (3.4%, RV), 9 (3.9%, GV) and 11 (4.8%, GIV) pts. The rate of second primary malignancies was higher with CIT (4.19/1000 patient-months) compared to RV (2.34), GV (2.39) and GIV (2.88). When excluding non-melanoma skin cancer, the incidence rates were 2.21 (CIT) 1.21 (RV), 1.16 (GV) and 2.36 (GIV). Conclusions With more than 4 years of follow-up, GV and GIV show superior PFS compared to CIT and RV. Pts with unmutated IGHV have longer PFS with GIV compared to GV. A majority of pts treated with time-limited GV or GIV (60.3% and 66.2%) achieves uMRD6 at MO15. NGS-based MRD assessment identifies pts with very long PFS and appears to improve prognostication in pts with uMRD &amp;lt;10 -4 by conventional FCM. Unmutated IGHV and bulky disease were independently associated with shorter PFS in pooled GV/GIV.

Second primary malignancies in patients with lymphoma in Denmark after high-dose chemotherapy and autologous haematopoietic stem-cell transplantation: a population-based, retrospective cohort study

Second primary malignancies (SPMs) are known complications after chemotherapy, but the risk is not well characterised for patients with lymphoma treated with high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the rate of SPMs in this population relative to matched control individuals from the general population. In this retrospective, population-based cohort study, patients aged 18 years or older with an aggressive lymphoma who received high-dose chemotherapy and autologous HSCT in Denmark between Jan 1, 2001, and Dec 31, 2017, were included from the Danish Lymphoma Registry and matched (1:5) to control individuals from the general population on birth year and sex via the Danish Civil Registration System. Patients were eligible if they had a registered date of autologous HSCT and patients with primary CNS lymphoma were excluded. Exclusion criteria for both patients and matched control individuals were HIV infection, organ transplantation, or other malignancies before inclusion. The key endpoint was the incidence of SPMs assessed in all study participants. The effect of treatment on SPMs was also investigated in patients who were followed up from first lymphoma diagnosis, with high-dose chemotherapy and autologous HSCT as a time-dependent exposure. Of 910 patients with lymphoma assessed, 803 were included (537 [67%] were male and 266 [33%] were female); 4015 matched control individuals were included (2685 [67%] were male and 1330 [33%] were female). Ethnicity data were not available. Median follow-up was 7·76 years (IQR 4·77-11·73). The SPM rate was higher among patients receiving high-dose chemotherapy and autologous HSCT than matched control individuals (adjusted hazard ratio [HR] 2·35, 95% CI 1·93-2·87, p<0·0001). Patients receiving high-dose chemotherapy and autologous HSCT had a higher rate of non-melanoma skin cancer (2·94, 2·10-4·11, p<0·0001) and of myelodysplastic syndrome or acute myeloid leukaemia (AML; 41·13, 15·77-107·30, p<0·0001) than matched control individuals, but there was no significant difference in the rate of solid tumours (1·21, 0·89-1·64, p=0·24). The cumulative risk of SPMs at 10 years was 20% (95% CI 17-23) in patients compared with 14% (13-15) in matched control individuals. High-dose chemotherapy and autologous HSCT was associated with an increased risk of SPMs when analysed as a time-dependent exposure from first lymphoma diagnosis (adjusted HR 1·58, 95% CI 1·14-2·17, p=0·0054). High-dose chemotherapy and autologous HSCT was associated with an increased risk of non-melanoma skin cancer and myelodysplastic syndrome or AML but not with increased risk of solid tumours in patients treated for lymphoma. These findings are relevant for future individualised risk-benefit assessments when choosing between high-dose chemotherapy and autologous HSCT and chimeric antigen receptor T-cell therapy in this setting. Danish Cancer Society.

Correlation between lymphoma and second primary malignant tumor.

Although studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated risk of lymphoma with different SPMs and risk factors related to different SPMs. We conducted a retrospective cohort study to evaluate the cumulative incidence and risk factors of different secondary SPMs in patients previously diagnosed as lymphoma, and to compare the survival rates of SPMs and primary malignant tumors. Retrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results database. Patients with an initial primary malignancy diagnosis of lymphoma between 2000 and 2019 were included in the study. The statistical analysis was conducted from March 2022 to January 2023. The development of an SPM defined as any type of malignant tumor 292,210 patients remained in final cohort, including 35,220 patients with secondary primary malignant tumor. The cumulative incidence of SPMs during 20 years of follow-up is 1.95% in combined respiratory system, 0.14% in central nervous system, is 0.82% hepatobiliary pancreatic system, is 1.31% in urinary system, is 1.92% digestive tract. Multivariate competitive risk model analysis showed that Different characteristics of lymphoma patients were associated with secondary different types of SPMS. The risk of secondary SPMs in lymphoma patients after radiotherapy and chemotherapy varies with the change of diagnosis time, diagnosis age and incubation period. Propensity score matching and Kaplan-Meier analysis showed that the survival rate of secondary tumor was significantly lower than that of matched primary malignant tumor. This study reminds us to consider the possibility of SPMs in the initial treatment of lymphoma patients, and develop a follow-up plan according to the characteristics of patients to reduce the risk of SPMs. Occurring more than 6 months after the diagnosis of lymphoma. The cumulative incidence of SPMs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the therapeutic factors associated risk for SPMs in patients undergoing radiotherapy or chemotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SPMs.

Five-Year Results and Overall Survival Update from the Phase 3 Randomized Study Augment: Lenalidomide Plus Rituximab (R2) Vs Rituximab Plus Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

Background: The combination of lenalidomide + rituximab (R2) showed superior efficacy vs rituximab + placebo (R-placebo) in patients (pts) with relapsed refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) (Leonard et al. J Clin Oncol 2019). Based on these AUGMENT study results, R2 was approved for the treatment of adult pts with previously treated follicular lymphoma (FL) or marginal zone lymphoma (MZL) in the US, Japan, and Brazil, and for FL in Europe. Reported here are updated long-term follow-up results from AUGMENT. Methods: AUGMENT (NCT01938001) is a multicenter, double-blind, randomized phase 3 study of R2 vs R-placebo (control) in pts with FL grade 1-3a or MZL who were previously treated with ≥ 1 prior systemic therapy with documented relapsed or refractory disease but not refractory to rituximab (refractory was defined as < partial response to rituximab or rituximab-chemotherapy OR disease progression < 6 mo after last rituximab dose). Pts were stratified by prior rituximab treatment (yes vs no), time since last antilymphoma therapy (≤ 2 vs > 2 y), and histology (FL vs MZL), and then randomized 1:1 to R2 or control for up to 1 y. R2 pts received oral lenalidomide 20 mg/d, d1-21/28 for 12 cycles plus rituximab IV 375 mg/m2 weekly in cycle 1 and d1 of cycles 2-5. Control pts received rituximab and placebo on the same schedule. Dose modifications were prespecified in the protocol to manage toxicities. The primary endpoint was progression-free survival (PFS) per 2007 IWG criteria without PET as assessed by Independent Review Committee (IRC; central review). During the follow-up period, pts were followed every 6 mo to assess endpoints, including overall survival (OS), time-to-next antilymphoma treatment (TTNLT), progression, second primary malignancies (SPMs), and histological transformation. Results: A total of 358 pts were randomized (n = 178 R2; n = 180 control); baseline characteristics were similar in both groups. As of January 26, 2022 at a median follow-up of 65.9 mo, median PFS per 2007 IWG criteria as assessed by Investigator was 27.6 mo for R2 vs 14.3 mo for control, with HR = 0.50 (95% CI, 0.38-0.66; P < 0.0001). Although median OS was not reached for either group, there was an improvement in OS for R2 (HR = 0.59, 95% CI, 0.37-0.95, P = 0.0285; Figure). 5-y OS rates for the R2 vs control groups were 83.2% (95% CI, 76.3-88.3) vs 77.3% (95% CI, 70.1-83.1). Median TTNLT (after 12 cycles of time-limited therapy) was 73.1 mo for R2 vs 31.8 mo for control with HR = 0.53 (95% CI, 0.39-0.71; P < 0.0001). In the R2 group, 73 pts (41%) received ≥ 1 subsequent antilymphoma treatment compared with 109 (61%) in the control group, most commonly rituximab in both groups (25% and 34%). 3 (2%) and 5 (3%) pts received lenalidomide as part of any subsequent anti-lymphoma treatment in the R2 and control groups, respectively. The updated overall safety profile of both groups was consistent with the 1st analysis. SPMs occurred in 13 (7%) R2-treated and 21 (12%) control pts, an increase from 6 (3%) and 10 (6%), respectively, in the previous analysis. 9 pts died of SPM (n = 3 R2, n = 6 R-placebo), an increase from 2 pts (both R-placebo) in the previous analysis. The incidence rate of SPMs per 100 y was 1.62 (95% CI, 0.94-2.78) in the R2 group vs 2.66 (95% CI, 1.73-4.07) in the control group. Fewer histological transformations occurred in the R2 arm than in the control group (n = 10 vs n = 15, respectively). The updated incidence rate of histological transformation in the overall population was 1.24% (95% CI, 0.66-2.3) in the R2 arm and 1.85% (95% CI, 1.12-3.07) in the control arm. Conclusions: R2 continues to demonstrate superior efficacy over rituximab monotherapy (plus placebo) as measured by the primary endpoint of PFS (as assessed by Investigator in long-term follow up). The updated results for OS are consistent with the improvement observed in PFS. The OS KM curve separation after 5 y continues to favor R2, providing evidence for a survival benefit. The updated TTNLT KM curves continue to demonstrate that fewer R2-treated patients needed subsequent antilymphoma treatment to date, well beyond the 1-y treatment period. The safety profile of R2 and R-placebo remain consistent with the primary analysis, with continued lower rates of SPM and rates of histologic transformation comparable to historical experience. These updated results, including OS data, provide further support for the use of the R2 regimen as a standard of care for pts with R/R iNHL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Mortality of Second Primary Malignancies after Lymphoma

Introduction: Treatment for lymphoma has undergone significant transformation in the past decade with the introduction of novel treatment strategies. Given the long-term treatment and supportive care, patients with lymphoma are living longer under better disease control, and patients with lymphoma are at increased risk of developing second primary malignancies (SPMs). Herein, we estimated the incidence, risk factors, and outcomes in lymphoma survivors with SPMs. Methods: Patients diagnosed with SPMs after primary lymphoma in Shandong Provincial Hospital (SPH) from 2010 to 2021 were included. Additionally, the differences in the incidence and characteristics of SPMs across ethnic groups were delineated by comparing with the Surveillance, Epidemiology, and End Results (SEER) database. We calculated the risk of SPMs using standardized incidence ratio (SIR) and absolute excess risk (AER). Overall survival (OS) analysis was reported using the Kaplan-Meier method. Results: A total of 2,912 hospitalized lymphoma cases were included, and 63 patients (2.16%) had SPM during the follow-up. Of these patients, 44 (69.84%) were male and 19 (30.16%) were female. The median age was 61 years old (range 35-81) and the majority of patients diagnosed with SPMs were older (≥60 years old, 61.90%) and previously treated with chemotherapy (69.84%). Histopathologic subtypes of primary lymphoma were as follows: (1) Hodgkin's lymphoma (HL, 3.17%), (2) non-Hodgkin lymphoma (NHL, 80.96%), and (3) Unknown type (15.87%). Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and diffuse large B-cell lymphoma (DLBCL) were the most common subtypes. The median duration between SPMs and lymphoma was 3.14 years (range 0-9). The most common types of SPMs were digestive system tumors (27, 42.86%), respiratory system tumors (13, 20.63%), and urinary system tumors (8, 12.70%). Specifically, the common types of SPMs were lung (19.6%), stomach (10.7%), and liver (8.9%) (Fig. 1). In addition, 304,696 new lymphoma cases are diagnosed, as reported to SEER 18 registries from 2010 through 2018, and 13580 survivors (4.46%) had SPMs. As described above, these patients with SPMs were also mostly male and older when diagnosed with SPMs. The commonly diagnosed SPMs are NHL (17.7%), lung and bronchus cancer (12.1%), and prostate cancer (10.0%). Additionally, we showed that the incidence rate of SPMs after specific lymphoma in the SEER database was higher than that of the SPH database other than CLL (Fig. 2). Because the crude incidence rate of SPM was not adjusted for the expected number of lymphoma or the number of high-risk patients in a reference population, the SIR and AER of SPM were calculated in the further analysis. Among patients at lymphoma diagnosis, overall malignancy risk was significantly higher than expected in the U.S. general population after follicular lymphoma (FL, SIR=2.01; 95%CI 1.93-2.09), marginal zone lymphoma (MZL, SIR=1.78; 95%CI 1.68-1.88), HL (SIR=1.76; 95%CI 1.62-1.91), CLL/SLL (SIR=1.51; 95%CI 1.46-1.57) and DLBCL (SIR=1.45; 95%CI 1.39-1.5). Moreover, hematological malignancies (SIR=3.23; 95%CI 3-3.48) contributed more to the SPMs than solid-organ cancers (SIR=1.31; 95%CI 1.226-1.27) among these subtypes. In a multivariate analysis, most patients with SPMs were diagnosed at younger ages (<55 years) and found to be other (Asian or Pacific Islander, American Indian/Alaska Native) races. Additionally, a higher mortality rate is associated with advanced age, no rituximab-based chemotherapy, and latency (P<0.05). We found that OS is shorter for patients with SPMs compared with those without SPMs, with increasing divergence over time (P<0.00001). In further analysis, we compared the survival of the most common SPMs in people who were diagnosed with specific lymphoma. The results showed that lymphoma patients with NHL, urinary bladder, stomach, and lung cancer experienced worse survival compared with melanoma, thyroid, kidney, and breast cancer (P<0.00001). Conclusion: Our study illustrated the incidence, mortality, and related risk factors of SPMs in specific lymphoma survivors and showed that the incidence of SPMs after the lymphoma is higher in older men, particularly in lung cancer. We found an increased risk for lymphoma compared to the general population. More studies are needed to understand the molecular underpinning leading to increased SPM formation in lymphoma patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk of colon cancer-related death in people who had cancer in the past.

The rate of second primary malignancies (SPM) is gradually increasing. Yet, the risk of death from primary cancer vs. SPM is still not well understood. In this study, we investigated the survival of patients with colorectal cancer (as SPM) who had cancer in the past (prior cancer) and the risk factors of SPM death in this population. Based on the Surveillance, Epidemiology, and End Results (SEER) database, we identified 1866 colon cancer patients with prior cancer in our main cohort and 43,959 colon cancer patients, including 37,440 patients with colon cancer as only malignancy and 6519 patients with colon cancer as subsequent colon cancer (SCC), in a second cohort and 3429 colon cancer patients, including 2371 patients with prior colon cancer (PCC) and 1058 patients with colon cancer as SPM, in a third cohort. After propensity score matching, 6519 pairs of subjects were identified in second cohort. Patients with prior prostate and breast cancer had a higher risk of developing colon cancer compared to those with gastrointestinal cancer. Also, colon cancer patients with different prior cancer had different survival rates. Furthermore, except for prior lung cancer (52.78 vs. 25.93%), most subjects died due to colon cancer complications. The ratio of colon cancer deaths to prior cancer deaths in patients with a low stage and high stage was 1.51 and 6.64, respectively. In addition, colon cancer-specific survival (CSS) and OS rates were significantly lower in subjects with colon cancer as the SPM than in those with PCC. Also, compared with PCC, SPM was associated with OS and CSS with HR 1.59 (95 CI 1.43-1.78) and HR 2.00 (95% CI 1.70-2.36). Furthermore, compared with only colon cancer, SCC was associated with OS and CSS with HR 1.23 (95 CI 1.17-1.29) and HR 1.13 (95% CI 1.06-1.21). Prior cancer was found to have an adverse impact on OS in patients with colon cancer (secondary cancer), most of whom died due to colon cancer as secondary cancer itself rather than prior cancer. Early detection and treatment strategies should be investigated in this population.

Development of second primary malignancies after transoral surgery in human papilloma virus-positive oropharyngeal squamous cell carcinoma.

Little data exists regarding the incidence of oropharyngeal and upper aerodigestive tract (UADT) second primary malignancies (SPM) among human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here we evaluate SPM rates among patients with HPV-related OPSCC. A retrospective cohort study of 412 patients with HPV-related OPSCC who underwent transoral resection +/- adjuvant therapy at a single center between 1996 and 2018. Twenty patients (4.9%) developed SPM of the UADT, nine (2.2%) occurring in the oropharynx. Median time to diagnosis was 59.5months (0-173 months). Risk of SPM was lower for patients receiving adjuvant radiation (aHR: 0.25, 95%CI: 0.08-0.78). There was no difference in overall or disease-free survival between those with and without SPM. The rate of SPM among patients with HPV-positive OPSCC is lower than reported rates among HPV-negative OPSCC. To date, this is the largest study evaluating SPM in patients with surgically treated HPV-positive OPSCC.

Abstract PD10-06: Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study

Abstract Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS]) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p&amp;lt;0.001). Compared to mBRCA2 breast cancer pts, those with mBRCA1 were younger, more likely to have reported Jewish ancestry, had more grade 3 tumors, less nodal involvement, lobular histology and HER2 positivity, and received more frequently chemotherapy (all p&amp;lt;0.001). More mBRCA1 pts with hormone receptor-positive tumors did not receive adjuvant endocrine therapy (14.7% vs. 4.2%, p&amp;lt;0.001). No difference between mBRCA1 and mBRCA2 pts was observed in risk-reducing mastectomy (43.9% vs. 46.0%; p=0.371) or salpingo-oophorectomy (48.3% vs. 48.8%; p=1.0). Median follow-up was 7.9 years (range 5.6-10.6 years). Second primary breast cancers (17.0% vs. 12.2%, p=0.025) and non-breast primary malignancies (4.3% vs. 1.9%, p=0.033) were more frequent among mBRCA1 pts compared to mBRCA2 pts, while distant recurrences were less frequent (10.4% vs. 15.4%, p=0.013). 8-year DFS was 62.8% and 65.9% for mBRCA1 and mBRCA2 pts, respectively (adjusted HR 0.76; 95% CI 0.60-0.96). The worse DFS in mBRCA1 was observed regardless of hormone receptor status (pinteraction=0.848): hormone receptor-positive (adjusted HR 0.77; 95% CI 0.58-1.03) and hormone receptor-negative (adjusted HR 0.73; 95% CI 0.48-1.13). No differences in DRFI and OS were observed between mBRCA1 and mBRCA2 pts. Compared to pts with hormone receptor-negative disease, those with hormone receptor-positive breast cancer had higher chances of developing distant (± loco-regional) recurrences (16.1% vs. 9.0%; p&amp;lt;0.001) and less frequent second primary malignancies (BC: 12.1% vs. 17.9%, p=0.005; non-BC: 2.8% vs. 4.0%, p=0.216). No differences in DFS and OS were observed between pts with hormone receptor-positive or negative breast cancer. However, there was a trend towards worse DRFI in women with hormone receptor-positive breast cancer as compared to those with hormone receptor-negative disease (8-year DRFI: 83.4% vs. 90.1%; adjusted HR 1.39; 95% CI 0.94-2.05). Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.

Second Primary Malignancy after Acute Promyelocytic Leukemia: A Population-Based Study.

Simple SummaryAcute promyelocytic leukemia (APL) is a rare and aggressive subtype of acute myeloid leukemia (AML). Since the introduction of all-trans-retinoic acid (ATRA) in APL management, the survival rate has increased substantially. However, there is evidence that retinoids might enhance tumor growth and the risk of secondary malignancies. The relationship between secondary cancer risk and APL treatment that includes ATRA is incompletely characterized. In this study, we investigated the risk factors associated with second primary malignancies after treatment of APL. Age ≥ 40 years at diagnosis of APL was significantly associated with an increased risk of second malignancies. Our findings suggest a potential carcinogenic role for ATRA in the salivary gland, liver, and soft tissue malignancies. Moreover, secondary tumors were significantly more frequent among patients with primary APL than in individuals with non-APL malignancies. Our finding suggests opportunities for surveillance for patients who completed treatment for APL.Acute promyelocytic leukemia (APL), is now highly curable with treatment approaches that include all-trans retinoic acid (ATRA). The high incidence of APL in the Hispanics suggests an association with genetic variants in this population. Information on second primary malignancies (SPMs) in patients with APL is limited. The Surveillance, Epidemiology, and End Results (SEER) database was used to interrogate whether the rate of SPMs in patients with APL was associated with ethnicity and/or ATRA treatment. Between 2000 and 2016, 116 cases of SPM were diagnosed among 4019 patients with APL. The mean age at diagnosis of primary APL was 53.9 years (±15.7 years), and the mean age at diagnosis of SPMs was 59.0 years (±14.5 years). Comparisons with 3774 APL survivors who did not develop SPMs revealed that age ≥40 years at diagnosis of APL (p < 0.001) and non-Hispanic white ethnicity (p = 0.025) were associated with SPMs in APL survivors. Salivary gland, liver, and soft tissue malignancies were significantly more common in patients with primary APL than in individuals with non-APL malignancies. A risk analysis comparing patients who had APL with patients who had non-APL AML suggests that SPMs after APL is associated with ATRA treatment. Therefore, patient follow-up after APL should focus on early diagnosis of SPMs.

Second cancer incidence in CLL patients receiving BTK inhibitors

Chronic lymphocytic leukemia (CLL) is associated with perturbed immune function and increased risk for second primary malignancies (SPM). Ibrutinib and acalabrutinib (BTKi) are effective therapies for CLL resulting in partial restoration of immune function. The incidence of and risk factors for SPM in CLL patients receiving BTKi are not yet characterized. We retrospectively determined the incidence of SPM in CLL patients treated with ibrutinib or acalabrutinib at our institution between 2009 and 2017, assessed for association between baseline characteristics and SPM incidence, and compared the observed to expected cancer incidence among age, sex, and year matched controls without CLL. After a median of 44 months follow-up, 64/691 patients (9%) were diagnosed with SPM (excluding non-melanoma skin cancer [NMSC]). The three-year cumulative incidence rate was 16% for NMSC and 7% for other SPM. On multivariable analysis, smoking was associated with increased SPM risk (HR 2.8 [95% CI: 1.6–4.8]) and higher baseline CD8 count was associated with lower SPM risk (HR 0.9 for 2-fold increase [95% CI: 0.8–0.9]). The observed over expected rate of SPM was 2.2 [95% CI: 1.7–2.9]. CLL patients treated with BTKi remain at increased risk for SPM, and secondary cancer detection is an important consideration in this population.

Increasing Incidence of B-Cell Non-Hodgkin Lymphoma and Occurrence of Second Primary Malignancies in South Korea: 10-Year Follow-up Using the Korean National Health Information Database.

PurposeThe epidemiology of B-cell non-Hodgkin lymphoma (BNHL) in Asia is not well described, and rates of second primary malignancies (SPM) in these patients are not known. We aimed to describe temporal changes in BNHL epidemiology and SPM incidence in Korea.Materials and MethodsA retrospective cohort study used claims data from the National Health Insurance Service that provides universal healthcare coverage in Korea. Newly diagnosed patients aged at least 19 years with a confirmed diagnosis of one of six BNHL subtypes (diffuse large cell B-cell lymphoma [DLBCL], small lymphocytic and chronic lymphocytic [CLL/SLL], follicular lymphoma [FL], mantle cell lymphoma [MCL], marginal zone lymphoma [MZL], and lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia [WM]) during the period 2006-2015 were enrolled and followed up until death, dis-enrolment, or study end, whichever occurred first. Patients with pre-existing primary cancers prior to the diagnosis of BNHL were excluded. ResultsA total of 19,500 patients with newly diagnosed BNHL were identified out of 27,866 with non-Hodgkin lymphoma (NHL). DLBCL was the most frequently diagnosed subtype (41.9%-48.4% of NHL patients annually, 2011-2015). Standardized incidence of the six subtypes studied per 100,000 population increased from 5.74 in 2011 to 6.96 in 2015, with most increases in DLBCL, FL, and MZL. The incidence (95% confidence interval) of SPM per 100 person-years was 2.74 (2.26-3.29) for CLL/SLL, 2.43 (1.57-3.58) for MCL, 2.41 (2.10-2.76) for MZL, 2.23 (2.07-2.40) for DLBCL, 1.97 (1.61-2.38) for FL, and 1.41 (0.69-2.59) for WM. ConclusionBNHL has been increasingly diagnosed in Korea. High rates of SPM highlight the need for continued close monitoring to ensure early diagnosis and treatment.

Overall survival and second primary malignancies in men with metastatic prostate cancer.

BackgroundAmong prostate cancer (PC) patients, over 90% of distant metastases occur in the bone. PC treatments may be associated with side effects, including second primary malignancies (SPM). There is limited information on the incidence of SPM among men with bone metastatic PC (mPC) and among men with bone metastatic castration-resistant PC (mCRPC). We estimated overall survival and the incidence of SPM in men with mPC and mCRPC.MethodsIn the Prostate Cancer data Base Sweden, the National Prostate Cancer Register was linked to other national health care registers, 15,953 men with mPC in 1999–2011 were identified. Further, 693 men with mCRPC were identified. Outcomes were evaluated using stratified incidence rates, Kaplan-Meier estimators and Cox models.ResultsThe mean age among men with mPC was 73.9 years and in men with mCRPC 70.0 years. The median respective survivals were 1.5 (13,965 deaths) and 1.14 years (599 deaths), and average times since PC diagnosis 1.8 and 4.7 years. We observed 2,669 SPMs in men with mPC and 100 SPMs in men with mCRPC. The incidence rate of SPM per 1,000 person-years was 81.8 (78.8–85.0) for mPC and 115.6 (95.1–140.7) for mCRPC. High age, prior neoplasms, urinary tract infection, congestive heart failure, diabetes and renal disease were most strongly associated with increased mortality risk. Prior neoplasms and prior use of antineoplastic agents were most strongly associated with increased SPM risk. Several factors associated with increased mortality and SPM risks were more prevalent in the mCRPC cohort.ConclusionsOur results on mortality for men with mPC and mCRPC are in line with previous studies from the same time period. Investigation of factors associated with mortality and SPM in men with mPC and mCRPC can help to further understand these outcomes in the era prior to several new treatments have come available.

PF486 THE IMPACT OF PRIOR MALIGNANCIES ON THE DEVELOPMENT OF SECOND MALIGNANCIES AND SURVIVAL IN PATIENTS WITH FOLLICULAR LYMPHOMA: A NATIONWIDE POPULATION‐BASED STUDY IN THE NETHERLANDS

Background:Advances in the treatment of follicular lymphoma (FL) have considerably improved survival in FL. This success, however, might come at price, as FL patients correspondingly life long enough to potentially develop second primary malignancies (SPMs). A prior study among multiple myeloma (MM) factorpatients showed that a prior malignancy diagnosis (PMD) 3/4 as potential proxy for genetic susceptibility to cancer 3/4 was associated with SPM development and mortality after MM diagnosis (Jonsdottir, Blood Adv, 2017). At present, information on the impact of a PMD on the development of a SPM and mortality in FL is lacking.Aims:The aim of this nationwide population‐based study was to assess the impact of a PMD on the development of a SPM and survival in patients with FL in the Netherlands.Methods:We selected all adult FL patients diagnosed between 1994–2012 from the Netherlands Cancer Registry (NCR). PMDs and SPMs (excluding basal cell carcinoma) relative to FL were identified from the NCR and classified into subgroups as per the third edition of the International Classification of Diseases for Oncology (Fig 1A). Synchronous malignancies diagnosed within a time‐interval of 6 months prior to or after FL diagnosis (n = 300) were excluded. We used competing risk regression as per Fine and Gray 3/4 with death as a competing risk 3/4 to estimate sub‐distribution hazard ratios (SHRs) with 95% CIs for the association between a PMD before FL diagnosis and the development of a first SPM after FL diagnosis. These associations were also calculated for subgroups of SPMs. Cox regression was used to calculate hazard ratios (HRs) with 95% CIs to assess the risk of death associated with a PMD. All patients were followed from date of FL diagnosis to date of first SPM, death, or end of follow‐up (February 1, 2017). We adjusted all analyses for baseline characteristics at FL diagnosis (i.e. sex, year of diagnosis, age, and disease stage). Further, we examined the effect of additional adjustment for anti‐neoplastic therapy of PMDs and FL treatment started within one year after diagnosis (chemotherapy, radiotherapy only, no therapy, other therapy) on the effect estimates for a PMD. A P &lt; 0.05 indicated statistical significance.Results:We included 9,251 patients, of whom 672 (8.1%) had ≥1 PMD. At a median follow‐up of 6.9 years (range &lt;0.1–23.0), patients with a PMD developed a SPM more often than patients without a PMD (23% v 15%; P &lt; 0.001). Further, patients with a PMD were older at FL diagnosis (median age, 70 v 60 years; P &lt; 0.001) and more often female (50% v 42%; P &lt; 0.001). Overall, a PMD was associated with an increased rate of a SPM (Fig 1B), with an adjusted SHR of 1.67 (95% CI 1.39–2.00; P &lt; 0.001). This association was statistically significant for the following subgroups of SPMs: breast‐ and lung cancer and melanomas and squamous cell carcinomas of the skin (P &lt; 0.05). Further, a PMD was associated with an increased risk of death (adjusted HR, 1.19; 95% CI, 1.07–1.33; P &lt; 0.001). The increased rate of SPMs and risk of death associated with a PMD was irrespective of the type of therapy applied for PMDs or FL, as additional adjustment for these factors did not affect the effect estimates.Summary/Conclusion:We demonstrated an association between a PMD and the development of a SPM and survival among patients with FL. Since additional adjustment for therapy did not alter the direction or magnitude of these associations, our results might suggest a role for genetic susceptibility to cancer. We encourage future studies to corroborate on the association between a PMD and SPM development in FL.image

PS1462 SECOND PRIMARY MALIGNANCIES IN MYELOFIBROSIS PATIENTS TREATED WITH RUXOLITINIB: REAL WORLD EVIDENCE FROM 215 CONSECUTIVELY TREATED PATIENTS IN LOMBARDY

Background:Patients with myeloproliferative neoplasms (MPNs) have a higher risk than the general population of developing a lymphoid neoplasm (Rumi et al, Haematologica 2011). It is still unclear whether this holds true for non‐hematological second primary malignancies (SPMs) (Frederiksen et al, Blood 2011; Susini et al, Blood 2012). However, among 20,250 MPN patients included in the Surveillance, Epidemiology, and End Results Program (SEER) database, the 10‐year cumulative incidence of SPMs was 12.7%, significantly higher than that expected in the general U.S. population (Brunner et al, Leuk Lymphoma 2016). Ruxolitinib (RUX) is an oral JAK1/2 inhibitor approved for the treatment of myelofibrosis (MF). Recently, Porpaczy et al (Blood 2018) alerted on the possible risk of aggressive lymphomas developing in MPN patients treated with JAK inhibitors including RUX, even though patient selection bias complicates interpretation.Aims:To assess SPM occurrence in RUX‐treated MF patients on the basis of real world data (RWD) provided by the health authority of Regione Lombardia, complemented with institutional data.Methods:Lombardy, a region of roughly 10 million individuals, has a well‐established network for hematology (Rete Ematologica Lombarda, REL), with a specific commission for MPNs. Within the REL we conducted an ambispective observational study (RUXOREL‐MF) including all MF patients treated with RUX, i.e. 215 subjects regularly followed at 17 centers. The study was approved by the Review Board of each Institution and conducted in accordance with the Declaration of Helsinki. Incidence rates were computed from the number of events versus the time at risk after RUX start. Time‐to‐event analyses used Kaplan‐Meier estimators, log‐rank tests and cause‐specific Cox models based on time elapsed after RUX start.Results:Main patient characteristics according to SPM (excluding non‐melanoma skin cancer, NMSC) occurrence are summarized in Table 1. Median follow up from diagnosis of MF was 61.5 months (interquartile range, IQR, 34.1–97.3). Median follow up from RUX start was 24.2 months (IQR 12.6–40.4). Forty‐nine (22.8%) patients died, two due to the SPM. Median overall survival from RUX start was 78.7 months. 27 cases of SPMs were reported prior to RUX start, with no case of lymphoma. 24 cases of SPMs occurred after RUX start (lung, 1; breast, 3; prostate, 2; bladder, 1; melanoma, 1; multiple myeloma, 1; NMSC, 13; other, 2). The incidence rate of SPMs post‐RUX was 4.3 per 100 pt‐years (95% CI 2.7–6.5), whereas it was 1.7 per 100 pt‐years (95% CI 0.8–3.2), when excluding NMSCs from the analysis. Median time to SPM diagnosis after RUX start was 16.9 months (IQR 6.9–21.5) and 19.8 months (IQR 16.3–36.7) when excluding NMSCs. Cumulative incidence of SPMs (excluding NMSCs) after RUX start is reported in Fig. 1. Patients with a SPM pre‐RUX were at higher risk of developing a SPM post‐RUX (HR 3.6, 95% CI 1.1–11.0, p = 0.02). Significance was lost if the analysis excluded NMSC (HR 3.8, 95% CI 0.8–18.7, p = 0.08).Summary/Conclusion:Our RWD offer a unique opportunity to provide real world evidence on the incidence of SPMs in MF patients receiving RUX. In our cohort no case of lymphoma was registered with a median follow up after RUX start matching the median time to lymphoma occurrence reported in the aforementioned publication. Incidence of SPMs after RUX start was 4.3 per 100 pt‐years and 1.7 per 100 pt‐years when excluding NMSC. A matched control study including MF patients not receiving RUX is ongoing and will be presented at the EHA meeting.image

Primary Treatment of T1-T2 Hypopharyngeal Cancer: Changing Paradigms.

There has been a general shift in the treatment of hypopharyngeal cancer from open surgical techniques (either radical or partial "organ" preserving) toward non-surgi cal "organ preserving" strategies (radiotherapy [RT] or chemoradiotherapy [CRT]) and minimally invasive transoral laser microsurgery (TLM) or transoral robotic surgery (TORS). Oncologic outcomes reported are comparable whatever modality is chosen, but better functional outcomes are observed in the RT/CRT and TLM/TORS-treated patients. Because of the high rate of second primary malignancies, which influences overall survival, one could favor an up-front transoral surgical procedure as a primary treatment modality for early hypoharyngeal carcinoma, leaving the (chemo)radiotherapeutic option open for treatment of a likely later emerging second primary. However, the TLM and TORS studies report a high rate of adjuvant irradiation-based treatment for close or positive margin excisions. Concerning post-treatment functionality, both RT/CRT and TLM/TORS yield satisfactory results, especially when compared to the open surgical procedures, but it remains unclear which of these options will result in the long-term best laryngopharyngeal functional outcome. There is a need for multi-institutional randomized controlled trials comparing the long term oncologic and functional outcomes of up-front minimal invasive transoral surgery with/without adjuvant treatment, to a primary non-surgical organ preservation treatment.

Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial

Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial

B-cell acute lymphoblastic leukemia (B-ALL) in CLL patients treated with lenalidomide.

7531Background: The immunomodulatory drug lenalidomide (len) has shown clinical activity in CLL. It has been associated with an increased rate of second primary malignancies (SPM) in multiple myelo...